Reactions of Aldehydes and Ketones and their Derivatives · water, through both bulk and speciﬁc...

CHAPTER 1

Reactions of Aldehydes and Ketones and their Derivatives

B. A. MURRAY

Department of Applied Sciences, Institute of Technology Tallaght, Dublin, Ireland

Formation and Reactions of Acetals and Related Species . . . . . . . . . . . . . . . 1Reactions of Glucosides and Nucleosides . . . . . . . . . . . . . . . . . . . . . . . . . . . 3Reactions of Ketenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4Formation and Reactions of Nitrogen Derivatives . . . . . . . . . . . . . . . . . . . . 5

Imines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5Iminium Ions and Related Species . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8Oximes, Hydrazones, and Related Species . . . . . . . . . . . . . . . . . . . . . . . . . 8

C−C Bond Formation and Fission: Aldol and Related Reactions . . . . . . . . . 10Regio-, Enantio-, and Diastereo-selective Aldol Reactions . . . . . . . . . . . . . . . 10The Mukaiyama Aldol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11Other Aldol-type Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12Allylations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

Other Addition Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15General and Theoretical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15Protonation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16Hydration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16Addition of Zinc Reagents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17Addition of Other Organometallics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18The Wittig Reaction, and Variants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19Addition of Other Carbon Nucleophiles . . . . . . . . . . . . . . . . . . . . . . . . . . . 22Miscellaneous Additions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

Enolization and Related Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25Enolates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

Oxidation and Reduction of Carbonyl Compounds . . . . . . . . . . . . . . . . . . . 27Oxidation Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27Regio-, Enantio-, and Diastereo-selective Reductions . . . . . . . . . . . . . . . . . . 28Other Reduction Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

Atmospheric Chemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32Other Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

Formation and Reactions of Acetals and Related Species

A simple hemiacetal has been stabilized by pressure.1 Acetone and propanol react togive 2,2-dimethoxypropane: if the reaction is carried out with 1 : 1 dilute reactantsin THF, the hemiacetal is formed quantitatively at pressures above 2 GPa (20 atm).

Organic Reaction Mechanisms 2000. Edited by A. C. Knipe 2004 John Wiley & Sons, Ltd ISBN 0-470-85439-1

1

2 Organic Reaction Mechanisms 2000

All thermodynamic functions have been reported for the reaction, as functions oftemperature and pressure.

3-(Hydroxymethyl)-5-methylsalicylaldehyde (1, or its acetonide) undergoes a stereo-selective cyclotetramerization to yield the S4-symmetric (R,S,R,S)-tetraacetal (2), themost thermodynamically stable of the four possible diastereomers.2 �de

OHOH

Me

H

O

MeO

O

OO

MeO

O

OO

H

HH

H

Me

Me

(2)

(1)

9-Phenyl-1-thia-5-oxaspiro[5.5]undecane, a spiro-1,3-oxathiane prepared from 4-phenylcyclohexanone and 3-mercaptopropan-1-ol, exists as a mixture of diastereomers,(3-cis) and (3-trans), with the phenyl acting as a ‘holding group’ on the cyclohexanering.3 Rate and equilibrium data have been reported for the isomerization in CDCl3solution via an open-chain form, i.e. a ring–chain tautomeric equilibrium.

O

S

S

O

Ph Ph(3-cis) (3-trans)

Formaldehyde acetals, R1OCH2OR2, are increasingly employed as fuel additives.Their fate in the atmosphere has been investigated in studies of the rate of reactionwith hydroxyl radicals.4 They show higher reactivity than ethers or alcohols, with themain degradation pathway being initiated by OH attack at the α-carbon of one orother R group.

The relative rates of hydrolysis of a range of aldehyde- and ketone-derived acetals,orthoesters, and orthocarbonates have been compared with each other and with therelated six-membered cyclic and six, six-membered spiro analogues, with a view toseparating out steric, inductive, and stereoelectronic effects.5

The roles of solvent, catalyst, and sonication have been studied in the acetalizationof D-gluconolactones with long-chain aldehydes.6

For selective hydrolysis of hydrazones without affecting acetals, see Hydrazonesbelow.

1 Reactions of Aldehydes and Ketones and their Derivatives 3

Reactions of Glucosides and Nucleosides

Many alcohols which can be chemically glycosylated do not react in the β-glucosidase-mediated enzymatic reaction. A computation approach correlates the reactivity of thealcohol (in the enzymatic case) with its nucleophilicity: the charge on the reactingatom is an excellent predictor.7a Using a simplified model of the enzyme active site,transition-state energies have been calculated in two cases. Cyclohexanol, a typi-cal ‘reacting’ alcohol, was found to have an activation energy of 1.3 kcal mol−1,whereas that of phenol (‘non-reacting’) is calculated to be 15.8 kcal mol−1. In termsof charge, the reacting alcohol with the lowest calculated charge (benzyl alcohol)is ca 0.1 electrons more charged than the non-reacting case with the highest charge(p-methoxyphenol). In substantiation of this predictive method, three alcohols whichwere calculated to be reactive were found to be so, contrary to results of a previousstudy.7b

N -Acetylxylosamidoxime (4) has been synthesized: it is intended to use it andderivatives thereof as transition-state analogues for glycosyltransferases specific toN -acetylglucosamines.8

HN

NHAc

NO

H

OBn

OBn

(4)

A range of glycosyl transfer reactions designed to favour intramolecular (1,x)-shifts (x = 3,4,5,9) proceed via intermolecular pathways only.9 Stereocontrolled gly-cosyl transfer reactions, using unprotected glycosyl donors, have been reviewed (87references).10

The kinetics and mechanism of reaction of bromo- and chloro-malonaldehydeswith adenosine in aqueous solution have been studied.11 Such aldehydes are known toarise intracellularly from mutagenic bifunctional halo compounds. The etheno prod-ucts that they yield with nucleobases are also useful tools in nucleic acid chemistry,owing to their fluorescence and, in some cases, the survival of the formyl functionfor further derivatization. The reactions proceed through the attack of the exo-aminogroup of adenine on the carbonyl carbon, and there are relatively small differencesbetween the chloro and bromo reactants, or between the malonaldehydes and themore-studied acetaldehydes. The most efficient conditions for formation of the ethenoproduct (formed via a deformylation) and of the formyletheno product are described.

In a theoretical study of proton transfer in the mutarotation of sugars, 2-tetrahydro-pyranol was chosen as a model sugar. The rate-limiting step of ring opening has beenstudied for two mechanisms: a high-energy intramolecular proton transfer and a low-energy route using formic acid as catalyst.12 The latter process is a double protontransfer reaction, concerted but asynchronous.


The kinetics and mechanism of spontaneous β-glycoside hydrolysis has been inves-tigated for a series of deoxy- and deoxyfluoro-2,4-dinitrophenyl-β-D-glycopyrano-sides.13 Within this series, field effects on the O(5) substituent (i.e. the site of chargedevelopment in the transition state) dominate: Hammett ρI values vary from −2.2to −8.3 in the glucoside series, for example. Inter-series comparisons also involvevariations in steric and solvation effects.

The kinetics of the acetolysis of methyl 2,3,4,6-tetra-O-acetyl-D-mannopyranosidescatalysed by sulfuric acid have been reported for acetic anhydride/acid solution.14

Other reports describe a regioselective α-phosphorylation of aldoses in aqueoussolution,15 phosphorylation of D-aldo-hexoses and -pentoses with inorganic cyclotri-phosphate,16 and a 1,2-trans stereoselective allylation of 1,2-O-isopropylidene-protec- �de

ted glycofuranosides.17 Intramolecular O-glycoside bond formation has been reviewed(95 references).18

Reactions of Ketenes

An ab initio study of the gas-phase reaction of hydroxyl radical with ketene indi-cates three distinct mechanisms: (i) direct hydrogen abstraction to give water andketenyl (HCCO), a channel which dominates at high temperatures; (ii) olefinic carbonaddition; and (iii) carbonyl carbon addition.19 The results compare well with suchexperimental data as are available, and the implications for atmospheric combustionprocesses are discussed.

Preparation of ketene (5), by Wolff rearrangement from 4-diazo-3-isochromanone,shows direct kinetic evidence for a non-carbene route.20

O

C

O

(5)

A theoretical study of ketene and its thio and seleno analogues suggests that all arebest represented by neutral cumulene structures, that the latter two are more reactive, andthat the thioketene is closer in behaviour to the seleno compound than the oxo case.21

Carbon suboxide (O=C=C=C=O) is calculated to hydrate at the C=C bond,22

in contrast to hydration of ketene, where addition to C=O to give the 1,1-enediolis favoured.

Methyl trimethylsilylketene acetals have been oxidized with urea–hydrogen perox-ide to yield α-siloxy esters, using catalytic methyltrioxorhenium; treatment with KFthen gives the corresponding α-hydroxy esters.23

Mechanisms of 2 + 2-cycloaddition of ketenimine (H2C=C=NH) and imine(H2C=NH) have been studied theoretically,24 and the chemistry of α-oxoketenethioacetals has been reviewed (28 references).25


Formation and Reactions of Nitrogen Derivatives

Imines

A computational study of the addition of HCN to methanimine in the gas phase andin aqueous solution has been employed to assess the feasibility of a prebiotic Streckersynthesis of glycine from formaldehyde, hydrogen cyanide, ammonia, and water in theprimitive atmosphere.26 High reaction barriers appear to rule out the process in the gasphase (and hence in interstellar space?), but these barriers are lowered substantially inwater, through both bulk and specific solvation effects on zwitterionic transition states.

In one of many stereoselective imine reactions reported, Strecker addition of tri-methylsilyl cyanide to chiral imines derived from 1-phenylethylamine usually proceedswith modest de. Higher diastereoselectivity has been achieved with a chiral β-diamine: �de

NMR evidence suggests an autocatalytic effect.27

Kinetic resolutions of two important ring systems, 3-substituted indanones and 4-substituted tetralones, have been achieved with ees/des of over 90% via an asymmetric �eehydrosilylation of their N -alkylimines.28

Lithium anions of chiral alkyl p-tolyl sulfoxides add to (S)-N -benzylidene-p-toluenesulfonamides to give enantiomerically pure β-(N -sulfinyl)amino sulfoxides, �de

and ultimately optically pure β-amino alcohols, via a stereoselective Pummererreaction.29

Enantiopure imines, derived from reaction of (R)- or (S)-α-methylbenzylamine witha ketone, have been reduced to amines in high de, using zinc borohydride.30 Imineshave been condensed diastereoselectively with ester enolates.31 The stereochemistry �de

of addition of dialkyl and diaryl phosphites to 1,4-phenylene Schiff bases has beenstudied.32

Several reactions with organometallic reagents are described. Diethylzinc hasbeen added enantioselectively to diphenylphosphinoylaryl-33 and alkyl-imines,34

�eeR−CH=N−P(=O)Ph2(R = Ar, alkyl), using chiral amino alcohols as auxiliaries.Electron-deficient N -sulfonylimines undergo α-substitution with organometallicbases.35 As part of a study of the BF3-mediated addition of lithium phenylacetylide(Ph−C≡C−Li) to an imine, BF3 · R3N adducts have been found to be usefulsubstitutes for boron trifluoride etherate.36 Alkyllithiums and alkyl Grignards havebeen added asymmetrically to 3-methoxynaphthalen-2-ylimines (6) as part of a route �eetowards chiral 2-substituted tetralones.37 1-Benzyltetrazolylimine undergoes additionof an alkyl Grignard to give an N -alkyl product (i.e. azophilic addition), whereas the2-benzyl analogue predominantly reacts at carbon, a contrast explained in terms offrontier orbitals.38 New unsymmetrical diamines have been prepared39 by addition ofGrignards to a chiral bisimine (S,S-7).

Several reports deal with imines as intermediates. Ethyl (Z)-N -(2-amino-1,2-di-cyanovinyl)formimidate (8) reacts with carbonyl compounds under basic conditions toform a Schiff base. The range of subsequent reactions to give a variety of heterocyclicsystems has been investigated.40 Pictet–Spengler combination of dopamine with D-glyceraldehyde under biomimetic conditions is accelerated by transition metal cations,apparently by activating Schiff base intermediates.41 The reaction of benzaldehydewith phenylhydroxylamine apparently proceeds via a hydrogen-bonded pre-association


NR

OMe

N N

PhPh

H

Me

HMe

(S, S-7)

N

H2N

CN

CN

OEtH

(8)(6)

complex involving the planar portion of each, an effect not seen in the stericallyhindered cases of 2,6-dichlorobenzaldehyde and norcamphor.42

In the reaction of hydroxymethanesulfonate (HOCH2SO3−) with anilines, the anion

is found to dissociate to formaldehyde and sulfite; the formaldehyde then forms acarbinolamine with the aniline, which dehydrates.43 Subsequent reaction with thefree sulfite gives the product, an anilinomethanesulfonate (ArNHCH2SO3

−). Kineticstudies in the pH range 1–8 indicate a change in rate-determining step (from carbino-lamine formation to its dehydration), the analysis requiring consideration of sideequilibria, such as that producing the dianion, −OCH2SO3

−.In another Mannich-type reaction, a face-specific intramolecular ring closure of an

aldehyde has been reported.44 The origin of diastereoselectivity in vinylogous Mannich �de

reactions has been studied theoretically.45

The carcinogenic action of benzidene (9) may proceed via peroxidase oxidationto bisimine (10). The latter has been investigated, together with its equilibria tomono- (10 · H+) and di-cationic (10 · H2

2+) forms, with pKas found to be 9.0 and5.0, respectively.46 These are in stark contrast to its monophenylene analogue (p-benzoquinone diimine), for which the corresponding values are 5.75 and < 1.5. TheN ,N -dimethyl derivative of (9) has also been studied: its two-electron oxidation prod-uct is confined to mono- and di-cationic forms only, and has coincidentally the samepKa (5.0) for their interconversion. The cations survive for minutes to hours, reactingwith water eventually, with the monocation surprisingly more reactive. The mono-cation can be considered, via resonance, to be an amino-stabilized nitrenium ion, butis ca 109 times longer-lived than simple 4-biphenylylnitrenium ions.

(10)(9)

H2N NH2 HN NH

H2N+ +NH2 H2N+ NH

[O]

(10 H+)(10 H22+) ••


α,β-Ethylenic imines undergo tautomerization to secondary enamines and Michaeladdition with electrophilic alkenes.47 1,3-Oxazolidines can be prepared by reactingimines with epoxides, catalysed by samarium(II) or -(III) iodide.48

The chemistry of imines, enamines, and oximes, and in particular their syntheticapplications, have been reviewed49a (231 references) for the years 1997 and 1998,continuing the coverage of an earlier review.49b N -Functionally substituted iminesof polychlorinated and polybrominated aldehydes and ketones have been reviewed(198 references): groups attached to the nitrogen include acyl, oxycarbonyl, car-bamoyl, sulfonyl, and phosphoryl.50 Addition of electron-deficient alkenes to 2,4,6-cycloheptatrien-1-imines has been the subject of a short review.51

The cycloaddition of benzylidenebenzylamine (PhCH=NPh) to 5-norbornene-2,3-dicarboxylic acid unexpectedly yielded the tricycle (11), together with its aroma-tized analogue.52 The mechanism of the reaction, which was carried out in THFwith boron trifluoride catalysis, was established by reacting the imine with 2,3-dihydrofuran. Other ring formations described include the mechanism of cycliza-tion of 2-ethynylbenzaldehyde derivatives (imines and O-methyloximes) to yieldisoquinolines,53 the kinetics of cyclocondensation of arylimines with thioglycolic acidto yield 4-thiazolidinones,54 and a carbonylative 5 + 1-cycloaddition of α-cyclopropy-limines to yield α,δ-unsaturated six-membered lactams.55

A range of activated, sterically strained N -arylsulfonyl-p-quinone mono- and di-imines undergo several unusual reactions not observed for their unstrained analogues.56

An investigation of the Biginelli dihydropyrimidine synthesis from a benzaldehydeand a urea suggests that recent claims of a ‘non-thermal microwave effect’ on rates andyields are not substantiated.57 Microwaves have no beneficial effect on this reactionover conventional heating at the same temperature. Higher rates can be producedat high pressure, but this is due to the higher temperatures achievable (and, in thisreaction, high pressure also causes a diversion to other products). Acceleration andgreater yield were found only under ‘open’ conditions, where superheating is notthe critical issue: rather, rapid solvent boil-off produces near-solvent-free conditionsand the removal of condensate water. This conclusion is reinforced by near-replicateresults achieved with conventional, rapid, evaporative heating.

The kinetics of condensation of anilines with 4-methyl-5-phenyl-2,3-dihydrofuran-2,3-dione have been described.58

A pH–rate profile has been constructed for the hydrolysis of H2salen [N ,N ′-bis(salicylidene)ethylenediamine] in aqueous methanol.59 Ce(III), Ce(IV), Cu(II), andZn(II) ions retard the rate of hydrolysis, apparently through the formation of tri-cyclic chelates.

(11) (12)

NH

O

Ph

H

H

N+

R2 R2

R1

R1 O−


Iminium Ions and Related Species

(S)-1-Alkyl-2-hydroxy-1,2,3,4-tetrahydroisoquinolines have been prepared by catalyticasymmetric addition of dialkylzincs to 3,4-dihydroisoquinoline N -oxides (12), using �eean (R,R)-tartrate auxiliary.60

α-Aryl-N -phenylnitrones, R−CH=N+(−O−)−Ph, undergo additions with silylketene acetals.61 The reactions are catalysed by lanthanide triflates, catalysts that arewater-soluble, recoverable, and reusable.

Neighbouring group participation effects, with a carbonyl as neighbour, have beeninvestigated in the dehydrogenation of 2-(1-piperidinyl)-benzaldehydes and -aceto-phenones.62

A protonated Schiff base derived from β-ionone has been studied using moleculardynamics.63

The recent chemistry of N -acyliminium ions has been reviewed, with a particularemphasis on their use in C−C bond formation, both inter- and intra-molecular.64

Oximes, Hydrazones, and Related Species

As a demonstration of C−C bond formation under mild aqueous conditions, ethylradicals have been added to a range of C=N functions. Four types of glyoxylic iminederivatives were studied: oximes, oxime ethers, and hydrazones (R1O2CCH=NR2,R2 = OH, OBn, NPh2 respectively), and nitrones [R1O2CCH=N+(O−)Bn]. All butthe oximes added an ethyl group to the imino-carbon in good to quantitative yield,and often taking only 10 min.65 The authors also report a stereocontrolled version in �de

the case of an oxime ether (R1 = Me, R2 = OBn).66

Formation of oximes from pyruvic acid (MeCOCO2H) involves rate-determining �eedehydration of the carbinolamine intermediate under acidic and neutral conditions.67

Addition of hydroxylamine to 9-formylfluorene (13) yields a carbinolamine adduct,and ultimately the oxime.68 Rate and equilibrium constants are reported for theseand related reactions in aqueous solution (pH 4–12), with reaction via protonatedcarbinolamine implicated at high acidity. Derived values for the pKa for the O-protonation of the aldehyde (−4.5), and for the C-protonation of its enol tautomer(−5.7) are also reported.

2-Acetylpyridinephenylhydrazone (14) has been found to be particularly resistant tohydrolysis in acid, with the onset of an A-SE2 process only occurring in 0.6 mol dm−3

H2SO4, followed by a changeover to A2 above 6.0 mol dm−3.69 This is not merelybecause the pyridine nitrogen acts as a ‘siren effect’ protonation site for the catalyst,but also because the proton further stabilizes the syn conformer of the −N(1)−C−C−N(2)− group of (15). As (15) is hydrolysis resistant, a further protonation is requiredto disrupt the dominance of the syn structure.

A new synthesis of gem-dichlorostyrenes (17) has been reported: unsubstitutedhydrazones of benzaldehydes (16) react with carbon tetrachloride, with copper(I)catalysis.70 The mechanism, although complex, appears to involve (i) oxidation ofCu+ by CCl4, producing dichlorocarbene, (ii) oxidation of (16) by Cu2+, to givethe corresponding phenyldiazomethane, and (iii) combination of the diazo and car-bene intermediates to give (17) plus N2, with evolution of the latter facilitating the


(13)

H

O

(15)(14)

N2

N3H

Me N1

N2

N3H

Me N1

H+

(18)

(17)

R

N NH2

H

R

H

RN

H

R

N

H

Cl

Cl

(16)

CuCl, CCl4

aq. NH3

(+ N2)

monitoring of the kinetic behaviour. Electron-donating substituents divert the reactionin favour of azine (18), via diazo self-combination.

Fluorinated β-diketones, F3C−CO−CH2−COR, react with aryl (or heteroaryl)hydrazines to give a range of pyrazole and �2-pyrazoline derivatives.71 Semiem-pirical calculations suggest that the product balance is determined by dehydration of3,5-dihydroxypyrazolidine intermediates, under kinetic control.

De-aromatized dienylimines (19, syn- and anti-) have been claimed as intermedi-ates in the Fischer indolization of ortho-substituted N -trifluoroacetyl enehydrazines(20; R = Me, OMe; n = 1, 2).72

Addition of carbon nucleophiles to aldehyde tosylhydrazones of aromatic and het-eroaromatic compounds can lead to alkylative reduction or alkylative fragmentation,both potentially synthetically useful.73

(20)(19)

N NH

NCOCF3

(CH2)nR

(CH2)n

H

H

R


A chiral 3-amino-2-oxazolidinone has been employed in a highly stereoselectivealkylation of hydrazones derived from propanal and from benzaldehyde, in up to 98%de.74 �de

For ketone hydrazones containing acetal functionality, ammonium dihydrogenphos-phate buffers selectively hydrolyse the hydrazone.75

General and specific acid catalysis of hydrazone formation from salicylaldehydeand phenylhydrazine have been observed in aqueous ethanol.76

Solvent effects on the formation of thiosemicarbazides have been studied.77

For an oxime transition-state analogue for glycosyltransferases, see Glucosides above.

C−C Bond Formation and Fission: Aldol and Related Reactions

Regio-, Enantio-, and Diastereo-selective Aldol Reactions

Non-linear effects in asymmetric catalysis have been reviewed.78 While the topic is ofwide general relevance, the over-arching importance of enantio- and diastereo-selectiveC−C bond-forming reactions merits its mention here. When an enantioselectivereaction is carried out with an impure chiral catalyst, the ‘normal’ expectation is thatthe selectivity will be linearly related to the purity, i.e. that eeproduct increases linearly �eewith eecatalyst. However, significant non-linear effects, both positive and negative, areincreasingly being reported: the review includes 26 references, and several other paperscovered in this chapter highlight positive effects in particular. Many cases appear toderive from autocatalytic effects. The authors describe the use of non-linear behaviour,and especially the kinetics of such reactions, for identifying active catalytic species andoverall mechanism. Examples are included of trade-offs between product enantiopurityand the extent of conversion. The area holds considerable promise for the design ofmore efficient and more enantioselective catalytic systems.

Other notable trends in aldolizations and elsewhere in this chapter include con-tinuing growth in the use of lanthanide Lewis catalysts and the expansion of greenchemistry, particularly the use of wholly or substantially aqueous solvent systems.

Several reviews cover aldols specifically. The development of an asymmetric aldoli-zation using enoxytrichlorosilane reagents (i.e. trichlorosilane enolates) and chiralphosphoramide Lewis bases has been reviewed (26 references).79 The strategy of �eeusing Lewis bases as catalysts (as opposed to the more familiar acids) is discussed, asare the mechanistic insights achieved to date. The review follows a similar conferencereport.80 Other accounts review asymmetric aldols of fluorocarbonyl compounds (41references),81 and the asymmetric addition of isocyano carboxylates to aldehydes (31references).82

An enantioselective reaction between 2-trimethylsilyloxyfuran (21) and aldehydesin the presence of a BINOL–titanium(IV) complex (BINOL = 1, 1′-binaphthol) hasbeen claimed as the first autocatalytic, asymmetric, autoinductive aldol reaction.83

�eeThe dianionic species PhCH(Li)CMe2C(OLi)=CH2 [derived from reductive

cleavage of a methylene oxetane (22)], undergoes regioselective aldol reactions withaldehydes and ketones.84 The same authors report the preparation of a lactone fromreaction of a radical enolate [derived from 2-methylene-3-phenyloxetane (23)] withthe enolate of acetaldehyde.85


(22)(21) (23)

OMe3SiO O OPh Ph

Diastereo- and enantio-selective aldol reactions have been carried out using tita- �de

nium(IV) alkoxides undergoing ligand exchange with added α-hydroxy acids suchas mandelic acid.86 The mandelic acid binds through its alcohol oxygen, and theexchange process seems to be critical: simple carboxylic acids will not work, nor will �eepreformed complexes made from titanium tetraalkoxide and an α-hydroxy acid.

Theoretical and experimental investigations of intramolecular aldol condensationsof 1,6-diketones and their bis(acylsilane) analogues, [Me3SiCOCH2CH2−]2, showno evidence for spontaneous cyclization, despite an apparently low barrier for thecyclization step itself.87,88

Proline has been found to catalyse a model aldol reaction, that between acetoneand p-nitrobenzaldehyde, in good yield and up to 76% ee, with 96% ee achievable �eein the case of isobutyraldehyde.89 The synthesis does not require inert conditions orprior deprotonation or silylation, and the non-toxic catalyst can be extracted easily.An enamine route is proposed.

Other selective aldol reactions include one dependent on the enolization of chiralα-silyloxy ketones by dicyclohexylchloroborane,90 a chiral diazaborolidine-mediated �de

enantioselective aldol reaction of phenylthioacetate ester,91 and a catalytic, enantio-selective homo-aldol reaction of ethyl pyruvate (MeCOCO2Et).92 A solvent effect on �eethe product outcome of an aldol reaction is described.93

The Mukaiyama Aldol

The Mukaiyama aldol methodology has been reviewed (128 references).94

Amphiphilic calix[6]arenes (24; R = Bu, Hx) are efficient surfactants for a Mukai-yama aldol reaction of silyl enol ethers with aldehydes in water, with scandium(III) �de

triflate catalysis.95 The alkyl groups on the lower rim appear to stabilize the silyl

(24)

CH2

OR

SO3Na

6


enol ether in a hydrophobic environment; they also promote the aldol reaction, asevidenced by its complete failure if R = H.

A novel lead(II) catalyst system, employing a BINOL–crown ether and Pb(OTf)2,catalyses aldol reactions of benzaldehyde and silyl enol ethers in aqueous solution,with ca 50% de and ee.96 �de

�ee

Using a chiral zirconium catalyst in a Mukaiyama-type aldol reaction, high anti-selectivity has been achieved (up to 93%), with ees up to 99%, in a convenient reaction �eeat 0 ◦C.97 The zirconium–BINOL catalyst requires an alcohol as a protic additive, for

�deturnover purposes.A rhodium(I)-catalysed asymmetric reductive aldol reaction of benzaldehyde and

various acrylate esters has been reported.98 Employing a BINAP (1, 1′-binaphthalene) �eeauxiliary with methyldiethylsilane at ambient temperature, the method provides analternative to the Mukaiyama aldol reaction.

A highly nucleophilic phosphine, tris(2,4,6-trimethoxyphenyl)phosphine, catalysesthe aldol reaction between ketene silyl acetals and aldehydes, apparently through a �de

‘naked enolate’ intermediate.99

Trichlorosilyl enolates derived from methyl ketones are competent aldol reagents, �de

reacting with aldehydes at ambient temperature without additives.100 Chiral phospho-ramides accelerate the additions and raise the ee substantially (or the de, where either �eepartner bears a stereogenic centre, in ‘matched’ cases).

Other Aldol-type Reactions

Two reviews cover the nitro-aldol reaction: one deals with catalytic asymmetric aspects(48 references)101 and the other assesses the current state of development of diastereo-selectivity in this reaction, and its potential for onward synthesis of nitro-, amino-, and �eeimino-polyols (51 references).102 Tandem nitroaldol–dehydration reactions have beencarried out between phenylsulfonylnitromethane dianion, LiO2N=C(Li)−SO2Ph, andaldehydes.103 The β,γ -unsaturated α-nitrosulfone products are found to equilibrate �de

with their α,β-unsaturated isomers at neutral pH.α-Bromoacetonitrile undergoes a samarium(II)-mediated nitrile aldol with aliphatic

aldehydes and ketones, to yield β-hydroxynitriles; addition of tetra(n-hexyl)ammoniumbromide enhances the diastereoselectivity.104

�de

The vinologous aldol reaction has been reviewed (229 references),105 with particularemphasis on its silyloxy diene version.

α,β-Unsaturated ketones (25) have been cross-coupled with aldehydes in aproticsolvents using chromium dichloride.106 The product cyclopropanols (27) are proposedto arise from the formation of a ketone α,β-dianion (26) equivalent, which reacts withthe aldehyde at the α-position (i.e. aldol), followed by intermolecular cyclopropan-ation. The stereoselectivity of the reaction and its implication for the mechanism arealso discussed.

The diastereoselectivity of the aldol reaction of aldehydes with the C(3) carbanionof a 1,3-dihydro-2H -benzodiazepin-2-one (28) has been investigated at −78 ◦C.107

�de


(25) (27)(26)

O

R

O

R

OH

R′OH

R

' '

R′CHO2 Cr(II) −

−

(29)(28)

N

N

MeO

Cl

3N

N

N

S

OH

C

NH2

MeH

HO

2a

A diastereoselective intramolecular Michael–aldol reaction has been exploited �de

under kinetic and thermodynamic conditions; the menthyl auxiliary employed allowscomplete control of four stereogenic centres at −78 ◦C.108 γ -Nitro ketones are formedby the reaction of tin enolates with α-nitroalkenes, and tetrabutylammonium halidesstrongly accelerate the reaction.109 Cyanoalkenes can be substituted as Michaelacceptor, to give γ -cyano ketones. �de

Mentions of the Baylis–Hillman reaction include titanium tetrachloride-mediatedexamples without the direct use of a Lewis base,110 a mild asymmetric reaction usingtributylphosphine and a chiral binaphthol as cooperative catalysts,111 and a novel �eecamphor-based auxiliary which gives 94–98% de in the synthesis of β-hydroxy-α-

�demethylene carbonyl derivatives.112

The decomposition pathways of 2-(1-hydroxybenzyl)thiamine (29), an adduct ofbenzaldehyde with thiamine and a reactive intermediate in the thiamine-catalysedbenzoin condensation, have been investigated via a kinetic study of an N1′-benzylatedmodel compound.113 Buffers catalyse the first step, the removal of the C(2α) proton,i.e. that which is originally derived from benzaldehyde.

The self-condensation of indan-1,3-dione has been reinvestigated, to determinethe structures of the minor products.114 In an asymmetric pinacol coupling of aro- �eematic aldehydes, a non-linear temperature effect on the stereoselectivity has been

�deexploited.115

The Claisen–Schmidt condensation of benzaldehyde and acetophenone yields theenone, PhCH=CHCOPh. Following computational studies of the progress of thereaction for a series of para-substituted benzaldehydes,116 a new mechanism is pro-posed to explain the observed kinetics.


A mild and efficient Reformatsky-type coupling of an α-bromo ester and a rangeof aldehydes and ketones produces β-hydroxy esters in good yields; intramolecularexamples are included.117 Samarium(II) iodide mediates an asymmetric Reformatskyreaction of chiral α-bromoacetyl-2-oxazolidinones with aldehydes, in up to 99% de.118

�de

Allylations

Bis(allyl)silanes (30, 31) with convergent silicons are highly efficient allylating agentsin the presence of fluoride ion.119 19F NMR evidence is presented for chelation offluoride as a central feature of the catalysis, and reactions with a range of aldehydes aredemonstrated. With appropriate bis-functionalized silanes, the strategy can be extendedto allenylation and alkynylation of carbonyls.

(31)(30)

Si

Si

Si

Si

1,3-cis-Disubstituted methylenecyclohexanes have been prepared with high regio-and stereo-selectivity via TiCl4-promoted addition of 1,5-dienylallylsilanes to aliphatic �de

aldehydes, followed by cyclization.120

Catalytic, enantioselective allylation of aldehydes with chlorosilanes and chiral �eephosphoramide Lewis bases has been shown to be an example of asymmetric ampli-fication via a positive non-linear effect.121 Kinetic studies show that the origin of thisbehaviour lies in the presence of two phosphoramide ligands in the stereochemicallydetermining transition state and in the rate-determining step.

Maruoka and co-workers’ suggestion that allylstannations of aldehydes catalysedby B(C6F5)3 owe their selectivity to hypercoordination at boron122a –c is challenged byan investigation, supported by X-ray and 19F NMR studies, that suggests tin chelationas the more likely explanation.122d

Chemo-, regio-, and stereo-selectivity have been achieved in the allylation of alde-hydes in aqueous organic solution, by hydrostannylation of allenes using PdCl2 · �de

(PPh3)2 –HCl–SnCl2, apparently via in situ formation of allyltrichlorotin inter-mediates.123

A short review considers the enantio- and diastereo-selective addition of allyltin �eereagents to aldehydes and imines.124 Aldehydes have been allylated regio- and dias-tereo-selectively by pre-complexing the allyl reactant with a molybdenum centre.125

�de

A steroidal aldehyde has been converted to the corresponding homoallylic alcohol inhigh yield and de, using triflic acid as catalyst for addition of allyltributylsilane in anaqueous medium.126 Ytterbium trichloride has been employed to catalyse allylation ofaromatic and aliphatic aldehydes by allyltrimethylsilane.127


Other Addition Reactions

General and Theoretical

Equilibrium constants for reaction of boron trifluoride etherate with carbonyl com-pounds to form complexes, >C=OBF3, have been reported for CDCl3 solution.128

The value for benzaldehyde is 0.208, and ρ+ for substituted benzaldehydes is −2.0.Reactions involving complexation to cyclohexanone and isobutyraldehyde are alsoreported, and the implications of the results for Lewis acid-catalysed addition to alde-hydes are discussed.

Facial selectivity in nucleophilic addition to the dioxa cage ketone (32) is low,whereas its trioxa analogue (33) reacts with a high preference for anti attack.129

The factors involved have been studied by a computational approach, and have beenextended to carbene addition to related alkenes.

(33)(32)

OO

O

OO

O

O

A detailed kinetic study of π -facial selectivity in conformationally rigid ketoneshas been undertaken.130 Using 5-substituted adamantan-2-ones (34) and trans-10- �de

substituted decal-2-ones (35), the balance of axial versus equatorial attack in C-methylation has been monitored kinetically for eight different organometallic pro-tocols. Current theories of π -facial selection do not seem to explain the results: whileaxial reactivities increase monotonically with the electronegativity of X, keq shows amore subtle dependence on the conformation of the X group, and on reaction condi-tions.

(34)

O

X

X

O

(35)

O

O

SMe

SMe

(36)

‘Soft’ nucleophiles such as methanol or aziridine add across the centralolefinic bond of 6,7-bis(methylsulfonyl)-1,4-dihydro-1,4-methanonaphthalene-5,8-dione (36).131 However, ‘hard’ species such as sulfinates or cyanide add across thebenzoquinone system to give hydroquinonoid products. In one case, the ambidentnucleophile benzenesulfinate, a mechanistic switchover occurs on changing from


DMSO to dimethoxyethane solvent, with the latter softening the nucleophile and thuspromoting S-addition at the olefinic site.

Protonation

The mechanisms of enantioselective protonation of silyl enol ethers and ketene disilylacetals by Lewis acid-assisted chiral Brønsted acids, to give α-aryl ketones and α-arylcarboxylic acids, respectively, have been investigated using density functional theorycalculations.132 Examples include tin tetrachloride and optically active binaphthol usedstoichiometrically, as well as stoichiometric 2,6-dimethylphenol with catalytic amountsof BINOL monomethyl ether, two methodologies which lead to high ees. �ee

A series of crowded dialkylphenyl ketones, 2, 6-diR1−C6H3−CO−R2, have beenprotonated in the gas phase and in sulfuric acid.133 The gas-phase basicity changeslittle with such substitution, apparently because the bulkiness and the polarizability ofthe R1 and R2 groups cancel out. In solution, however, a variation of 8 pK units isobserved, with steric inhibition of the solvation of the protonated carbonyl emergingas the major effect, unless strong conjugative interactions are present.

Protonation equilibria of substituted benzaldehydes have been calculated for the gasphase and for a solvation model.134

Hydration

The kinetics of hydration of three o-quinone methides (37a–c) have been studiedin aqueous solution in the pH range 0–8.135 The product o-hydroxybenzyl alco-hol was also used as precursor in each case, with the methide being generated byphotodehydration, and its reaction being monitored by the loss of absorbance at 400nm. An acid-catalysed arm in the rate profile gives way to a pH-independent regionfrom ca pH 4 onwards. From deuterium isotope effects and other considerations, themechanisms are

1. pre-equilibrium O-protonation, followed by reaction of the cation with water (inthe acid case); and

(37a) (37b) (37c)

H

O O O

OMe


2. nucleophilic attack of water at the methylene to give a (probably short-lived)zwitterion, followed by inter-oxygen proton transfer (in the pH-independent case).

While saturation of the acid catalysis was not reached for the simple methide (37a),its benzylidene analogue (37b) and its p-methoxyphenyl derivative (37c) did levelout at around pH 0.

‘No barrier’ theory has been used to calculate rate constants for hydration of awide range of carbonyl functions, from formaldehyde to carboxamides, for whichexperimental data are also available; agreement within 1–2 kcal mol−1 for �G �= wasobtained.136 The method allows rate constants to be calculated from equilibria, andvice versa. Results for hydroxide catalysis were particularly good, while in the caseof uncatalysed hydration, the cyclic versus non-cyclic mechanisms are not as yetresolved, although the cyclic mechanism is supported for difficult additions. Similarcalculations using multi-dimensional Marcus theory are also reported.137

The thermodynamics of the addition of water and alcohols to the carbonyl group of1-vinyl-2-formylimidazole, and to its conjugate acid, have been studied spectroscopi-cally, and compared with the corresponding equilibria in several related representativeheterocyclic compounds.138

Addition of Zinc Reagents

Most reports detailed enantioselective addition of diethylzinc to benzaldehyde, oftenfeaturing non-linear effects (see also the introduction to the Aldol and Related Reac-tions section above). For example, positive non-linear effects allow enantio-impurecatalysts to give higher reaction ees than their own ee. To push ees higher, a strategy �eehas been developed in which a diastereomeric catalyst is bound by a chiral substrateanalogue so as to inactivate one diastereomeric form.139 In suitable cases, the relative �de

turnover frequencies of the diastereomers can be manipulated to give enhanced enan-tioselectivity for the catalysed reaction, i.e. a catalytic system which ‘self-inhibits’ the‘wrong’ reaction. The strategy is demonstrated for the ethylation of benzaldehyde.

In two other examples, chiral catalysts such as o-hydroxybenzylamines140 and o-hydroxyaryldiazaphosphonamides141 give positive non-linear effects in the ethylation �eeof aromatic aldehydes. The former uses the hydroxyl to ‘steer’ the zinc and the latterinvolves a monomer–dimer equilibrium in the action of the catalyst. A modest non-linear effect is reported for a C2-symmetric ligand with four chiral centres.142

An integrated ab initio plus molecular mechanics procedure (‘IMOMM’) givesan excellent correlation with experiment in predicting the enantioselectivity of addi-tion promoted by (R)-2-piperidino-1,1,2-triphenylethanol (38). The non-transferredethyl group appears to play a crucial role in transferring stereochemical informa-tion from ligand to reaction centre, suggesting that the computationally convenientdimethylzinc that is often employed in calculations is an inappropriate model for itsdiethyl analogue.143 Three (−)-fenchyl alcohol derivatives, characterized by X-raycrystallography, give fair to good ees when used as pre-catalysts.144 The results are �eerationalized via computations on the ‘transferring’ and passive alkyl groups aroundthe zinc.


N

PhOH

Ph

Ph

(38)

A kinetic and calorimetric study involving a (morpholino)isoborneol auxiliary showssignificant product inhibition occurring.145 The alcoholate of the product binds rever- �eesibly, which may be important in setting the balance between conversion and enan-tioselectivity in diethylzinc reactions.

Among several other enantioselective diethylzinc additions,146 – 149 a δ-amino alco-hol derived from camphor promotes quantitative ethylation in moderate to good ee,even with low auxiliary loading.150 Up to 95% ee has been achieved using chiral �eeferrocenyl alcohols derived from L-alaninol or L-leucinol.151

In other accounts, the reactivity and enantioselectivity of dialkylzinc additions usingfenchone-based catalysts have been enhanced via sterically induced distortions of thecatalysts,152 camphor disulfonamides have been used as ligands,153 and diisopropylzinchas been added enantioselectively,154,155 the last case involving a non-linear effect in �eean addition to a pyridine aldehyde.

Improvements in addition of diphenylzinc to aromatic aldehydes include a selectivefluorination of a chiral 1, 1′-binaphthyl ligand to boost its catalysis,156 and the addi- �eetion of diethylzinc to boost the yield based on diphenylzinc,157 apparently throughthe formation and reaction of the mixed organometallic, PhZnEt. The latter strat-egy counteracts the 50% loss of phenyl groups inherent in the standard reaction ofdiphenylzinc.

Synthetic and kinetic aspects of ethylation of cyclohex-2-enone and of aceto-phenones using the mixed organometallics, Et3ZnM (M = Li, Na, K), have beenreported.158

For more additions of zinc and other organometallics, see under Imines above.

Addition of Other Organometallics

Protected α-branched amines have been prepared diastereoselectively by copper(I)-mediated addition of Grignards to chiral p-toluenesulfinimines.159 The mechanisms �de

of stereoselective additions of chiral Grignard reagents, particularly those with suchα-amino substituents, has been reviewed.160

�eeMolecular recognition of particular conformations of α,β-unsaturated carbonyl com-

pounds by aluminium tris(2,6-diphenylphenoxide) allows new regio- and stereo-sele-ctivities in alkylation of these substrates.161

Triethylaluminium has been added enantioselectively to aldehydes.162 �eeDiastereoselective addition of organometallics to (−)-menthone is activated by �de

anhydrous cerium(III) chloride.163


Ab initio methods have been used to compare the reaction of organotin enolateswith and without a bromide ion coordinating the tin.164

Starting from a variety of aryl and alkyl ketones with a pendant ortho-bromophenylfunction, intramolecular catalytic aryl palladation of the ketone (to give the cyclicalcohol) has been achieved in moderate to good yields, using a phosphinopalladium(II)system.165

A range of chiral 1,2-alkoxy alcohols, amines, and ethers have been used as aux-iliaries for addition of BuLi and BuMgCl to benzaldehyde and for reduction of �eeacetophenone by lithium aluminium hydride.166 The enthalpic and entropic compo-nents of the diastereoselectivity of addition of BunLi to α-alkoxyaldehydes have been �de

separated; these contributions are also substantially solvent dependent.167

A number of observations concerning stereocontrol in the addition of lithium eno-lates of 1,3-dioxolan-4-ones to aldehydes have been disputed, based on reassign-ments both of structures and of dominant conformations of several key adducts.168 A �de

reassessment of the utility of chiral dioxolanones in diastereoselective condensationsis included.

Kinetic and thermodynamic influences on the course of the addition of organo-lithiums to formaldehyde and acetaldehyde have been calculated for both monomericmethyllithium and lithium dimethylamide, and for their homo- and hetero-dimers.169

Ester enolizations mediated by lithium diisopropylamide (LDA) have been stud-ied in four commonly applied solvent systems: THF, ButOMe, HMPA–THF, andDMPU–THF170 [DMPU = 1, 3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidone]. Therates of these reactions are nearly the same (varying only by a factor of 5), but this dis-guises four mechanisms in which solvation, and in particular LDA aggregation, varyconsiderably. The reasonable rate of reaction achieved with even the hindered andpoorly coordinating methyl t-butyl ether belies the common assumption that stronglycoordinating ligands are required for high reactivity in alkali metallations. The authorsfurther caution that their results underline that ‘relative rate constants’ are of little usein probing organolithium mechanisms. In a further study in which formation of mixedaggregates was maximized, the nature of such aggregates has been probed by 6Li and15N NMR. To a first approximation, formation of such aggregates is a form of autoin-hibition, as they do not provide efficient routes to product.171 A 2 : 1 stoichiometriclithium amide–lithium enolate mixed aggregate ‘trimer’ has been prepared.172 Derivedfrom the lithium enolate of pentan-3-one and the lithium amide of an (S)-valinolderivative, the structure has been studied by X-ray crystallography and 6Li NMR.

The Wittig Reaction, and Variants

Counterion effects have been studied in the Wittig reactions of triphenylphosphoniumand triphenylarsonium salts with aldehydes.173 Only those salts which exhibited fastintramolecular proton exchange between counterion and activated methylene groupcan react with aldehyde, a criterion easily observable in the absence of proton-carboncoupling in the proton-coupled 13C NMR spectrum (i.e. JC,H = 0 Hz). An effectivelimit can thus be placed on the pKa of the counterion’s conjugate acid, below whichreaction will not occur.


(E)- and (Z)-enenitriles (40), previously prepared by reaction of cyanoacetic acidwith isatin (39) and subsequent base-catalysed decarboxylation, have now been syn-thesized in one step by reaction with cyanomethylene(triphenyl)phosphorane.174

(39) (40)

N

H

ON

H

O

CHCNO

Ph3P CHCN

Replacement of phenyl(s) with pyridyl(s) leads to greater Z-stereoselectivity inthe Wittig reaction.175 Although the yield is severely lowered with BunLi as base, �de

removal of lithium cation [by using e.g. sodium bis(trimethylsilyl)amide as base]restores similar yields to those found with a triphenylphosphorane. Even one 2-pyridylsubstituent raises the Z-preference dramatically.

High cis selectivity for conjugated dienes has been achieved in the Wittig reac-tion of 2-alkenyltriphenylphosphonium salts by ‘arming’ the phenyl moieties with �de

o-methoxymethoxy substituents.176

The ionic solvent 1-butyl-3-methylimidazolium tetrafluoroborate facilitates theWittig reaction, including workup and solvent recycling, and shows reasonable E-selectivity.177

The Wittig reaction of vanillin (3-methoxy-4-hydroxybenzaldehyde) andPh3P=CHCO2R (R = Me, Et) gave 8-methoxycoumarin (41) in addition to theexpected alkene product; a mechanism is proposed.178

(41) (42)

O

OMe

OPh

Ph

O

O

X Ph

The utility of a range of recently developed computational methods for predictingthe outcome of organic reactions in solution has been demonstrated for the Wittigreaction, and other examples.179

2-Benzylidene propane-1,3-trione (42; X = CH) undergoes a range of reactions ofsynthetic and mechanistic interest with phosphorus ylids, as does the imine (X = N).180

Di-, tri-, and tetra-substituted alkenes can be prepared when P -diphenyl(alkyl)(N -carboxymethyl)phosphazenes, R1R2CHP(Ph)2=NCO2Me, are metallated with BunLi


and reacted with aldehydes or ketones.181 The Wittig-type reaction is proposed toproceed via a (β-hydroxy)phosphazene (which is isolable), followed by an oxaphos-phetane intermediate.

6-Methyl-2-thiouracil reacts with Wittig–Horner reagents; for example, methyl(diethoxyphosphinyl)acetate gives 2-(ethylthio)-6-methyl-4(1H)-pyrimidinone.182

Sulfinylmethyl-substituted diphenylphosphane oxides, Ph2P(=O)CH2S(=O)R (R = �de

Me, Ph, C6H4-p-Me), undergo Horner–Wittig reaction with aldehydes in good yieldand with excellent E-selectivity.183

A model aza-Wittig reaction:

X3P=NH + O=CHCO2H −−−→ X3P=O + HN=CHCO2H

has been studied theoretically for three X substituents, Me, H, and Cl.184 The reactionis found to be significantly more favourable for the first two.

A series of 1, 3, 2λ5-oxazaphosphetidines bearing the Martin ligand [this o-cumylalcoholate ligand is typically introduced using LiC6H4C(CF3)2OLi]185a have beenprepared, e.g. (43; Tip = 2, 4, 6-Pri3C6H2), and their structures determined by X-raycrystallography and NMR.185b That such compounds are intermediates in aza-Wittigreactions is supported by the results of their thermolysis: moderate heat gives the cor-responding imine (44) and cyclic phosphinate (45). The oxazaphosphetidine structurecan also form an iminophosphorane on thermolysis, but this is reversible. However, atrapping experiment identified its presence. Thus, compounds such as (43) have tworeactivities: as an oxaphosphetane and as an azaphosphetidine.

(44)(43) (45)

PO

O

N POHPh

CF3CF3

Tip

F3C CF3F3C CF3

N

F3C

F3C

Ph

TipO

+ PhMe

140°C

Benzo[b]thieno[3,2-b]pyridines (47) have been prepared by reaction of enones orenols with N -(3-benzo[b]thienyl)iminophosphoranes (46), apparently via aza-Wittigelectrocyclization, i.e. the product of attack of the imino nitrogen at the carbonylgroup.186 In an alternative pathway, the carbonyl can be attacked by the α-thienylcarbon to give an isomeric product (47, with R1, R2 reversed). The latter productis observed in most cases studied, and is favoured for α,β-unsaturated aldehydes.Both the N - and C-reactivities of the iminophosphorane are significantly enhancedby progressive methyl-for-phenyl substitution at phosphorus, presumably by lesseningelectron withdrawal towards the phosphorus.


S S

NR2

R1

(47)(46)

N P R4

R5

R3 R1CH CHCOR2

A stereoselective synthesis of tetrasubstituted alkenes via olefination of ketones hasbeen reported.187 An ynolate salt, RC≡COLi, has been reacted with para-substitutedacetophenones and with para-(mono)substituted benzophenones: plots of (�G �=

E −�G �=

Z) versus σ for these series suggest a stereoelectronic control of the stereochem-istry.

(E)- and (Z)-isoxazoles (49) have been prepared from 2-substituted 1-azabicyclo[2.2.2]octan-3-ones (48) via Peterson olefination with 3-methyl-5-trimethylsilanyl- �de

methyl isoxazole.188 The reaction, which shows some R-dependent E/Z-selectivity,requires an organolithium base. It is suggested that the lithium becomes covalentlyattached α- to silicon, while simultaneously coordinating to the carbonyl oxygen.

(49)(48)

N

O

R N R

O

N

Me

Efforts to switch the ‘normal’ product preference of the Horner–Wadsworth–Em-mons (HWE) modification of the Wittig reaction from E- to Z-α,β-unsaturated esterproducts have been reviewed (53 references).189 A similar review focuses in particular �de

on the use of the reaction for ketone substrates, using various combinations of bases,substituted diethylphosphonoacetates, and tin(II) catalysts to achieve the requisite E-or Z-selectivity.190 The factors involved in the Z-selectivity observed in HWE reac-tions of several methyl diarylphosphonoacetates with aliphatic and aromatic aldehydeshave been probed computationally, and the effects of variation of bases, temperature,and substituents on the aryloxy moieties have been studied.191

Addition of Other Carbon Nucleophiles

A mechanistic study of the catalysis of addition of trimethylsilyl cyanide (TMSCN) toaldehydes by dinuclear chiral (salen)titanium complexes has been undertaken.192 Theresults point to mononuclear intermediates bearing cyanide and benzaldehyde; these


undergo pseudo-dimerization to give a dinuclear complex with a cyanide ligand on onetitanium held in place over a benzaldehyde on the second, with the stereochemistryof the attack controlled by the phenyl of the benzaldehyde minimizing its repulsionwith the salen ligands.

The regioselectivity of addition of TMSCN to β-alkoxyvinyl alkyl ketones, trans-EtOCH=CHCOR (R = alkyl, fluoroalkyl) has been studied for a range of catalysts.193

The alkoxy group is an important factor favouring 1,4-addition, as are higher tempera-tures, bulky R groups, and electrophilic catalysts such as iodine. Nucleophilic catalystssuch as triethylamine, in contrast, catalyse 1,2- and 1,4-addition to approximately thesame extent.

TMSCN has been added in up to 59% ee to aldehydes, to give the TMS ethers of the �eecorresponding cyanohydrins, using the monolithium salt of (S)-BINOL as auxiliary.194

The reaction may involve hypervalent silicon intermediates. Using the monolithiumsalt of the (R, R)-(−)-salen-derived auxiliary (50), the ees are raised to 97%.195

The finding that unprotected α-aminoaldehydes can be generated in solution andsustained therein without significant epimerization suggests that they are viable inter-mediates in asymmetric synthesis.196 Nucleophilic solvent attack at the carbonyl isgenerally faster than racemization, but the reversibility of such adduct formation means �eethat the adducts can remain viable as ‘masked’ equivalents. Cyanide attack yields α-aminocyanohydrins, which dimerize on standing in methanol, yielding diastereomeric2,5-dicyanopiperazines (e.g. 51, from phenylalaninal) via sequential inter- and intra-molecular Strecker reactions.

(51)(50)

NN

ButBut

ButBut

OH HO

HN

NH

CH2Ph

NC

CH2Ph

CN

Protection of the carbonyl groups of aldehydes and ketones as their O-methoxycar-bonyl cyanohydrins, >C=O → >C(CN)OCO2Me, has been developed and its scopeas a strategy investigated.197 The cyanohydrin can be formed in high yield usingmethyl cyanoformate and an excess of secondary alkylamine at room temperaturein solvents such as THF or ethyl acetate, in an atmosphere of air, as long as grossmoisture is avoided. At least two steps are involved in formation of the adduct, assolvents which give a fast initial reaction ultimately prove to be fairly slow, whereas forTHF the reverse is observed. The reaction works best for unconjugated aldehydes andketones, to the extent that they can be selected over those containing enone or benzoylfunctions. The protecting group shows a useful stability profile, resisting aqueous


Brønsted acids, common Lewis acids, many oxidants, and also reducing agents suchas DIBAL and sodium borohydride. Quantitative deprotection of protected ketones isachieved in minutes in THF using methoxide–methanol, although this does not workfor the protected aldehydes.

Tetraethylammonium silver(I) cyanide, Et4NAg(CN)2, reacts with α-alkoxyal-dehydes in the presence of MgBr2 · OEt2 to give cyanohydrins with high syn-diastereo-selectivity.198

Scandium(III) triflate catalyses the addition of 2,2-dimethoxypropane (i.e. the dime-thyl acetal of acetone) to o-hydroxybenzaldehydes to yield 2,4-dimethoxy-2-methyl-benzopyrans (52).199

Aldehydes are trifluoromethylated to the corresponding trifluoromethylcarbinolusing fluoroform deprotonated in DMF.200a,b Dimsyl-K [K+−CH2S(Me)=O] is usedto deprotonate the fluoroform. Normally, the CF3

− ion thus formed would decomposeexothermically, even at low temperature. However, in the presence of DMF it istrapped as the alcoholate salt (53), a masked form of CF3

−, which then attacksthe aldehyde carbonyl, regenerating DMF. The zinc and copper alcoholates are alsodescribed. Support for the postulated mechanism is also cited.200c

(52) (53)

O

OMe

OMe

Me OK

F3CNMe2

H

A review of nucleophilic trifluoromethylations by (trifluoromethyl)trimethylsilane(Me3SiCF3) has covered reactions with aldehydes, ketones, enones, carbohydrates,esters, amides, imines, and nitrones.201

A review of the addition of acyl carbanion equivalents to aldehydes, enones, andenolates focuses on asymmetric heterazolium catalysis (63 references).202 ‘Tuning’ �eeof reaction conditions allows the addition of vinyl sulfonium ylids to aldehydes togive either the cis- or trans-vinyloxirane; the mechanisms underlying this switchable �de

stereoselectivity are discussed.203 Homoallylic thiols have been condensed diastereos-electively with aldehydes, using an indium(III)-mediated cationic cyclization, to givemulti-substituted thiacyclohexanes.204 Sulfur-stabilized carbanions have been addeddiastereoselectively to chiral cyclohexanones.205

Miscellaneous Additions

Exploiting a ‘bis(siloxy) effect’, 1,2-trans-disubstituted benzocyclobutane (54; TBS =t-butyldimethylsilyl) undergoes a thermal hetero-Diels–Alder cycloaddition with alde-hydes as dienophiles to give single isomer products (56).206 Evidence for o-quinone �de

dimethide intermediates (55) is presented. The reaction gives analogous products


(55)(54) (56)

O

OTBS

OTBS

R

OTBS

OTBS

OTBS

OTBS

RCHO

when either toluene-4-sulfonyl cyanide or N -benzylidene phenylsulfonamide are usedinstead of aldehyde.

Catalytic asymmetric hetero-Diels–Alder reactions of carbonyl compounds and ofimines have been reviewed (110 references).207

�de

α,β-Unsaturated thioaldehydes and thioketones, prepared in situ from the corre-sponding carbonyl compounds and bis(dimethylaluminium) sulfide, can act as hetero-diene and as dienophile.208 They are found to undergo Diels–Alder self-dimerizations,both ‘head-to-head’ and ‘head-to-tail’; the kinetic and thermodynamic controls invol-ved have been calculated.

In other reports, arylaldehydes have been alkylated using alkylboron chloride rea-gents,209 a review of addition reactions of aldehydes with tetramesityldi- and germa-silene argues the case for biradical intermediates,210 the relative reactivity of thevinyl and carbonyl double bonds of trans-benzylidene-3-nitroacetophenone towardsnucleophiles has been predicted,211 and the addition of the carbenoid CH2ClLi toformaldehyde in THF has been examined by ab initio methods.212

Enolization and Related Reactions

A combination of ab initio and molecular mechanical calculations has been usedto shed light on the two steps catalysed by enolase enzyme, viz. deprotonation of 2-phospho-D-glycerate to give an enolic intermediate, followed by loss of the β-hydroxylgroup.213 Owing to the changeover in charge type between the steps, two divalentmetal cations that favour the first disfavour the second. The active site has resolvedthis tension by means of stabilizations from polar and charged groups arranged in twodirections in space, almost perpendicular, which prevent a stabilization in one stepacting as a destabilization of the other.

The ion cyclotron resonance method has been used to measure the acidities of ninesimple stable enols and eight ketones in the gas phase, yielding tautomeric constantsfor seven keto–enol systems.214 All of the enols [Mes2C=C(OH)R] were stabilizedby the bulky mesityl group (2,4,6-trimethylphenyl). Correlations between ketones andenols, between gas phase and various solvents, and with Hammett σ values for arange of R groups containing para-substituted-phenyl are discussed, in addition to acomparison with calculated values.

The acidity of cyclopentanones and their 1,2- and 1,3-hetero analogues, and theirbenzannelated derivatives, has been calculated in the gas phase and in DMSOsolution.215 The results for the relative stabilities of keto, enol, and enolate structures


have been compared with those for acyclic analogues (in both phases) to facilitateseparation of the deprotonation energy of the CH acids into inductive, resonance, andsolvation effects.

The rates of exo- and endo-deprotonation of camphor, norcamphor, and dehydronor-camphor have been calculated in a quantum mechanical study of stereoelectronic,torsional, and steric effects on the base-catalysed enolization of these ketones.216

The thermodynamics of the keto–enol–enolate system have been measured for 3-nitrobutanone (57) in water, via kinetic measurements of enolization and ketonizationreactions, and determination of the ionization constant.217 The values of pKT and pKa

(ketone) are 2.34 and 5.15 respectively.

(58)(57) (59)

O

NO2

NO2

H

HX

HN O

X

H

Tautomeric isomerism and conformism have been evaluated computationally formodel compounds exemplifying three classes of nitroethylenes (58): (i) 2-nitrovinylalcohol (X = O); (ii) 2-nitrovinylamine (X = NH); and (iii) 1-nitropropene (X =CH2).218 While in all three cases structure (58) represents the global minimum,the extent of keto–enol, imine–enamine, and nitro–aci-nitro tautomerism is subtlydependent on the interaction of such closely spaced functional groups, and largehydrogen-bonding effects are also observed.

Ab initio calculations suggest that nitro substitution stabilizes the enol tautomer ofacetaldehyde by 8.7 kcal mol−1 (relative to the aldehyde), and stabilizes the enaminetautomer of acetaldimine by 2.5 kcal mol−1; the aci-nitro forms were also investi-gated.219

The position of keto–enol equilibrium in 2(1H)-pyridones substituted with nitro,amino, or carboxylic acid groups in the 3-position (59) have been predicted for thegas phase and for DMSO solution.220 Intramolecular hydrogen bonding is suggestedto favour the enol in the nitro case.

Malonaldehyde is a continuing source of interest: three sets of calculations considerketo–enol tautomerism with an explicit treatment of several likely conformers,221 theenolization process and how it compares in the dithio and diseleno analogues (andin thio- and seleno-acetaldehyde),222 and the potential energy function for hydrogentransfer in the case of the cation of malonaldehyde.223

Other calculations have looked at tautomerism in tropolone,224 halogenated keto-nes,225 β-diketones containing chlorine and sulfur substituents,226 and 3-hydroxy-2-pyridinethione.227

For details of the keto–enol tautomerism of 9-formylfluorene, see Oximes above.


Enolates

Base treatment of pentynones, RCO(CH2)2C≡CCO2Me, produces the correspond-ing enolates, which can cyclize to furan derivatives.228 The homologous hexynonesyield pyrans.

The mechanism of the reaction of β-keto sulfoxides with sulfur electrophiles hasbeen probed in a stereochemical and configurational study of the intermediate eno-lates.229

Unexpected results in the electrochemical reductive cleavage of α-substituted ace-tophenones have been interpreted in terms of the thermodynamic and kinetic basicitiesof the carbon and oxygen ends of the enolates.230

The reaction of epoxides with metal enolates of ester, ketone, and amide substrateshas been reviewed (61 references), with a particular emphasis on lithium salts.231 Achi-ral lithium enolates have been protonated with high enantioselectivity in an aqueousmedium, using a chiral tetraamine.232 A chiral lithium amide has been used to convert4-t-butylcyclohexanone to its (S)-enolate in 95% ee; the enolate is a handy entry �eepoint for useful chiral compounds.233 Chiral anilines can protonate amide enolatesenantioselectively.234

Oxidation and Reduction of Carbonyl Compounds

Oxidation Reactions

A Hammett relationship has been found for the rates of oxidation of aromatic acetalsby pyridinium fluorochromate in aqueous acetic acid; although electron-withdrawinggroups favour oxidation, ρ is low.235

Studies of sugars include manganese(III) oxidation of aldo- and keto-hexoses inacid,236 electron transfer reactions of iron(III) perchlorate with D-xylose, -ribose,and -arabinose in the presence of 2,2′-bipyridyl,237 the oxidation of D-xylose and-ribose and of L-arabinose by 1-chlorobenzotriazole in aqueous hydroxide,238 andother investigations of reducing sugars: the kinetics of iridium(III) catalysis of oxi-dation by N -bromosuccinimide in perchloric acid,239 the mechanism of oxidationby N -bromoacetamide in perchloric acid with Pd(II) catalysis,240 and kinetics ofruthenium(III)-catalysed oxidation by chloramine-T in alkaline medium.241

The oxidation of cyclohexanone imines by m-chloroperbenzoic acid to produceoxaziridines shows evidence of regio- and stereo-selectivity.242 Whereas a 2-methoxysubstituent gives the expected oxidant attack anti to the substituent, the effect of a 2-hydroxy group is to ‘steer’ the oxidant towards syn attack. The method holds promisefor asymmetric synthesis of oxaziridines.

The kinetics of the oxidation of benzalaniline by isoquinolinium chlorochromate insulfuric acid have been studied.243

The oxidation of linear and branched aldehydes by dioxygen and by m-chloroper-benzoic acid has been studied experimentally and computationally.244 Linear aldehydesgive the corresponding carboxylic acids, whereas α-branched aldehydes give for-mates. Rearrangements of the peracid–aldehyde adducts are discussed: conformational


effects in these adducts can explain some of the differences between the linear andbranched cases.

Rates of oxidation of 36 monosubstituted benzaldehydes by hexamethylenetetra-mine–bromine in aqueous acetic acid are reported, including investigations of sub-stituent, steric, isotope, and solvent effects.245 Other kinetic studies of benzaldehydesinclude oxidation of p-methoxy and o-hydroxy substrates by chloramine-B (N -sodio-N -chlorobenzenesulfonamide) in HCl,246 and oxidation by imidazolium dichromatein aqueous acetic acid.247

Kinetics of the oxidation of crotonaldehyde by molecular oxygen in ethyl acetate248

and its epoxidation by quinolinium fluorochromate,249 the oxidation of aliphatic alde-hydes by t-butyl hypochlorite in aqueous acetic acid,250 and a shock-tube study of theoxidation of acetaldehyde at high temperature (1320–1897 K)251 have been reported.

The mechanism of oxidation of ketones by permanganate has been re-examined ina kinetic study of RCH2COMe (R = H, Me, OH, and COMe).252 In acidic solution,nucleophilic addition to the carbonyl carbon is evidenced, with decomposition ofthe resultant permanganate ester as the rate-determining step. At higher pH, electronabstraction from the enolate becomes important, but a concerted mechanism mayalso operate. Some insightful comparisons with and contrasts between oxidation andhalogenation are noted for both acidic and alkaline conditions.

In other reports, flavonoids have been proposed as scavengers of peroxynitrite(ONO2

−), but a kinetic investigation suggests otherwise, and also discounts sucha role for dihydroxybenzenes or esters.253 The role of aldehyde mediation in the oxi-dation of alkenes to epoxides by molecular oxygen has been examined.254 A kineticstudy has looked at the reactivity of carbonyl oxides (R2COO) towards benzalde-hyde in acetonitrile solution: the reaction gives either ring oxidation products or the1,2,4-trioxolane.255 Benzaldehydes are oxidatively esterified to methyl benzoates byhydrogen peroxide in methanol, with vanadium pentoxide catalysis.256 Working innear-quantitative yield at 0 ◦C in a few hours, the transformation appears to involve avanadium peroxide attack on the hemiacetal.

Unusual disproportionation rearrangements of 1,6-diketones in acid have beenreported, where one carbonyl is in a ring and the other is in an α-side-chain.257

For cyclopentanones (60) with a keto function on C(4) of the side-chain, refluxing in1 mol dm−3 H2SO4 for 1–2 days yields a cyclopentenyl carboxylic acid (61). Labellingstudies (arrowed) indicate that the side-chain carbonyl carbon of (60) ends up in thecyclopentenyl double bond of (61), beside the new branch point. Thus one carbonyl of(60) participates in a ring opening and the other in a cyclization. When the ring is six-membered, as in (62), only cyclization occurs, giving enone (63). Although the authorshave not pinned down the mechanism of this transformation, several mechanistic testexperiments are reported which rule out a number of possibilities.

For other oxidations of aldehydes and ketones, see Atmospheric Chemistry below.

Regio-, Enantio-, and Diastereo-selective Reductions

An enone-selective reduction, with di-n-butyliodotin hydride (Bun2SnIH) as reducing

agent, has been exploited for synthesis of carbocycles.258 A substrate containing both �de


R

O

O R

CO2H

(60) (61)

(62) (63)

O O

O

enone and formyl functions is reduced at the enone, and then undergoes an intramolec-ular aldol reaction. The reduction does not appear to involve radical intermediates.

Tunable ‘green’ reductions of α,β-unsaturated ketones, giving 1,2-, 1,4-, or com-plete reduction products, have been carried out with sodium borohydride together withwater or aqueous micellar solution, with additional chemocontrol provided by cobaltchloride.259

A green selective reduction of aldehydes has been developed using sodium formateand simple equipment.260 In sub-critical water (typically 250–300 ◦C/ca 80 atm), alde-hydes are reduced whereas acyclic or cyclic ketones are not. Reaction times are a fewhours, and the product alcohol can be distilled from the organic fraction. Above 300 ◦C,cyclic ketones are reduced but the acyclics are little affected even at 340 ◦C.

Selective reduction of α,β-unsaturated carbonyl compounds, both at the carbonylgroup and at the vinyl function, has been reviewed (75 references).261

A dozen papers dealt with diastereoselective carbonyl reduction. The exterior fron-tier orbital extension (EFOE) model has been applied to explain the π -facial diastere- �de

oselection in the reduction of 1,3-diheteran-5-ones (64; X = O, S) by lithium alu-minium hydride (LAH).262,263

4-eq-6-ax-Diaryl-5-azaadamantan-2-ones (65) undergo reduction by the action ofsodium borohydride in methanol at 25 ◦C to yield predominantly the (Z)-alcoholproduct, via en attack.264 The results are discussed in terms of steric and electroniceffects, the latter including variation of substituents on the aryl rings.

2-Acyl-1-napthamides (66) with reasonably bulky R groups on the nitrogen (i.e.R2 = Et, Pri , etc.) are intrinsically chiral, open to attack at the ketone from the frontface (as shown), while the amide shields the back. Organolithiums, Grignards, andborohydrides reduce them with high or complete atroposelectivity.265 The use of such �de

neighbouring ‘shields’ to bias attack has been extended to reductions of other functions(acetal to ether, imine to amine), and to whether chelation mechanisms operate.266

The atroposelective reduction has also been investigated for the related 8-formyl-1-naphthamides.267


(65)(64) (66)

X

X

OR

NAr

O

Ar

2

4

5

3

6

1

R1

OO N

R2R2

1

2

8

α-Alkyl-β-hydroxy ketones can be stereoselectively reduced to the corresponding2-alkyl-1,3-diols with a 1,2-syn relationship via the titanium alcoholate, using hydride �de

reagents.268

β-Alkoxy ketones have been reduced by samarium(II) iodide in 99% yield and 98%de, in THF–methanol. However, even modest changes in alkoxy substituent, e.g. from �de

MeO to BnO, result in no reaction.269 Apparently the latter cannot effectively com-plex samarium. Evidence for the selection step involving protonation of a samariumcarbanion is described.

α-Nitro ketones have been reduced by BH3 · SMe2 to the β-nitro alcohols; medi-ation by the strongly coordinating titanium tetrachloride gives fair to excellent anti-diastereoselectivity.270

�de

Chiral hydrazones, R2R3C=N−N(R1)−∗CHEt−CO2Me, were reduced by LAH togive the corresponding hydrazines in 43–100% de; the completely selective cases all �de

bore a trifluoroethyl (F3C−CH2) group as R1 on the nitrogen beside the chiral centre.271

Among many enantioselective reductions, an attempt to improve on the poor enan-tioselectivity seen in (intermolecular) Meerwein–Ponndorf–Verley (MPV) reductionsused a tethered thiol to produce an intramolecular mechanism. In a novel tandemMichael addition–MPV reduction,272 acyclic α,β-unsaturated ketones were convertedto secondary alcohols in up to 98% ee. The method exploits an asymmetric 1,7-hydride �eeshift and a dynamic kinetic resolution via a reversible Michael addition.

Boron reagents and catalysts have been widely deployed. Chiral ketones basedon camphor have been reduced in high ee by a range of borane reagents based onα-pinene, and the results have been compared with theoretical calculations.273 AnN, N -dimethylphosphoramidite based on BINOL catalyses the borane reduction ofacetophenone with 96% ee.274 Chiral (o-hydroxyaryl)oxazaphospholidine oxides have �eebeen used as bifunctional catalysts in enantioselective reduction of ketones.275 An insitu 11B NMR study has been used to probe the mechanism of an asymmetric boranereduction catalysed by a bis-oxazaborolidine.276 Other asymmetric oxazaborolidinecatalysts have been described.277,278

Acetophenone has been reduced enantioselectively using LAH and a chiral inda-nol,279 benzaldehydes have been reduced in 95–99% ee using ruthenium-catalysed �eetransfer hydrogenation,280 and asymmetric reduction of fluorine-containing carbonylcompounds has been reviewed (137 references).281

Conjugated aldehydes have been reacted in the presence of chiral sulfonium salts(67) to give trans-aryl vinyl epoxides in 95–100% ee.282 Alternatively, the aldehydes �eecan act as Michael acceptors and give cyclopropanes. While the product ratio varies


(68)(67)

O S+

R

−OTf

PN

N

NN

MeMe

Me

with aldehyde structure and with solvent, a ‘para-methoxy effect’ is observed withthe catalyst: if R = OMe, the epoxide is the exclusive product.

Although epoxides are often made by reacting an alkene with a peroxide, thismethod is inappropriate if sensitive functional groups are present. An alternative mildapproach which is tolerant of some easily oxidized groups has been developed. Thus, 2mol of an arylaldehyde containing electron-withdrawing groups can be coupled usingP(NMe2)3 to form the corresponding 1,2-diaryl epoxides. Although the trans-isomeris generally favoured, the preference is slight. Several such couplings have now beenpromoted with near-quantitative yield of trans products in the range 92–99%, usingthe tricyclic analogue P(MeNCH2CH2)3N (68), which is apparently more nucleophilicthan P(NMe2)3.283

Other Reduction Reactions

The mechanism of the rhodium(I)-catalysed transfer reduction of carbonyl compoundshas been computed for formaldehyde, acetone, and acetophenone, using RhH(NH3)2

(C2H4)2 as a model hydride complex.284 Mechanisms of hydride transfer to acetophe-none using ruthenium catalysts have been investigated by following the stereochemicaland isotopic outcome in the (near-)identity reaction of (S)-α-deuterio-α-phenylethanoland acetophenone.285

A series of β-stannyl ketones, R1XSn−CHPh−CHR2−COPh, react with sodiumt-butoxide in DMSO or acetonitrile to give elimination or reduction products; themechanisms and relative reactivities have been examined.286

In a one-pot reaction, reductive amination of adamantyl methyl ketone has beenachieved using samarium–iodine to reduce the imine prepared in situ.287

gem-Dichloroarylmethanes, ArCHCl2, have been prepared by refluxing the corre-sponding aldehydes in hexane with boron trichloride; an intermediate alkoxyborondichloride (69) has been isolated and characterized.288

Dialkylboron chloride derivatives have been shown to alkylate aromatic aldehy-des,289a but the reaction fails for the corresponding bromide. When alkylboron dibro-mides are used instead (e.g. 70, in the form of a disulfide complex), alkylation fails.However, reductive bromination to produce the benzyl bromide occurs instead,289b andin high yields. This potentially useful reaction, previously only achieved with trimethy-laminoborohydride–bromine289c or lithium bromide–chlorotrimethylsilane–tetra-methyldisiloxane,289d can be carried out in hexane at ambient temperature.


(69) (70)

OBCl2

ClX

BBr2 SMe2•

Atmospheric Chemistry

Several reports deal with the kinetics and products of reactions of radicals and relatedspecies with carbonyl compounds in the gas phase, in particular those of relevance tocombustion and processes occurring in the troposphere and the upper atmosphere.

To shed more light on the role of volatile organic compounds (VOCs) in the upperatmosphere, rate coefficients for the reaction of chlorine atoms with acetones (RCOMe;R = Me, Et, Pri , CH2CHMe2, CH2Cl, CHCl2) have been measured at 298 K in therange 15–60 mmHg.290

Rate constants for the reaction of biogenic aldehydes such as propanal, butanal,pentanal, and hexanal with OH and NO3 radicals have been measured in the gasphase at 296 K and 1 atm.291 Rate constants for hydroxyl are 2000–3000 timesgreater, suggesting that this reaction is the dominant atmospheric process, with thealdehydes having calculated lifetimes of a few hours during daytime. Other studies ofaldehydes looked at (i) NO3 radicals with butanal and 2-methylpropanal at 263–364K,292 (ii) OH and Cl radicals with four aldehydes, RCHO (R = Et, Pri , Bun, But ) andCl with acrolein and crotonaldehyde, at 243–372 K,293 and (iii) bromine radicals withC1 –C4 (straight-chain) aldehydes at 240–300 K.294

A more extensive study of the gas-phase reactions of chlorine and bromine atomswith formaldehyde and acetaldehyde, and several of their isotopomers, measured thekinetics at ambient temperature and pressure, using FT-IR spectroscopy.295 Rate con-stants and deuterium isotope effects are reported for the formation of HX + CO (theonly products for formaldehyde), and HX and a MeCO radical (the dominant pathwayfor acetaldehyde). These parameters were also calculated from theory, and discrep-ancies between calculated and experimental results suggest a role for a weak adductformed between the halogen and the aldehydic oxygen.

Phenyl radical has been calculated to have three main reaction channels withformaldehyde: hydrogen abstraction and addition to the carbon have modest barriers(0.8 and 1.4 kcal mol−1, respectively), while reaction at oxygen to produce PhOCH2

requires 9.1 kcal mol−1.296 PhCH2O, the product of addition to carbon, can frag-ment to benzaldehyde and hydrogen with a barrier of 19.4 kcal mol−1. The hydrogenabstraction reaction to produce benzene and a CHO radical has also been separatelyinvestigated, by experiment and computation.297

The HO2 radical does not react with simple ketones in the gas phase at 298 K,except possibly in the reversible formation of weakly bound adducts.298

The gas-phase reactions of two silyl cations, Me3SiOSi+Me2 and Me3CH2SiOSi+Me2,with acetone have been studied.299


For reaction of formaldehyde acetals, see Acetals above. For reaction of hydroxylradical with ketene, see Ketenes above.

Other Reactions

Derivatives of flavone and isoflavone (71, 72, R = H) occur widely in the diet, andhave been implicated in the prevention of cancer and other diseases. Frontier molecularorbital and thermodynamic calculations have been employed to probe the relationshipbetween structure and reactivity, looking at reactions of acids and bases (at the centralcarbonyl oxygen and carbon, respectively), and of electrophiles [at C(3) of (71) andat C(3) and C(1′) of 72)], and nucleophiles [at C(2) and C(1′) of (71) and at C(2)of 72)].300 Electron supply/demand variation has been achieved through variationof R at the 4′-position. Calculations for the gas-phase reactions correlate well withexperimental reactivities in the literature, and also with behaviour in aqueous solution,despite distinct changes in stability between the phases.

(72)(71)

O

O

O

O

R

R

1′2

4′

3 1′

2

4′

3

The Schonberg reaction, in which a diarylthione reacts with a diaryldiazomethaneto give a 4,4,5,5-tetraaryl-1,3-dithiolane (73), has been further investigated over arange of temperatures and substrates.301 The unusual 2 : 1 stoichiometry of the reaction(not found for diazomethane itself) is explained in terms of a sequence of two 1,3-dipolar cycloadditions, linked by a 1,3-dipolar cycloreversion. Also observed wasthe S-methylide of thiobenzophenone (74), the reaction of which was studied with arange of thiocarbonyl compounds.302 1,3-Dithiolanes are again produced, even withvery bulky aryl substituents.

(74)(73)

S

SAr2

Ar2

C−S

CH2

Ph

Ph

+

Benzoin, PhCH(OH)COPh, undergoes three different reactions with dibromotriph-enylphosphorane, depending on the conditions, to give either benzyl (the α-dicarbonyl),desyl bromide (the substitution product), or benzyl phenyl ketone (deoxybenzoin).303


1-Aryl-2-(arylamino)ethanones, under Vilsmeier conditions, give the N -formylproduct (apparently via a cyclic oxazolidine intermediate), rather than the expectedN -formylvinyl chloride expected.304

Aldehydes, RCHO, can be converted to benzyl ketones, RCOCH2Ar, using aryl- �eediazomethanes generated in situ from tosylhydrazones.305,306

The scope for α-arylation of ketones has been extended considerably, using pal-ladium(II) catalysis.307 In some cases, unliganded Pd(OAc)2 is sufficient; in others,electron-rich phosphines accelerate the reaction. In many cases, the use of strongbases is no longer required, with potassium phosphate sufficing. The method has beenextended to the arylation of diethyl malonate, cyclic β-diketones, and nitroalkenes.

By appropriate choice of solvent, AccufluorTM NFTh [(75), 1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate)] fluorinates either the α-position orthe aryl ring of a range of aryl alkyl ketones.308 The use of elemental fluorine forselective direct fluorination of enolizable carbonyl compounds has been the subject ofa short review.309

A new self-cyclization of a linearly conjugated pentadienal (76) apparently proceedsvia Z- to E-isomerization followed by formation of a cyclocarbocation intermediate,stabilized by the allylic silicon substituent.310 The product spiro[4.5]decane system(77) occurs in natural sesquiterpenes.

N+

N+

OH

F

(BF4−)2

(Z)-(76)(75) (77)

R R

CO2EtMe3Si

FeCl3

O

Paterno–Buchi cycloaddition of formaldehyde or benzaldehyde to 2-furylmethanolsyields 2,3- and 4,5-adducts.311 The regio- and stereo-selectivity has been studied fora range of substrates, and evidence for an electron-transfer mechanism is presented. �ee

2,3-Difunctionalized cyclopropanecarbaldehydes have been prepared stereoselec-tively, via addition of N2CHCO2Me to a furan, with subsequent opening of thefive-membered ring with ozone.312 Diastereoselective additions of nucleophiles to �de

the products are described.The reactivities of several trihalomethyl ketones, R1R2CHCOCX3, have been inves-

tigated under basic conditions, examining the competition between 1,2- versus 1,3-elimination and nucleophilic substitution. Formation of ketene was not detected. Thepredominant formation of Favorskii products (i.e. 1,3-) is contrasted with the 1,2-elimination found for the corresponding trihalomethylacetamides, to give isocya-nates.313 Steric effects have been studied in the reaction of 1-adamantyl bromomethylketone with metal alcoholates under Favorskii conditions.314


In an exploration of the synthetic utility of haloacetylated enol ethers, the reactionsof several β-alkoxyvinyl trihalomethyl ketones (78; X = F, Cl; R1/R2/R3 = H/alkyl)with N -methylthiourea have been examined in acidic methanol.315

(78)

CX3

O

OR3

R1

R2

Cyclic ketones can be carbonylated with ring cleavage to give diesters usingPdCl2 –CO–MeOH: for example, cyclohexanone gives mainly dimethyl pimelate[MeO2C(CH2)5CO2Me].316 13CO labelling experiments suggest that Pd(II)–CO2Meinsertion across the double bond of the enol tautomer is followed by Pd(II) eliminationand acid-catalysed ring cleavage to give the second ester group.

Decarbonylative functionalization of aldehydes, RCHO (R = primary or secondaryalkyl), into alkyl halides, xanthates, nitriles, and several other functionalities has beenachieved by (i) preparing a peroxyacetal from the aldehyde and 1,1-dimethylprop-2-enyl hydroperoxide, and then (ii) inducing its homolytic cleavage.317 Rates of thet-butyl hydroperoxide-induced decarbonylation of anisaldehyde and caprylic aldehydehave been measured.318

Racemic norbornene aldehydes have been resolved via a kinetically controlledhaloetherification of ene acetals.319 �de

A regiochemical study of the ring expansion of 2-substituted ketones (cyclopent- andcyclohex-anones) via insertion of hydroxyazides shows little selectivity for small sub-stituents (Me, Et), but larger groups result in migration of the more highly substitutedcarbon.320 The opposite happens with inductively electron-withdrawing substituents(OMe, Ph, Br).

A kinetic study of the pyridinolysis of phenacyl bromides, in which a range ofsubstituents have been placed on both phenyl and pyridine rings, indicates a mech-anistic switchover as the basicity of the pyridine changes.321 The biphasic Brønstedplot obtained is attributed to the rate-determining step changing from formation of atetrahedral intermediate to its breakdown.

Synthetic routes to the anticholinesterase tacrine and structure–activity relationshipsin tacrine derivatives have been reviewed (69 references),322 as has the asymmetric �eesynthesis of α-substituted serines (88 references).323

References1 Gift, A. D. and Ben-Amotz, D., J. Phys. Chem. A, 104, 11459 (2000).2 Butler, G. M., Brown, S. N., Boger, R. M., Ferfolia, M. T., Fitzgibbons, A. C., Jongeling, A. C., Kelle-

her, S. J., Malec, A. D., Malerich, J., and Weltner, A. N., Org. Lett., 2, 4125 (2000).3 Muntean, L., Grosu, I., Mager, S., Ple, G., and Balog, M., Tetrahedron Lett., 41, 1967 (2000).4 Becker, K. H. and Thuner, L. P., Ber. Bergische Univ. Gesamthochsch. Wuppertal, Fachbereich 9, Phys.

Chem., 1 (1999); Chem. Abs., 133, 43116 (2000).


5 Deslongchamps, P., Dory, Y. L., and Li, S., Tetrahedron, 56, 3533 (2000).6 Garesio, F., Kardos, L., Bonnevie, C., Luche, J.-L., and Petit, S., Green Chem., 2, 33 (2000); Chem.

Abs., 133, 43735 (2000).7 (a) Mattheus de Roode, B., Zuilhof, H., Franssen, M. C. R., van der Padt, A., and de Groot, A., J.

Chem. Soc., Perkin Trans. 2, 2000, 2217; (b) Gunata, Z., Vallier, M. J., Sapis, J. C., Baumes, R., andBayonove, C., Enzyme Microb. Technol., 16, 1055 (1994).

8 Devel, L., Vidal-Cros, A., and Thelland, A., Tetrahedron Lett., 41, 299 (2000).9 Scheffler, G., Behrendt, M. E., and Schmidt, R. R., Eur. J. Org. Chem., 2000, 3527.

10 Hanessian, S. and Lou, B., Chem. Rev., 100, 4443 (2000).11 Mikkola, S., Koissi, N., Ketomaki, K., Rauvala, S., Neuvonen, K., and Lonnberg, H., Eur. J. Org.

Chem., 2000, 2315.12 Morpurgo, S., Brahimi, M., Bossa, M., and Morpurgo, G. O., Phys. Chem. Chem. Phys., 2, 2707 (2000);

Chem. Abs., 133, 208047 (2000).13 Namchuk, M. N., McCarter, J. D., Becalski, A., Andrews, T., and Withers, S. G., J. Am. Chem. Soc.,

122, 1270 (2000).14 Kaczmarek, J., Kaczynski, Z., Trumpakaj, Z., Szafranek, J., Bogalecka, M., and Lonnberg, H., Carbo-

hydr. Res., 325, 16 (1999); Chem. Abs., 132, 347803 (2000).15 Krishnamurthy, R., Guntha, S., and Eschenmoser, A., Angew. Chem., Int. Ed. Engl., 39, 2281 (2000).16 Inoue, H., Nakayama, H., and Tsuhako, M., Carbohydr. Res., 324, 10 (1999); Chem. Abs., 132, 279401

(2000).17 Garcia-Tellado, F., de Armas, P., and Marrero-Tellado, J. J., Angew. Chem., Int. Ed. Engl., 39, 2727

(2000).18 Jung, K.-H., Muller, M., and Schmidt, R. R., Chem. Rev., 100, 4423 (2000).19 Hou, H., Wang, B., and Gu, Y., Phys. Chem. Chem. Phys., 2, 2329 (2000).20 Wang, Y. and Toscano, J. P., J. Am. Chem. Soc., 122, 4512 (2000).21 Ma, N. L. and Wong, M. W., Eur. J. Org. Chem., 2000, 1411.22 Nguyen, M. T., Raspoet, G., and Vanquickenborne, L. G., J. Phys. Org. Chem., 13, 46 (2000).23 Stankovic, S. and Espenson, J. H., J. Org. Chem., 65, 5528 (2000).24 Wu, P. and He, S., Wuli Huaxue Xuebao, 16, 243 (1999); Chem. Abs., 132, 321591 (2000).25 Wang, M., Liu, Q., Zhao, M., and Li, J., Dongbei Shida Xuebao, Ziran Kexueban, 48 (1999); Chem.

Abs., 132, 250689 (2000).26 Arnaud, R., Adamo, C., Cossi, M., Milet, A., Vallee, Y., and Barone, V., J. Am. Chem. Soc., 122, 324

(2000).27 Leclerc, E., Mangeney, P., and Henryon, V., Tetrahedron: Asymmetry, 11, 3471 (2000).28 Yun, J. and Buchwald, S. L., J. Org. Chem., 65, 767 (2000).29 Garcia Ruano, J. L., Alcudia, A., del Prado, M., Barros, D., Carmen Maestro, M., and Fernandez, I.,

J. Org. Chem., 65, 2856 (2000).30 Cimarelli, C. and Palmieri, G., Tetrahedron: Asymmetry, 11, 2555 (2000).31 Shimizu, M., Fujisawa, T., and Abe, K., Res. Rep. Fac. Eng. Mie Univ., 24, 13 (1999); Chem. Abs.,

133, 281373 (2000).32 Lewkowski, J., Rzezniczak, M., and Skowronski, R., Heteroat. Chem., 11, 144 (1999); Chem. Abs.,

132, 321912 (2000).33 Jimeno, C., Subba Reddy, K., Sola, L., Moyano, A., Pericas, M. A., and Riera, A., Org. Lett., 2, 3157

(2000).34 Sato, I., Kodaka, R., Shibata, T., Hirokawa, Y., Shirai, N., Ohtake, K., and Soai, K., Tetrahedron:

Asymmetry, 11, 2271 (2000).35 Morgan, P. E., McCague, R., and Whiting, A., J. Chem. Soc., Perkin Trans. 1, 2000, 515.36 Aubrecht, K. B., Winemiller, M. D., and Collum, D. B., J. Am. Chem. Soc., 122, 11084 (2000).37 Kolotuchin, S. V. and Meyers, A. I., J. Org. Chem., 65, 30189 (2000).38 Yoo, S.-E., Gong, Y.-D., and Kim, S.-K., Bull. Korean Chem. Soc., 20, 441 (1999); Chem. Abs., 132,

49669 (2000).39 Roland, S. and Mangeney, P., Eur. J. Org. Chem., 2000, 611.40 Alves, M. J., Carvalho, M. A., Proenca, M. F. J. R. P., and Booth, B. L., J. Heterocycl. Chem., 37,

1041 (2000).41 Manini, P., d’Ischia, M., Lanzetta, R., Parrilli, M., and Prota, G., Bioorg. Med. Chem., 7, 2525 (1999);

Chem. Abs., 132, 180751 (2000).42 Brighente, I. M. C., Menegatti, R., and Yunes, R. A., Int. J. Chem. Kinet., 32, 453 (2000).43 Atherton, J. H., Brown, K. H., and Crampton, M. R., J. Chem. Soc., Perkin Trans. 2, 2000, 941.44 Zhou, B., Guo, J., and Danishefsky, S. J., Tetrahedron Lett., 41, 2043 (2000).45 Bur, S. K. and Martin, S. F., Org. Lett., 2, 3445 (2000).


46 McClelland, R. A., Ren, D., D’Sa, R., and Ahmed, A. R., Can. J. Chem., 78, 1178 (2000).47 Jabin, I., Revial, G., Pfau, M., Decroix, B., and Netchitaielo, P., Org. Lett., 1, 1901 (1999); Chem. Abs.,

132, 63840 (2000).48 Nishitani, T., Shiraishi, H., Sakaguchi, S., and Ishii, Y, Tetrahedron Lett., 41, 3389 (2000).49 (a) Adams, J. P., J. Chem. Soc., Perkin Trans. 1, 2000, 125; (b) Adams, J. P., Contemp. Org. Synth., 4,

517 (1997).50 Levkovskaya, G. G., Drozdova, T. I., Rozentsveig, I. B., and Mirskova, A. N., Russ. Chem. Rev., 68,

581 (1999); Chem. Abs., 132, 107496 (2000).51 Ito, K. and Saito, K., Recent Res. Dev. Pure Appl. Chem., 3, 91 (1999); Chem. Abs., 133, 104977 (2000).52 Zhao, J., Xie, P., Chen, S. F., and Liang, X. T., Chin. Chem. Lett., 11, 475 (2000); Chem. Abs., 133,

237889 (2000).53 Sakamoto, T., Numata, A., and Kondo, Y., Chem. Pharm. Bull., 48, 669 (1999); Chem. Abs., 133,

30422 (2000).54 Lawande, S. P. and Arbad, B. R., J. Indian Chem. Soc., 77, 352 (2000); Chem. Abs., 133, 296104

(2000).55 Kamitani, A., Chatani, N., Morimoto, T., and Murai, S., J. Org. Chem., 65, 9230 (2000).56 Avdeenko, A. P. and Menafova, Y. V., Russ. J. Org. Chem., 36, 245 (2000); Chem. Abs., 133, 321685

(2000).57 Stadler, A. and Kappe, C. O., J. Chem. Soc., Perkin Trans. 2, 2000, 1363.58 Kozlov, A. P., Sazhnev, S. S., Kozlova, G. A., and Andreichikov, Y. S., Russ. J. Org. Chem., 36, 417

(2000); Chem. Abs., 133, 296105 (2000).59 El-Taher, M. A. E.-D., Pak. J. Sci. Ind. Res., 42, 78 (1999); Chem. Abs., 132, 63839 (2000).60 Ukaji, Y., Shimizu, Y., Kenmoku, Y., Ahmed, A., and Inomata, K., Bull. Chem. Soc. Jpn., 73, 447

(2000).61 Qian, C. and Wang, L., Tetrahedron, 56, 7193 (2000).62 Mohrle, H. and Jeandree, M., Z. Naturforsch., Teil B, 55, 74 (2000); Chem. Abs., 132, 250817 (2000).63 Terstegen, F., Carter, E. A., and Buss, V., Int. J. Quantum Chem., 75, 141 (1999); Chem. Abs., 132,

23104 (2000).64 Speckamp, W. N. and Moolenaar, M. J., Tetrahedron, 56, 3817 (2000).65 Miyabe, H., Ueda, M., and Naito, T., J. Org. Chem., 65, 5043 (2000).66 Miyabe, H., Ushiro, C., Ueda, M., Yamakawa, K., and Naito, T., J. Org. Chem., 65, 176 (2000).67 Malpica, A., Calzadilla, M., and Cordova, T., J. Phys. Org. Chem., 13, 162 (2000).68 More O’Ferrall, R. A., O’Brien, D. M., and Murphy, D. G., Can. J. Chem., 78, 1594 (2000).69 Garcia, B., Munoz, M. S., Ibeas, S., and Leal, J. M., J. Org. Chem., 65, 3781 (2000).70 Shastin, A. V., Korotchenko, V. N., Nenajdenko, V. G., and Balenkova, E. S., Tetrahedron, 56, 6557

(2000).71 Singh, S. P., Kumar, D., Batra, H., Naithani, R., Rozas, I., and Elguero, J., Can. J. Chem., 78, 1109

(2000).72 Miyata, O., Kimura, Y., and Naito, T., Chem. Commun. (Cambridge), 1999, 2429.73 Chandrasekhar, S., Venkat Reddy, M., Srinavasa Reddy, K., and Ramarao, C., Tetrahedron Lett., 41,

2667 (2000).74 Friestad, G. K. and Qin, J., J. Am. Chem. Soc., 122, 8329 (2000).75 Ulven, T. and Carlsen, P. H. J., Eur. J. Org. Chem., 2000, 3971.76 Mostaghim, R., Yangjeh, A. H., and Gholami, M. R., Indian J. Chem., Sect. B, 38, 976 (1999); Chem.

Abs., 132, 165827 (2000).77 Yanchuck, N. I., Ukr. Khim. Zh., 64, 51 (1999); Chem. Abs., 132, 12077 (2000).78 Blackmond, D. G., Acc. Chem. Res., 33, 402 (2000).79 Denmark, S. E. and Stavenger, R. A., Acc. Chem. Res., 33, 432 (2000).80 Denmark, S. E., Stavenger, R. A., Su, X., Wong, K.-T., and Nishigaichi, Y., in 12th Curr. Trends Org.

Synth. [Proc. Int. Conf.] (1998); (eds Scolastico, C. and Nicotra, F.), Kluwer/Plenum Publishers, NewYork 1999, p. 7; Chem. Abs., 133, 209580 (2000).

81 Soloshonok, V. A., Enantiocontrolled Synth. Fluoro-Org. Compd., 229 (1999); Chem. Abs., 132, 151319(2000).

82 Kuwano, R. and Ito, Y., in Comprehensive Asymmetric Catalysis I–III (Eds Jacobsen, E. N., Pfaltz, A.,and Yamamoto, H.), Springer, Berlin, 1999, Vol. 3, p. 1067; Chem. Abs., 132, 151298 (2000).

83 Szlosek, M. and Figadere, B., Angew. Chem., Int. Ed. Engl., 39, 1799 (2000).84 Hashemzadeh, M. and Howell, A. R., Tetrahedron Lett., 41, 1855 (2000).85 Hashemzadeh, M. and Howell, A. R., Tetrahedron Lett., 41, 1859 (2000).86 Mahrwald, R., Org. Lett., 2, 4011 (2000).


87 Bouillon, J.-P., Portella, C., Bouquant, J., and Humbel, S., J. Org. Chem., 65, 5823 (2000); Chem. Abs.,133, 281332 (2000).

88 Bouillon, J.-P. and Portella, C., Eur. J. Org. Chem., 1999, 1571.89 List, B., Lerner, R. A., and, Barbas, C. F., J. Am. Chem. Soc., 122, 2395 (2000).90 Galobardes, M., Gascon, M., Mena, M., Romea, P., Urpi, F., and Vilarrasa, Org. Lett., 2, 2599 (2000).91 Corey, E. J. and Choi, S., Tetrahedron Lett., 41, 2769 (2000).92 Juhl, K., Gathergood, N., and Jorgensen, K. A., Chem. Commun. (Cambridge), 2000, 2211.93 Huang, Y., Monatsh. Chem., 131, 521 (2000).94 Carreira, E. M., in Comprehensive Asymmetric Catalysis I–III (eds Jacobsen, E. N., Pfaltz, A., and

Yamamoto, H.), Springer, Berlin, 1999, Vol. 3, p. 997; Chem. Abs., 132, 151297 (2000).95 Tian, H.-Y., Chen, Y.-J., Wang, D., Zeng, C.-C., and Li, C.-J., Tetrahedron Lett., 41, 2529 (2000).96 Nagayama, S. and Kobayashi, S., J. Am. Chem. Soc., 122, 11531 (2000).97 Ishitani, H., Yamashita, Y., Shimizu, H., and Kobayashi, S., J. Am. Chem. Soc., 122, 5403 (2000).98 Taylor, S. J., Duffey, M. O., and Morken, J. P., J. Am. Chem. Soc., 122, 4528 (2000).99 Matsukawa, S., Okano, N., and Imamoto, T., Tetrahedron Lett., 41, 103 (2000).

100 Denmark, S. E. and Stavenger, R. A., J. Am. Chem. Soc., 122, 8837 (2000).101 Shibasaki, M. and Groger, H., in Comprehensive Asymmetric Catalysis I–III, (eds Jacobsen, E. N.,

Pfaltz, A., and Yamamoto, H.), Springer, Berlin, 1999, Vol. 3, p. 1075; Chem. Abs., 132, 151299(2000).

102 Jager, V., Ohrlein, R., Wehner, V., Poggendore, P., Steuer, B., Raczko, J., Griesser, H., Kiess, F.-M.,and Menzel, A., Enantiomer, 4, 205 (1999); Chem. Abs., 132, 64452 (2000).

103 Wade, P. A., Murray, J. K., Shah-Patel, S., Palfey, B. A., and Carroll, P. J., J. Org. Chem., 65, 7723(2000).

104 Caracoti, A. and Flowers, R. A., Tetrahedron Lett., 41, 3039 (2000).105 Casiraghi, G., Zanardi, F., Appendino, G., and Rassu, G., Chem. Rev., 100, 1929 (2000).106 Toratsu, C., Fujii, T., Suzuki, T., and Takai, K., Angew. Chem., Int. Ed. Engl., 39, 2725 (2000).107 Markovic, D., Hamersak, Z., Visnjevac, A., Kojic-Prodic, B., and Sunjic, V., Helv. Chim. Acta, 82, 603

(1999).108 Takasu, K., Ueno, M., and Ihara, M., Tetrahedron Lett., 41, 2145 (2000).109 Yasuda, M., Ohigashi, N., and Baba, A., Chem. Lett., 2000, 1266.110 Li, G., Wei, H.-X., Gao, J. J., and Caputo, T. D., Tetrahedron Lett., 41, 1 (2000).111 Yamada, Y. M. A. and Ikegami, S., Tetrahedron Lett., 41, 2165 (2000).112 Yang, K.-S. and Chen, K, Org. Lett., 2, 729 (2000).113 Kluger, R. and Moore, I. F., J. Am. Chem. Soc., 122, 6145 (2000).114 Jacob, K., Sigalov, M., Becker, J. Y., Ellern, A., and Khodorkovsky, V., Eur. J. Org. Chem., 2000,

2047.115 Enders, D. and Ullrich, E. C., Tetrahedron: Asymmetry, 11, 3861 (2000).116 Gasull, E. I., Silber, J. J., Blanco, S. E., Tomas, F., and Ferretti, F. H., THEOCHEM, 503, 131 (2000);

Chem. Abs., 133, 89124 (2000).117 Kanai, K., Wakabayashi, H., and Honda, T., Org. Lett., 2, 2549 (2000).118 Fukuzawa, S., Matsuzawa, H., and Yoshimitsu, S., J. Org. Chem., 65, 1702 (2000).119 Shibato, A., Itagaki, Y., Tayama, E., Hokke, Y., Asao, N., and Maruoka, K., Tetrahedron, 56, 5373

(2000).120 Vidari, G., Bonicelli, M. P., Anastasia, L., and Zanoni, G., Tetrahedron Lett., 41, 3471 (2000).121 Denmark, S. E. and Fu, J., J. Am. Chem. Soc., 122, 12021 (2000).122 (a) Ooi, T., Uraguchi, D., Kagushima, N., and Maruoka, K., J. Am. Chem. Soc., 120, 5327 (1998); (b)

Maruoka, K. and Ooi, T., Chem. Eur. J., 5, 829 (1999); (c) Ooi, T., Uraguchi, D., and Maruoka, K.,Tetrahedron Lett., 39, 8105 (1998); (d) Blackwell, J. M., Piers, W. E., and Parvez, M., Org. Lett., 2,695 (2000).

123 Chang, H.-M. and Cheng, C.-H., Org. Lett., 2, 3439 (2000).124 Cozzi, P. G., Tagliavini, E., and Umani-Ronchi, A., in 12th Curr. Trends Org. Synth. [Proc. Int. Conf.]

(1998) (eds Scolastico, C. and Nicotra, F.), Kluwer/Plenum Publishers, New York, 1999, p. 239; Chem.Abs., 132, 321883 (2000).

125 Krafft, M. E. and Procter, M. J., Tetrahedron Lett., 41, 1335 (2000).126 Loh, T.-P., Xu, J., Hu, Q.-Y., and Vittal, J. J., Tetrahedron: Asymmetry, 11, 1565 (2000).127 Fang, X., Watkin, J. G., and Warner, B. P., Tetrahedron Lett., 41, 447 (2000).128 Gajewski, J. J. and Ngernmeesri, P., Org. Lett., 2, 2813 (2000).129 Chao, I., Shih, J. H., and Wu, H.-J., J. Org. Chem., 65, 7523 (2000).130 Di Maio, G., Solito, G., Vari, M. R., and Vecchi, E., Tetrahedron, 56, 7237 (2000).


131 Di Vitta, C., de Arruda Campos, I. P., Farah, J. P. S., and Zukerman-Schpector, J., J. Chem. Soc.,Perkin Trans. 1, 2000, 3692.

132 Nakamura, S., Kaneeda, M., Ishihara, K., and Yamamoto, H., J. Am. Chem. Soc., 122, 8120 (2000).133 Dell’Erba, C., Gruttadauria, M., Mugnoli, A., Noto, R., Novi, M., Occhiucci, G., Petrillo, G., and

Spinelli, D., Tetrahedron, 56, 4565 (2000).134 Lee, I., Kim, C. K., Lee, I. Y., and Kim, C. K., J. Phys. Chem. A, 104, 6332 (2000).135 Chiang, Y., Kresge, A. J., and Zhu, Y., J. Am. Chem. Soc., 122, 9854 (2000).136 Guthrie, J. P. and Pitchko, V., J. Am. Chem. Soc., 122, 5520 (2000).137 Guthrie, J. P., J. Am. Chem. Soc., 122, 5529 (2000).138 Baikalova, L. V., Gavrilova, G. A., Chipanina, N. N., and Turchaninov, V. K., Russ. J. Gen. Chem.,

70, 436 (2000); Chem. Abs., 133, 296171 (2000).139 Balsells, J. and Walsh, P. J., J. Am. Chem. Soc., 122, 3250 (2000).140 Palmieri, G., Tetrahedron: Asymmetry, 11, 3361 (2000).141 Legrand, O., Brunel, J.-M., and Buono, G., Tetrahedron Lett., 41, 2105 (2000).142 Okanima, M., Yanada, R., and Ibuka, T., Tetrahedron Lett., 41, 1047 (2000).143 Vazquez, J., Pericas, M. A., Maseras, F., and Lledos, A., J. Org. Chem., 65, 7303 (2000).144 Goldfuss, B., Steigelmann, M., Khan, S. I., and Houk, K. N., J. Org. Chem., 65, 77 (2000).145 Rosner, T., Sears, P. J., Nugent, W. A., and Blackmond, D. G., Org. Lett., 2, 2511 (2000).146 Qian, C.-T., Gao, F.-F., and Sun, J., Tetrahedron: Asymmetry, 11, 1733 (2000).147 Hanyu, N., Aoki, T., Mino, T., Sakamoto, M., and Fujita, T., Tetrahedron: Asymmetry, 11, 2971 (2000).148 Kostova, K., Genov, M., Philipova, I., and Dimitrov, V., Tetrahedron: Asymmetry, 11, 3253 (2000).149 Shen, X., Guo, H., and Ding, K., Tetrahedron: Asymmetry, 11, 4321 (2000).150 Hanyu, N., Mino, T., Sakamoto, M., and Fujita, T., Tetrahedron Lett., 41, 4587 (2000).151 Bastin, S., Brocard, J., and Pelinski, L., Tetrahedron Lett., 41, 7303 (2000).152 Goldfuss, B., Steigelmann, M., and Rominger, F., Eur. J. Org. Chem., 2000, 1785.153 Prieto, O., Ramon, D. J., and Yus, M., Tetrahedron: Asymmetry, 11, 1629 (2000).154 Yang, W. K. and Cho, B. T., Tetrahedron: Asymmetry, 11, 2947 (2000).155 Tanji, S., Kodaka, Y., Ohno, A., Shibata, T., Sato, I., and Saoi, K., Tetrahedron: Asymmetry, 11, 4249

(2000).156 Huang, W.-S. and Pu, L., Tetrahedron Lett., 41, 145 (2000).157 Bolm, C., Hermanns, N., Hildebrand, J. P., and Muniz, K., Angew. Chem., Int. Ed. Engl., 39, 3465

(2000).158 Musser, C. A. and Richey, H. G., J. Org. Chem., 65, 7750 (2000).159 Chan, W. H., Lee, A. W. M., Xia, P. F., and Wong, W. Y., Tetrahedron Lett., 41, 5725 (2000).160 Gawley, R. E., in Grignard Reagents (ed. Richey, H. G.), Wiley, Chichester, 1999, p. 139; Chem. Abs.,

132, 334494 (2000).161 Saito, S., Shiozawa, M., Nagahara, T., Nakadai, M., and Yamamoto, H., J. Am. Chem. Soc., 122, 7847

(2000).162 Lu, J.-F., You, J.-S., and Gau, H.-M., Tetrahedron: Asymmetry, 11, 2531 (2000).163 Panev, S. and Dimitrov, V., Tetrahedron: Asymmetry, 11, 1517 (2000).164 Yasuda, M., Chiba, K., and Baba, A., J. Am. Chem. Soc., 122, 7549 (2000).165 Quan, L. G., Lamrani, M., and Yamamoto, Y., J. Am. Chem. Soc., 122, 4827 (2000).166 Gartner, P., Letschnig, M., and Knollmuller, M., Monatsh. Chem., 131, 867 (2000).167 Cainelli, G., Giacomini, D., Galletti, P., Orioli, P., and Paradisi, F., Eur. J. Org. Chem., 2000, 3619.168 Battagalia, A., Barbaro, G., Giorgianni, P., Guerrini, A., Bertucci, C., and Geremia, S., Chem. Eur. J.,

6, 3551 (2000).169 Fressigne, C., Maddaluno, J., Marquez, A., and Giessner-Prettre, C., J. Org. Chem., 65, 8899 (2000).170 Sun, X. and Collum, D. B., J. Am. Chem. Soc., 122, 2452 (2000).171 Sun, X. and Collum, D. B., J. Am. Chem. Soc., 122, 2459 (2000).172 Sun, C. and Williard, P. G., J. Am. Chem. Soc., 122, 7829 (2000).173 Hon, Y.-S. and Lee, C.-F., Tetrahedron, 56, 7893 (2000).174 Osman, F. H. and El-Samahy, F. A., Tetrahedron, 56, 1863 (2000).175 Schroder, U. and Berger, S., Eur. J. Org. Chem., 2000, 2601.176 Wang, Q., El Khoury, M., and Schlosser, M., Chem. Eur. J., 6, 420 (2000).177 Le Boulaire, V. and Gree, R., Chem. Commun. (Cambridge), 2000, 2195.178 Hafez, T. S., Henary, M. M., Refat, M., and Mahran, H., Phosphorus Sulfur Silicon Relat. Elem., 143,

33 (1999); Chem. Abs., 133, 43272 (2000).179 Yamataka, H., Rev. Heteroat. Chem., 21, 277 (1999); Chem. Abs., 132, 333997 (2000).180 Boulos, L. S., Shabana, R., and Shaker, Y. M., Heteroat. Chem., 11, 57 (2000); Chem. Abs., 132,

166277 (2000).


181 Perez, E. P. and Ortiz, F. L., Chem. Commun. (Cambridge), 2000, 2029.182 Yakout, E.-S. M. A., Giurgius, D. B., and Boulos, L. S., Phosphorus Sulfur Silicon Relat. Elem., 148,

177 (1999); Chem. Abs., 132, 22926 (2000).183 van Steenis, J. H., van Es, J. J. G. S. and van der Gen, A., Eur. J. Org. Chem., 2000, 2787.184 Lu, W. C., Sun, C. C., Zang, Q. J., and Liu, C. B., Chem. Phys. Lett, 311, 491 (1999); Chem. Abs.,

132, 22592 (2000).185 (a) Perozzi, E. F., Michalak, R. S., Figuly, J. D., Stevenson, W. H., Dess, D. B., Ross, M. R., and

Martin, J. C., J. Org. Chem., 46, 1049 (1981); (b) Kano, N., Hua, X. J., Kawa, S., and Kawashima, T.,Tetrahedron Lett., 41, 5237 (2000).

186 Bonini, C., Chiummiento, L., Funicello, and Spagnolo, P., Tetrahedron, 56, 1517 (2000).187 Shindo, M., Sato, Y., and Shishido, K., J. Org. Chem., 65, 5443 (2000).188 Tonder, J. E., Begtrup, M., Hansen, J. B., and Olesen, P. H., Tetrahedron, 56, 1139 (2000).189 Ando, K., Yuki Gosei Kagaku Kyokaishi, 58, 869 (2000); Chem. Abs., 133, 207396 (2000).190 Sano, S., Yakaguku Zasshi, 120, 432 (2000); Chem. Abs., 133, 58343 (2000).191 Kokin, K., Iitake, K.-I., Takaguchi, Y., Aoyama, H., Hayashi, S., and Motoyoshiya, J., Phosphorus Sul-

fur Silicon Relat. Elem., 133, 21 (1999); Chem. Abs., 133, 17555 (2000).192 Belokon, Y. N., Green, B., Ikonnikov, N. S., Larichev, V. S., Lokshin, B. V., Moscalenko, M. A.,

North, M., Orizu, C., Peregudov, A. S., and Timofeeva, G. I., Eur. J. Org. Chem., 2000, 2655.193 Kruckok, I. S., Gerus, I. I., and Kukhar, V. P., Tetrahedron, 56, 6533 (2000).194 Holmes, I. P. and Kagan, H. B., Tetrahedron Lett., 41, 7453 (2000).195 Holmes, I. P. and Kagan, H. B., Tetrahedron Lett., 41, 7457 (2000).196 Myers, A. G., Kung, D. W., and Zhong, B., J. Am. Chem. Soc., 122, 3236 (2000).197 Berthiaume, D. and Poirier, D., Tetrahedron, 56, 5995 (2000).198 Ward, D. E., Hrapchak, M. J., and Sales, M., Org. Lett., 2, 60 (2000).199 Yadav, J. S., Subba Reddy, B. V., and Prabhakar Rao, T., Tetrahedron Lett., 41, 7943 (2000).200 (a) Folleas, B., Marek, I., Normant, J.-F., and Saint-Jalmes, L., Tetrahedron, 56, 275 (2000); (b) Mur-

ray, B. A., in Organic Reaction Mechanisms 1998 (ed. Knipe, A. C. and Watts, W. E.), Wiley, Chich-ester, 2002, p. 20); (c) Mispelaere, C. and Roques, N., Tetrahedron Lett., 40, 6411 (1999).

201 Singh, R. P. and Shreeve, J. M., Tetrahedron, 56, 7613 (2000).202 Enders, D. and Breuer, K., in Comprehensive Asymmetric Catalysis I–III (eds Jacobsen, E. N.,

Pfaltz, A., and Yamamoto, H.), Springer, Berlin, 1999, Vol. 3, p. 1093; Chem. Abs., 132, 151300(2000).

203 Zhou, Y.-G., Li, A.-H., Dai, L.-X., and Hou, X.-L., Huaxue Xuebao, 58, 473 (2000); Chem. Abs., 133,43559 (2000).

204 Yang, X.-F. and Li, C.-J., Tetrahedron Lett., 41, 1321 (2000).205 Garcia Ruano, J. L., Barros, D., Carmen Maestro, M., Martin Castro, A. M., and Raithby, P. R., Tetra-

hedron: Asymmetry, 11, 4385 (2000).206 Hentemann, M. F., Allen, J. G., and Danishefsky, S. J., Angew. Chem., Int. Ed. Engl., 39, 1937 (2000).207 Jorgensen, K. A., Angew. Chem., Int. Ed. Engl., 39, 3558 (2000).208 Li, G. M., Niu, S., Segi, M., Tanaka, K., Nakajima, T., Zingaro, R. A., Reibenspies, J. H., and Hall, M.

B., J. Org. Chem., 65, 6601 (2000).209 Kabalka, G. W., Wu, Z., Trotman, S. E., and Gao, X., Org. Lett., 2, 255 (2000).210 Baines, K. M., Dixon, C. E., and Samuel, M. S., Phosphorus Sulfur Silicon Relat. Elem., 35, 953 (1999);

Chem. Abs., 132, 78592 (2000).211 Gerbst, A. G., Krylova, I. V., and Tsvetkov, D. E., Russ. J. Org. Chem., 35, 1662 (1999); Chem. Abs.,

132, 334093 (2000).212 Li, J., Sun, C., Liu, S., Feng, S., and Feng, D., Sci. China, Ser. B: Chem., 43, 240 (2000); Chem. Abs.,

133, 251931 (2000).213 Liu, H., Zhang, Y., and Yang, W., J. Am. Chem. Soc., 122, 6560 (2000).214 Mishima, M., Mustanir, Eventova, I., and Rappoport, Z., J. Chem. Soc., Perkin Trans. 2, 2000, 1505.215 Tupitsyn, I. F., Popov, A. S., Zatsepina, N. N., and Kaufman, V. Z., Russ. J. Gen. Chem., 70, 247

(2000); Chem. Abs., 133, 296166 (2000).216 Behnam, S. M., Behnam, S. E., Ando, K., Green, N. S., and Houk, K. N., J. Org. Chem., 65, 8970

(2000).217 Fontana, A., De Maria, P., Siani, G., Pierini, M., Cerritelli, S., and Ballini, R., Eur. J. Org. Chem.,

2000, 1641.218 Lammertsma, K. and Bharatam, P. V., J. Org. Chem., 65, 4662 (2000).219 Bharatam, P. V., Indian J. Chem., Sect. A, 39, 100 (2000); Chem. Abs., 133, 89090 (2000).220 Zou, J.-W., Li, J.-B., Zhu, L.-G., Yu, Q.-S., and Lin, R.-S., Gaodeng Xuexiao Huaxue Xuebao, 20, 1784

(1999); Chem. Abs., 132, 78260 (2000).


221 Delchev, V. B. and Nikolov, G. S., Monatsh. Chem., 131, 99 (2000).222 Bachrach, S. M. and Bapat, A., Internet J. Chem., 2, http://www.ijc.com/articles/1999v2/13/ (1999);

Chem. Abs., 132, 23019 (2000).223 Sobolewski, A. L. and Domcke, W., Chem. Phys. Lett., 310, 548 (1999); Chem. Abs., 131, 336635

(1999).224 Redington, R. L., J. Chem. Phys., 113, 2319 (2000); Chem. Abs., 133, 207458 (2000).225 Ye, S., Yunnan Daxue Xuebao, Ziran Kexueban, 21, 260 (1999); Chem. Abs., 132, 334100 (2000).226 Ivanov, Y. V., Vovna, V. I., and Lvov, I. B., J. Struct. Chem., 40, 192 (1999); Chem. Abs., 132, 49644

(2000).227 Li, Y.-H. and Xu, K.-Y., Jiangxi Shifan Daxue Xuebao, Ziran Kexueban, 23, 99 (1999); Chem. Abs.,

132, 49677 (2000).228 Nicola, T., Vieser, R., and Eberbach, W., Eur. J. Org. Chem., 2000, 527.229 Wladislaw, B., Bjorklund, M. B., Marzorati, L., and Zukerman-Schpector, J., Phosphorus Sulfur Silicon

Relat. Elem., 157, 139 (1999); Chem. Abs., 133, 17118 (2000).230 Andrieux, C. P., Saveant, J.-M., and Tardy, C., J. Electroanal. Chem., 476, 81 (1999); Chem. Abs., 132,

56080 (2000).231 Taylor, S. K., Tetrahedron, 56, 1149 (2000).232 Yamashita, Y., Emura, Y., Odashima, K., and Koga, K., Tetrahedron Lett., 41, 209 (2000).233 Busch-Petersen, J. and Corey, E. J., Tetrahedron Lett., 41, 6941 (2000).234 Vedejs, E., Kruger, A. W., Lee, N., Sakata, S. T., Stec, M., and Suna, E., J. Am. Chem. Soc., 122, 4602

(2000).235 Ramakrishnan, P. S. and Nambi, K., J. Indian Chem. Soc., 77, 232 (2000); Chem. Abs., 133, 58404

(2000).236 Anitha, N., Rangappa, K. S., and Rai, K. M. L., Indian J. Chem., Sect. B, 38, 1046 (1999); Chem. Abs.,

132, 208016 (2000).237 Fadnis, A. G. and Arzare, S., Oxid. Commun., 23, 50 (2000); Chem. Abs., 133, 74191 (2000).238 Mayanna, S. M. and Gowda, C. C., Oxid. Commun., 23, 34 (2000); Chem. Abs., 133, 74214 (2000).239 Singh, A. K., Rahmani, S., Singh, V., Gupta, V., and Singh, B., Oxid. Commun., 23, 55 (2000); Chem.

Abs., 133, 74192 (2000).240 Gupta, N., Chaurasia, N., Singh, V., and Singh, A. K., Oxid. Commun., 23, 42 (2000); Chem. Abs.,

133, 74215 (2000).241 Kambo, N. and Upadhyay, S. K., Transition Met. Chem. (Dordrecht, Neth.), 25, 461 (2000); Chem.

Abs., 133, 177363 (2000).242 Wang, Y., Chackalamannil, S., and Aube, J., J. Org. Chem., 65, 5120 (2000).243 Rajkumar, C. and Kannan, P. S. M., Orient. J. Chem., 15, 573 (1999); Chem. Abs., 132, 236706 (2000).244 Lehtinen, C., Nevalainen, V., and Brunow, G., Tetrahedron, 56, 9375 (2000).245 Gangwani, H., Sharma, P. K., and Banerji, K. K., Int. J. Chem. Kinet., 32, 615 (2000).246 Revathi, S. K., Rangaswamy, and Ananda, S., Asian J. Chem., 11, 1271 (1999); Chem. Abs., 132,

250828 (2000).247 Balasubramanian, K., Lakshmanan, K., and Sekar, K. G., Asian J. Chem., 11, 1451 (1999); Chem. Abs.,

132, 250830 (2000).248 Agrawal, G. L. and Jain, R., Oxid. Commun., 22, 514 (1999); Chem. Abs., 132, 222159 (2000).249 Fedevich, O. E., Levush, S. S., and Kit, Y. V., Theor. Exp. Chem., 35, 301 (1999); Chem. Abs., 132,

264826 (2000).250 Gowda, B. T. and Moodithaya, B. S., J. Indian Chem. Soc., 77, 194 (1999); Chem. Abs., 133, 43129

(2000).251 Won, S.-J., Ryu, J.-C., Bae, J.-H., Kim, Y.-D., and Kang, J.-G., Bull. Korean Chem. Soc., 21, 487

(2000); Chem. Abs., 133, 73710 (2000).252 Jaky, M., Szammer, J., and Simon-Trompler, E., J. Chem. Soc., Perkin Trans. 2, 2000, 1597.253 Tibi, S. and Koppenol, W. H., Helv. Chim. Acta, 82, 2412 (1999).254 Jarboe, S. G. and Beak, P., Org. Lett., 3667 (1999); Chem. Abs., 132, 207714 (2000).255 Nazarov, A. M., Yamilova, G. A., and Komissarov, V. D., Russ. Chem. Bull., 49, 654 (2000); Chem.

Abs., 133, 222238 (2000).256 Gopinath, R. and Patel, B. K., Org. Lett., 2, 577 (2000).257 Zhu, S., Pardi, S., and Cohen, T., Tetrahedron Lett., 41, 9589 (2000).258 Suwa, T., Nishino, K., Miyatake, M., Shibata, I., and Baba, A., Tetrahedron Lett., 41, 3403 (2000).259 Aramini, A., Brinchi, L., Germani, R., and Savelli, G., Eur. J. Org. Chem., 2000, 1793.260 Bryson, T. A., Jennings, J. M., and Gibson, J. M., Tetrahedron Lett., 41, 3523 (2000).261 Yu, H.-T., Kang, R.-H., and Ou, Y.-M., Youji Huaxue, 20, 441 (2000); Chem. Abs., 133, 309541 (2000).262 Tomoda, S., Kaneno, D., and Senju, T., Heterocycles, 52, 1435 (1999); Chem. Abs., 132, 334042 (2000).


263 Tomoda, S., Kaneno, D., and Senju, T., Chem. Lett., 1999, 1161; Chem. Abs., 132, 63818 (2000).264 Jimenez-Cruz, F., Cetina, R., and Rios-Olivares, H., Chem. Lett., 2000, 956.265 Clayden, J., Westlund, N., Beddoes, R. L., and Helliwell, M., J. Chem. Soc., Perkin Trans. 1, 2000,

1351.266 Clayden, J., McCarthy, C., Westlund, N., and Frampton, C. S., J. Chem. Soc., Perkin Trans. 1, 2000,

1363.267 Clayden, J., Westlund, N., and Frampton, C. S., J. Chem. Soc., Perkin Trans. 1, 2000, 1379.268 Bartoli, G., Bellucci, M. C., Bosco, M., Dalpozzo, R., Marcantoni, E., and Sambri, L., Chem. Eur. J.,

6, 2590 (2000).269 Keck, G. E. and Wager, C. A., Org. Lett., 2, 2307 (2000).270 Ballini, R., Bosica, G., Marcantoni, E., Vita, P., and Bartoli, G., J. Org. Chem., 65, 5854 (2000).271 Bataille, P., Paterne, M., and Brown, E., Tetrahedron: Asymmetry, 11, 1165 (2000).272 Node, M., Nishide, K., Shigeta, Y., Shiraki, H., and Obata, K., J. Am. Chem. Soc., 122, 1927 (2000).273 Rogic, M. M., J. Org. Chem., 65, 6868 (2000).274 Muller, P., Nury, P., and Bernardinelli, G., Helv. Chim. Acta, 82, 843 (1999).275 Brunel, J. M., Legrand, O., and Buono, G., Eur. J. Org. Chem., 2000, 3313.276 Zhao, J., Bao, X., Liu, X., Wan, B., Han, X., Yang, C., Hang, J., Feng, Y., and Jiang, B., Tetrahedron:

Asymmetry, 11, 3351 (2000).277 Li, M., Xie, R., Tian, S., and Tian, A., Int. J. Quantum, Chem., 78, 252 (2000); Chem. Abs., 133, 296072

(2000).278 Santhi, V. and Madhusadana Rao, J., Tetrahedron: Asymmetry, 11, 3553 (2000).279 Liu, X., Zhu, T., and Bao, M., Wuxi Qinggong Daxue Xuebao, 18, 94 (1999); Chem. Abs., 132, 92936

(2000).280 Yamada, I. and Noyori, R., Org. Lett., 2, 3425 (2000).281 Ramachandran, P. V. and Brown, H. C., Enantiocontrolled Synth. Fluoro-Org. Compd., 1999, 179;

Chem. Abs., 132, 151318 (2000).282 Solladie-Cavallo, A., Bouerat, L., and Roje, M., Tetrahedron Lett., 41, 7309 (2000).283 Liu, X. and Verkade, J. G., J. Org. Chem., 65, 4560 (2000).284 Guiral, V., Delbecq, F., and Sautet, P., Organometallics, 19, 1589 (1999); Chem. Abs., 132, 321966

(2000).285 Santosh Laxmi, Y. R. and Backvall, J.-E., Chem. Commun. (Cambridge), 2000, 611.286 Murray, A. P. and Chopa, A. B., Molecules [online computer file], 5, 388 (2000), http://www.mdpi.org/

molecules/papers/50300252.pdf; Chem. Abs., 133, 207952 (2000).287 Banik, B. K., Zegrocka, O., and Becker, F. F., J. Chem. Res. (S), 2000, 321.288 Kabwalka, G. W. and Wu, Z., Tetrahedron Lett., 41, 579 (2000).289 (a) Kabalka, G. W., Wu, Z., Trotman, S. E., and Gao, X., Org. Lett., 2, 255 (2000); (b) Kabalka, G. W.,

Wu, Z., and Ju, Y., Tetrahedron Lett., 41, 5161 (2000); (c) Corre, M. L., Gheerbrant, E., and Deit, H. L.,J. Chem. Soc., Chem. Commun., 1989, 3131; (d) Aizpurua, J. M. and Palomo, C., Tetrahedron Lett.,25, 1103 (1984).

290 Notario, A., Mellouki, A., and Le Bras, G., Int. J. Chem. Kinet., 32, 62 (2000).291 Papagni, C., Arey, J., and Atkinson, R., Int. J. Chem. Kinet., 32, 79 (2000).292 Ullerstam, M., Langer, S., and Ljungstrom, E., Int. J. Chem. Kinet., 32, 294 (2000).293 Thevenet, R., Mellouki, A., and Le Bras, G., Int. J. Chem. Kinet., 32, 676 (2000).294 Ramacher, B., Orlando, J. J., and Tyndall, G. S., Int. J. Chem. Kinet., 32, 460 (2000).295 Beukes, J. A., D’Anna, B., Bakken, V., and Nielsen, C. J., Phys. Chem. Chem. Phys., 2, 4049 (2000).296 Xia, W. S. and Lin, M. C., Phys. Chem. Chem. Phys., 2, 5566 (2000).297 Choi, Y. M., Xia, W. S., Park, J., and Lin, M. C., J. Phys. Chem. A, 104, 7030 (2000).298 Gierczak, T. and Ravishankara, A. R., Int. J. Chem. Kinet., 32, 573 (2000).299 Leblanc, D., Audier, H. E., and Denhez, J. P., J. Mass Spectrom., 34, 969 (1999); Chem. Abs., 132,

12348 (2000).300 Armelin, E. A., Donate, P. M., and Galembeck, S. E., Tetrahedron, 56, 5105 (2000).301 Huisgen, R., Kalvinsch, I., Li, X., and Mloston, G., Eur. J. Org. Chem., 2000, 1685.302 Huisgen, R., Li, X., and Mloston, G., and Fulka, C., Eur. J. Org. Chem., 2000, 1695.303 Furukawa, I., Sasaki, M., Inoue, T., and Ohta, T., Phosphorus Sulfur Silicon Relat. Elem., 143, 85

(2000); Chem. Abs., 133, 58579 (2000).304 Majo, V. J., Anand, R. V., and Perumal, P. T., Indian J. Chem., Sect. B, 38B, 763 (1999); Chem. Abs.,

132, 49767 (2000).305 Aggarwal, V. K., de Vicente, J., Pelotier, B., Holmes, I. P., and Bonnert, R. V., Tetrahedron Lett., 41,

10327 (2000).306 Angle, S. R. and Neitzel, M. L., J. Org. Chem., 65, 6458 (2000).


307 Fox, J. M., Huang, X., Chieffi, A., and Buchwald, S. L., J. Am. Chem. Soc., 122, 1360 (2000).308 Stavber, S., Jereb, M., and Zupan, M., Chem. Commun. (Cambridge), 2000, 1323.309 Moillet, J. S., Fluorinated Bioact. Compd. Agric. Med. Fields [Proc. Conf.], 21, 1 (1999), Chemical &

Polymer, Hemel Hemstead; Chem. Abs., 132, 333971 (2000).310 Kuroda, C. and Koshio, H., Chem. Lett., 2000, 962.311 D’Auria, M., Racioppi, R., and Romaniello, G., Eur. J. Org. Chem., 2000, 3265.312 Bohm, C., Schinnerl, M., Bubert, C., Zabel, M., Labahn, T., Parisini, E., and Reiser, O., Eur. J. Org.

Chem., 2000, 2955.313 Braverman, S., Cherkinsky, M., Suresh Kumar, E. V. K., and Gottlieb, H. E., Tetrahedron, 56, 4521

(2000).314 Isaev, S. D., Novikova, M. I., Chizhov, O. S., Shchrbakov, M. V., Shishkin, O. V., and Yurchenko, A.

G., Ukr. Khim. Zh., 65, 137 (1999); Chem. Abs., 132, 265039 (2000).315 Zanatta, N., Madruga, C. da C., Marisco, P. da C., Flores, D. C., Bonacorso, H. G., and Martins, M.

A. P., J. Heterocycl. Chem., 37, 1213 (2000).316 Hamed, O., El-Qisairi, A., and Henry, P. M., Tetrahedron Lett., 41, 3021 (2000).317 Degueil-Castaing, M., Moutet, L., and Maillard, B., J. Org. Chem., 65, 3961 (2000).318 Borisov, I. M. and Gerchikov, A. Y., Neftekhimiya, 40, 46 (2000); Chem. Abs., 133, 192848 (2000).319 Fujioka, H., Kotoku, N., Nagatomi, Y., and Kita, Y., Tetrahedron Lett., 41, 1829 (2000).320 Smith, B. T., Gracias, V., and Aube, J., J. Org. Chem., 65, 3771 (2000).321 Koh, H. J., Han, K. L., Lee, H. W., and Lee, I., J. Org. Chem., 65, 4706 (2000).322 Proctor, G. R. and Harvey, A. L., Curr. Med. Chem, 7, 295 (1999); Chem. Abs., 132, 308521 (2000).323 Sano, S., Yakugaku Zasshi, 120, 28 (2000); Chem. Abs., 132, 194608 (2000).

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