CHAPTER 4: ELECTRON TRANSFER INITIATED REACTIONS€¦ · CHAPTER 4: ELECTRON TRANSFER INITIATED...

ORGANIC REACTIVITY - CHEM*4720 - COURSE NOTES W2012

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CHAPTER 4: ELECTRON TRANSFER INITIATED REACTIONS

1- Grimshaw, J. Electrochemical reactions and mechanisms in organic chemistry.

Elsevier, New York, 2000.

2- Nelsen S. F. Electron Transfer in Organic Chemistry. In Electron Transfer Chemistry.

Balzani, V. (Ed.) Vol. 1, 2001.

3- Schäfer, H. J. Organic Electrochemistry. In Encylopedia of Electrochemistry. Vol 8.

Wiley-VCH, Weinheim, 2004.

4- Torii, S. Electroorganic Reduction Synthesis. Wiley-VCH, Weinheim, 2006.

5- Savéant, J.-M. Elements of Molecular and Biomolecular Electrochemistry. An

Electrochemical Approach to Electron Transfer Chemistry. Wiley & Sons, Inc., Hoboken,

New Jersey, 2006.

6- Evans, D. H.; O’Connell, K. M. Conformation Changes and Isomerizations Associated

with Electrode Reactions. In Electroanalytical Chemistry, Bard, A. J., Ed., Marcel

Dekker: New York, 1985, Vol. 14, pp.113-207.

7- Eberson, L. Electron Transfer in Organic Chemistry. In Advances in Physical Organic

Chemistry; Gold V. and Bethell D. Eds.; Academic press, London, 1982. vol. 18, pp. 78-

185.

8- Houmam A. Electron Transfer Initiated Reactions: Bond Formation and Bond

Dissociation, Chem. Rev. 2008, 128, pp. 2180-2237.


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Electron transfer reactions are among the most elementary of all chemical reactions and

play a fundamental role in many areas including organic synthesis, biological processes,

novel energy sources, energy storage devices, amperometric sensors, etc. A field that

has attracted considerable attention is that involving electron transfer to organic and

bioorganic molecules.

Electron transfer reactions can be initiated using electrochemistry (an electrode),

photochemistry, or an electron donor (reducing) or acceptor (oxidizing) compound.

The first electroorganic synthesis was performed by Michael Faraday (1843). It was the

anodic decarboxylation of acetic acid in aqueous medium, and the formation of ethane

via creation of a new carbon-carbon bond:

2 CH3COO CH3CH3 + 2CO2-2e-

Pt

Henry Kolbe (1849) electrolyzed fatty acids and half-esters of dicarboxylic acids and

established the practical basis of electroorganic synthesis. Near the end of the 19th

century various electrolytic industrial processes emerged, mostly reductive, stimulated

by pioneering works of Kolbe, Haber, Fitcher, Tafel and other notable contemporaries

who expanded the foundation of organic electrochemical technology.

Great progress in the understanding of fundamental mechanisms of electrochemical

reactions has been achieved during the last few decades in parallel with the spectacular

advances of electroanalytical and spectroanalytical methodologies and the commercial

availability of the relevant instruments. This is the reason why dynamics and

mechanisms of ET initiated reactions are well understood compared to “traditional”

organic synthetic reactions.


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I. ET INITIATED REACTIONS

A wide variety of chemical transformations that are initiated by a single initial electron

transfer are described in the literature and can be encountered under both oxidative and

reductive conditions

ET initiated reduction of functional group

Ex. 1: Hydrogenation of multiple C-C bonds can proceed indirectly, electrocatalytically,

or by a direct electron transfer to the multiple bond. The reaction can proceed with good

selectivity.

COOH COOH

+ 2e-

Ex. 2: Reductive dehalogenation (also very selective).

Cl

Br

O

Cl

H

O

+ 2e-, Et4NBr

DMF 96%

Ex. 3: Electrochemical reduction of nitroaromatics. High yields of amines are obtained in

the reduction of nitroaromatics carrying a group in the para position which prevents a

rearrangement.

NH2

CO2H

NH2

Me

NO2

R

R = Me, + 6e-

(Pb), H2SO4

R = CO2H, + 6e-

(Pb), HCl

92% 100%


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ET induced substitution

ET generated anionic intermediates can react with “electrophiles” to yield substitution products. Example: Electrochemical alkylation and acylation can be achieved when alkylating or acylating agents (usually: anhydrides, halogenides of acids, their nitriles and DMF) are present in the reductive process of a convenient substrate. a)

S S S

O

2 e-, DMF

Ac2O 90%

b)

Br

CCl3

O

H BrO

Cl Cl

O

Cl

Cl

2 e-, LiClO4

DMF+

- Br 40%

c) Remember SRN1 reactions?

Reductive Eliminations

The cathodic reduction of the geminal polyhalogeno derivatives in he absence of both

electrophiles and protons donors results in the formation of a carbanion that is stabilized

by splitting off a further halogenide ions which in the presence of a sufficiently

“nucleophilic” alkene adds on to the double bond and forms gem-

dihalogenocyclopropanes.


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Ex. 1: Electrosynthesis of 1,1-dichlorotrimethylcyclopropane from tetrachloromethane.

MeMe

Me

Cl Cl

Me

H

Me

MeCCl2 Cl CCl2+2 e-, -2Cl

CH3Cl-ClCCl4 82%

Ex. 2: Electrosynthesis of gem-difluorocyclopropane derivatives from

dibromodifluoromethane.

+2e-, -2Br

CH2Cl2CF2Br2 CF2

Me

Ph

F F

Ph

Me57%

Ex. 3: Electroreduction of vic-dihalogeno derivatives undergo a stereospecific trans-

elimination to yield an alkene. This can be used for the synthesis of alkenes with strong

internal stress, usually isolated as cycloaddition products of a reaction with dienes.

Br

Cl

+2e-, Et4NBF4

DMF100%

Oxidation of alkanes Alkanes are functionalized by anodic oxidation in acetonitrile, methanol, acetic acid and

more acidic solvents such as trifluoroacetic acid and fluorosulphuric acid. Reaction

requires very positive electrode potentials and platinum has generally been used as

anode in laboratory scale experiments.


5- 6

The first stage of these reactions involves the removal of an electron from either a

carbon-hydrogen or a carbon-carbon -bond, with simultaneous bond cleavage to yield

the most stable carbon radical and carbonium anion. These are dissociative processes

where the radical cation cannot be detected as an intermediate.

In acetonitrile, carbon ions combine with the solvent to form a nitrilium ion. The latter

reacts with added water to form the N-substituted acetamide, often in good yields

(introduction of an amino-substituent.

R

NHCOCH 3

R NHCOCH 3

1) Pt anode,

CH3CN, LiClO4

2) H2O

R

Et

iPr

tBu

CO2CH3

%yield

0

9

62

64

%yield

77

75

7

0

In acetic acid and trifluoroacetic acid, the carbonium ion is quenched by reaction with

the carboxylate anion. Electrochemical oxidation in these solvents is a route for the

introduction of a hydroxyl substituent.

Electrochemical oxidation of haloalkanes Oxidation of alkyl bromides and iodides leads to loss of a non-bonding electron from the

halogen substituent, followed by cleavage of the carbon-halogen bond to form a

carbonium ion and a halogen atom. The products isolated are formed by further

reactions of the carbonium ion while two halogen atoms combine to form the halogen

molecule. In acetonitrile, the carbonium ion reacts with a solvent molecule to form a

nitrollium ion. The latter is quenched with water to give the N-alkylacetamide.


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Ex1:

CH2IPt anode

CH3CN, LiClO4

CH3

NHCOCH 3

Ex2:

CH2I

I

Pt anode

CH3CN, LiClO4

Pt anode

CH3CN, LiClO4

CH2NHCOCH 3

NHCOCH 3

+

10%

90%

Oxidative dimerization of alkenes.

DDD

DD

D

D

D

Nu

Nu

or (A,-e-)

A

A

- 2H

+ 2Nu

- e-

D = EDG (OR, Ph, NHCOR, OSiMe3, ...)

Oxidative cycloaddition of alkenes.

Olefins also undergo cycloaddition reactions through a similar mechanism involving the

formation of a new chemical bond in a step subsequent to the ET oxidation.

DD

A

ADD

DD

+ e-- e-


5- 8

An interesting example: Reaction of Levoglucosenone in the presence of

electrogenerated superoxide anion

In ET initiated reactions it is possible to control the stereoselectivity by changing (i) the

concentration of the reagents, (ii) the current density (or potential), (iii) the added

reagents, or (iv) the reactions conditions.


5- 9

II. INITIATION MODES AND EXPERIMENTAL METHODOLOGIES

A very important aspect of ET reactions is that they can be initiated by a variety of

procedures. These include thermal (homogeneous and heterogeneous),

photochemical and through use of solvated electrons as in pulse radioysis. This has

stimulated the development of a wide range of techniques and analytical methodologies

for the study of ET reactions with a view to gaining insights into various aspects of their

dynamics and mechanisms. All these techniques have an obvious common factor: the

addition or removal of an electron to or from a reactant. But the fact that their similarity

may end here means that sometimes these techniques provide different information

regarding such ET transfer-initiated reactions. They differ in terms of the analysis

time windows thus making them useful for different systems and capable of studying

different types of intermediates. The other issue concerns the fact that the initiation step

itself, as well as subsequent steps may differ from one initiation technique to another

despite the fact that in all cases an electron is added or removed. As a result the

chemistry following the initial ET step may differ totally from one initiation mode

to another. So while thermal homogenous initiation is a reaction usually leading to

the transfer of a single electron, electrochemical initiation is a heterogeneous

process very often involving the transfer of multiple electrons. Photoinduced

electron transfer involves reactants in the excited state and therefore differs from

both the homogeneous thermal as well as the electrochemical heterogeneous cases.

Pulse radiolysis is different again in the sense that it generates solvated electrons

and strong oxidizing and reducing agents, and the ET initiation is usually subject to a

large standard free energy. An aspect where these initiation modes do not present the

same value is ET-initiated organic synthesis. It is nevertheless possible, when all these

factors are taken into consideration, to acquire complementary information regarding the

nature of the ET process and its kinetics with respect to the chemical step that follows

through use of different initiation modes.

We will only briefly describe cyclic voltammetry because of its crucial importance in

gaining dynamic and mechanistic information.


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Cyclic Voltammetry: A very important tool for studying electron transfer initiated

reactions. It provides information regarding the kinetics, the thermodynamics and the

mechanisms of the investigated reactions.

Important characteristics:

- Peak Potential

- Number of electrons exchanged per molecule (n)

- Transfer coefficient

Potential (mV)

Time(s)E1

E2

Reversible System

-E

i

B + CA + e- A.-

D

Ek1 k2

k3+e-

k4

workstation

RECE WE

Irreversible System

-E

i


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Let’s look at the following example involving the electrochemical reduction of arylazo

sulfides

- The electrochemical reduction of aryl azosulfides yields the corresponding sulfides

and decompositions products.

- The mechanism of the global reaction is an SRN1 mechanism.

Ar-X + e-

Ar-X

Ar + Nu

ArNu + Ar-X

Ar-X

Ar + X

ArNu

ArNu + Ar-X

k

The following Figure shows the Cyclic voltammogram of paracyano phenyl azo phenylsulfide

(c=1mM) in ACN + 0.1M NBu4ClO4 on a glassy carbon electrode.

N N SNC

NC H

NC S

The mechanism of the reaction can be written as per the following scheme.


5- 12

Adding increasing amounts of cyanide during the electrochemical investigation of the

arylazo compound induces important changes to cyclic voltammogram. The first

reduction peak decreases while a new reduction peak appears. This new peak is due to

the reduction of the newly formed terephtalonitrile (NCC6H4CN).

NC CN

Cyclic voltammogram of

paracyano phenyl azo

phenylsulfide (c=1mM)

in CH3CN + 0.1M

NBu4ClO4 on a glassy

carbon electrode

(a) [CN-] = 0 mM, …

(b) [CN-] = 10 mM, - - -

(c) [CN-] = 320 mM, ____


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The global mechanism is:

The kinetics of the reaction of the cyanide nucleophile were thus calculated in two

solvents (CH3CN and DMSO) and shown a slight dependence of the solvent’s viscosity.

k= 1,5 1011 M-1s-1 in CAN and 2,4 1011 M-1s-1 in DMSO

- Understanding ET reactions (outer sphere ET vs dissociative ET)

- Structure dependence:

- Representative examples

NNC N S

NNC N S

NC SN2+ +-

SNCNC

+ e-

A

+ CN

NC SNCCN

+ A

+

-

CN

+ A

+ AA

.

-.

-.-.

-.

-.

-.


5- 14

III. ET reactions (outer sphere ET vs dissociative ET)

Unravelling the nature of the fundamental steps involved in the electron transfer and the

subsequent reactions has always been an essential step towards reaching a molecular

understanding of ET processes. In these multiple step reactions important questions

arise not only concerning their mechanisms and the factors controlling them but also the

associated energies and kinetics and any similarity to certain non-electron transfer

processes. Extensive studies have already shed considerable new light on many of

these important questions.

Outer sphere electron transfer:

Certain organic chemical compounds can accept or loose an electron without

undergoing considerable structural changes (bond cleavage or formation). These

electron transfer reactions are usually associated with only some reorganization and are

called “outer sphere” ET reactions.

For example, the electron transfer to nitrobenzene leads to the corresponding radical

anion. Nitrobenzene is able to host the incoming electron without undergoing any bond

dissociation.

NO2NO2+ e-

The nitrobenzene shows a totally reversible cyclic voltammogram indicating the stability

of both the neutral and the reduced forms.

Chemistry consuming the resulting radical anion can still be initiated by adding

various reagents.

Example: Oxidative formation of C-S bond in the synthesis of thianthrenium salts.


5- 15

Ar

O

OH

Ar

Th+

OH

Ar

Th+

+

O

Ar

Th+

R4

R2

R3

R1

R4

R2

R3

R1

Th+

R3

R1

Th

R2

R4

Th+ +Th

-H+

Th

S

S

-e-

For many other organic chemical compounds the addition (or removal) of an electron will

induce more important structural changes (usually a bond dissociation). Alkyl halides for

example undergo the dissociation of the C-halogen chemical bond.

Br + e- + Br

In cyclic voltammetry these compounds show an irreversible cyclic voltammogram. The

example below is that of Bromoadamantane in acdtonitrile on a glassy carbon electrode.

Ep = -2.30V

n = 2e- /molecule

= 0.3

Important: An irreversible

cyclic voltammogram does not

mean the non-existence of an

intermediate radical anion. The

intermediate may exist but

could have a lifetime that is too

short to allow its detection by

cyclic voltammetry.


5- 16

ET reactions not involving an ET intermediate (a radical anion, radical cation, or radical

depending on the starting material) follow a: dissociative electron transfer

mechanism. In this case the ET and bond cleavage are simultaneous.

Concerted vs stepwise ET mechanism

The mechanism of the initial ET step is very important. Consider the electron transfer

reaction below leading to the dissociation of the R-X chemical bond. This process is a

very common process to most organic compounds with a good leaving group such as

alkyl and aryl halides. The outcome of the generated radical greatly depend on whether

a radical anion is formed as an intermediate (outer sphere ET) or not (dissociative ET).

The radical can undergo a multitude of potential reactions as shown below.

RX + e- R + X

RX

?

R R-RRH

RNu

Nu(SRN1)

SH

e-

R

.-


5- 17

IV. Hush Marcus Theory vs the Dissociative ET Theory (Savéant’s Theory)

In electrochemical studies of organic compounds, a widely investigated process is the

Dissociative ET where a chemical bond is broken as a result of a first ET. When the one

electron-transfer product is an intermediate, the ET follows a stepwise mechanism and

can be described by the Hush –Marcus theory when the initial electron transfer step is

the rate determining step.1 On the other hand, when the ET and the bond breaking occur

in a concerted manner, Savéant2 proposed a model based on Morse curve picture of

bond breaking.

This model gives a similar quadratic activation-free energy relationship (eq 1), the

difference being the contribution of the bond dissociation energy (BDE) of the

fragmented bond to the activation barrier, ‡

0G , which involves only the solvent ( 0 ) and

the inner ( i ) reorganization energies for a stepwise mechanism (eq 2). ‡G (the

activation free energy), 0G (the reaction free energy) and ‡

s,0G and ‡

c,0G (i.e. the

activation energy at zero driving force) represent the intrinsic barriers for a stepwise and

a concerted ET respectively.

2

‡0

‡0

‡

41

G

GGG

o

(1)

4G and

4 G 0‡

c0,0‡

s0,XRi BDE

(2)

(1) See for example: (a) Marcus, R. A. Theory and Applications of Electron Transfers at Electrodes and

in Solution. In Special Topics in Electrochemistry; Rock, P. A., Ed.; Elsevier: New York, 1977; pp

161-179.

(2) Savéant, J-M. J. Am. Chem. Soc. 1987, 109, 6788. (b) Savéant, J-M. Dissociative Electron Transfer. In

Advances in Electron Transfer Chemistry; Mariano, P. S., Ed.; JAI Press: New York, 1994; Vol. 4, p.

53-116.

R-X + e

R-X

R + X

?


5- 18

How does the driving force affect the ET mechanism?

0

/ .RXRXE

0

/ . XRRXE

Potential Energy

Reaction Coordinate

RX + e-

RX + e-

Stepwise

Concerted

RX.-

R X+. -

-E

-E

Passage from a stepwise to a concerted mechanism upon decreasing the driving

force. Potential energy profiles. E: electrode potential.

How do know, in practice, whether one or the other mechanism is followed?

1- Experimental detection of the electron transfer intermediate (radical or radical ion):

a) High scan rate cyclic voltammetry: using ultra microelectrodes, scan rates as high

as a few million V/s may be reached, corresponding to lifetimes in the sub-s range.


5- 19

Example (increasing the scan rate in CV): reduction of 3,5-dinitrophenylthiocyanide

Cyclic Voltammetry in CH3CN/TBAF (0.1M) at a glassy carbon electrode, v = 0.2 V/s,

temperature = 20 oC of 3,5-dinitroPhSCN (3) 2 mM at v = 0.2 V/s (c) and v = 2 V/s (d).

b) Homogeneous catalysis allows the extension of the lifetime range up to the ns.

Homogeneous catalysis: consists of using a redox catalyst (P/Q) as an intermediate to

transfer electrons between the electrode and the substrate.

Homogeneous redox catalysis; (a) general process at electrode; (b) reaction sequence for a homogeneous dissociative electron transfer reduction.

SCN

O2N

O2N


5- 20

2- Transfer coefficient (), which is directly related to the intrinsic barrier (eq 3), is a

sensitive probe of the mechanistic nature of the first ET in dissociative processes:

‡0

0

0

‡

41

2

1

G G

GG (3)

The transfer coefficient can be determined from the electrochemical peak

characteristics (peak width, Ep-Ep/2), or from the slop of the Ep vs log(v) plot.

at 25o C

at 25o C

pE is the peak potential and 2/pE is the half peak potential

In a concerted mechanism, a value significantly lower than 0.5 is expected,

whereas an value close to or higher than 0.5 is expected in the case of a

stepwise mechanism.

11

)log(6.29

)log(2

v

Ep

v

Ep

F

RT

pppp EEEEF

RT

2/2/

15.47

85.1


5- 21

Photochemical initiation.

Photochemical irradiation is another efficient way to initiate ET reactions. Many

processes in nature are based on photoinduced ET. The most widely known one is of

course photosynthesis.

Under photochemical irradiation the ET can occur through a variety of mechanisms

(shown below): from irradiation of the donor (i) or of the acceptor (ii). A charge transfer

complex may also be formed: either before irradiation between ground state reactants,

or after irradiation between excited and ground state structures (iv). It is also possible to

generate solvated electrons, through irradiation of a sensitizer that is trapped by an

acceptor. Electron photo-ejection has been reported for anions such as phenolates and

thiolates as well as for neutral structures such as 4,4’-dimethoxystilbene. This latter

process is similar to pulse radiolysis.

Of the different techniques that have been developed to study photo-induced electron

transfer reactions the most widely used one is laser flash photolysis.

D

RX

D

D* + RX D + R + X

D*h

RX*h

D + RX*

D + RX (D,RX) h

RX + e-

D + e-h

(i)

(ii)

(iii)

(iv)

D + R + X

D + R + X

D + R + X

Different mechanisms for the photochemical initiation of a dissociative electron transfer.


5- 22

SUBSTITUENT' EFFETC ON ET INITIATED REACTIONS

a) Substituents' effect on the redox properties

b) Substituents's effect on the initial ET mechanism

c) Substituents effect on the kinetics

b) Substituents' effect on the product distribution

Products of the electrochemical reduction of substituted benzyl thiocyanates.

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