1 IIE. Pericyclic Reactions Boger Notes: p. 213 - 354 (Chapter X) Carey/Sundberg: B p. 331-432 (Chapter B 6) II. Special Topics Categories of Pericyclic Reactions - among the reactants and products usually at least one molecule is unsaturated - the reactions involve the formation or scission of sigma-bonds and the consumption or generation of pi-bonds - the electronic reorganization occurs in some sort of cyclic array of the participating atomic centers. Pericyclic 6-el. Processes: Dr. P. Wipf 1 4/18/2006
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IIE. Pericyclic Reactions
Boger Notes: p. 213 - 354 (Chapter X)Carey/Sundberg: B p. 331-432 (Chapter B 6)
II. Special Topics
Categories of Pericyclic Reactions
- among the reactants and products usually at least one molecule is unsaturated
- the reactions involve the formation or scission of sigma-bonds and the consumption or generation of pi-bonds
- the electronic reorganization occurs in some sort of cyclic array of the participating atomic centers.
Pericyclic 6-el. Processes:
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Pericyclic reactions are apparently concerted: the electronic rearrangements involved inbond-making/bond-breaking proceed simultaneously in a one-step (one TS‡) process.
Spontaneus Conrotatory 4π and 8π Electrocyclic Reactions
- Paquette, L. A.; Doyon, J. J. Org. Chem. 1997, 62, 1723. Monoprotonation of 1and 2 at the less substituted site leads to a single polyquinane product.
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- [2,3] Sigmatropic rearrangement of sulfoniumylids:
- [1,2] Sigmatropic rearrangement of sulfoniumylids:
- [2,3] Sigmatropic rearrangement of allylic sulfoxides to allyl sulfenates (Mislow-Evansrearrangement):
- Wipf, P.; Lim, S. Chimia 1996, 50,157.
- [1,2] Sigmatropic rearrangement of quaternary ammonium salts to tertiary amines (Stevensrearrangement):
- [2,3] Sigmatropic rearrangement of quaternary benzylic ammonium salts to tertiary amines (Sommelet-Hauser rearrangement):
- [1,2] Sigmatropic rearrangement of tertiary amine oxides to substituted hydroxylamines (Meisenheimerrearrangement):
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CopeRearrangements
Thermal rearrangement of 1,5-dienes to isomeric 1,5-dienes:
Specific value for modern organic synthesis:
- Parent Cope involves no requirement for acid or base catalysis and can thus accommodate a widevariety of functional groups.- One of the most powerful methods of synthesis of medium rings.- Due to the highly ordered cyclic TS, the reaction is extremely stereospecific. Two unsymmetrical doublebonds and two asymmetric centers are translated to four new elements of stereochemistry, usually withnear quantitative symmetric transmission.The development of the oxy-Cope and anionic oxy-Cope reactions has greatly extended the utility of theCope rearrangement by allowing easier access to diene substrates, lowering the temperature required forrearrangement, and producing carbonyl substrates irreversibly.
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- Davies, H. M. L.; Calvo, R.; Ahmed, G. Tetrahedron Lett. 1997, 38, 1737. Type II(Roush, W. R. In Comprehensive Organic Synthesis; B. M. Trost and I. Fleming, Eds.;Pergamon Press: Oxford, 1991; Vol. 5; pp 513) cycloannulations betweenvinylcarbenoids and furans result in the rapid construction of fused [4.3.1.]-bicyclicsystems.
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- Corey, E. J.; Kania, R. S. Tetrahedron Lett. 1998, 39, 741. Dianion accelerated oxy-Coperearrangement can produce strained medium ring compounds.
Claisen Rearrangements
- Wipf, P. In ComprehensiveOrganic Synthesis; B. M. Trost, I.Fleming and L. A. Paquette, Ed.;Pergamon: Oxford, 1991; Vol. 5; pp827-874.
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The Aromatic ClaisenRearrangement
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The Ireland Silyl Ester Enolate Rearrangement
Several factors contribute to the versatility of the ester enolate Claisenrearrangement.Among these are the ability to use a stoichiometric combination of the alcohol andthe acid components, the relatively low temperature of the pericyclic process thatallows for the assembly of complex, highly functionalized structures, and thetransformation of a carbon-oxygen into a carbon-carbon bond that lends itself easilyto the assembly of contiguous quaternary centers.
Another particularly important aspect of the Ireland rearrangement is that, throughan efficient control of ketene acetal geometry, a highly reliable and predictabletransfer of stereochemistry from starting material to product can be realizedDeprotonation of crotyl ester with LDA in THF leads, via the selective formation ofthe kinetically favored (Z)-ester enolate, upon silylation to the (E)-silyl ketene acetal.After rearrangement at 65°C and mild hydrolysis of the silyl ester, a 87 : 13 ratio ofg,d-unsaturated acids is isolated in 79% yield. These two products can be obtainedin a 19 : 81 ratio by using 23%HMPA/THF as a solvent system for the generation ofthe thermodynamically favored (Z)-silyl ketene acetal via the corresponding (E)-lithium enolate. Wipf, P., "Claisen rearrangements." In B. M. Trost, I. Fleming and L. A. Paquette, editors.Comprehensive organic synthesis. Vol 5. Oxford: Pergamon; 1991. p. 827-874.
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Ireland, R. E.; Wipf, P.; Xiang, J.-N. J. Org. Chem. 1991, 56, 3572:
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- R. E. Ireland and M. D. Varney, J. Org. Chem., 1986,51, 635.
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Woodward-Hoffmann RulesAmong the theories that are commonly used to analyze pericyclicreactions, three are generally considered to be the most useful:
1. Fukui’s Frontier MO interactions. This analysis applies HOMO-LUMO interactions as well as orbitals close to HOMO & LUMO, andit is more intuitive that the original orbital symmetry arguments.
- Coulson, C. A.; Longuet-Higgins, H. C. Proc. Roy. Soc.A 1947, 192, 16.- Klopman & Salem (JACS 1968, 90, 223, 543, 553).- Fukui, K. Acc. Chem. Res. 1971, 4, 57.
Rather than considering the relative phases, i.e. symmetry, of all orbitalsinvolved during the transformation of reactants into products, the frontierorbital approach makes predictions for the outcome of pericyclic reactionsbased on the highest occupied molecular orbital (HOMO) and the lowestunoccupied molecular orbital (LUMO). In this, the electrons in the HOMO ofone reactant are looked upon as analogous to the outer (valence) electronsof an atom, and reaction is then envisaged as involving the overlap of this(HOMO) orbital with the LUMO of the other reactant. Where, as inelectrocyclic reactions, only one species is involved only the HOMO needsbe considered.
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If, upon examination of the interactions that occur in the frontierorbitals (HOMO, LUMO if applicable, otherwise only HOMO) theinteractions are constructive (of the same phase, the reaction isconsidered “allowed”.If the orbital overlap is destructive (i.e. of different phase), then thereaction is “forbidden”.
Berson, J. A.; Nelson, G. L. J. Am.Chem. Soc. 1967, 89, 5303:
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2. The Dewar-Zimmerman Theory of Aromatic Transition States.This analysis is possibly the most general and easiest to apply to abroad range of pericyclic reactions, but it is also the least anchored infundamental physical principles.
For applying this model, choose a basis set of 2p atomic orbitals forall atoms involved (1s for hydrogens).After assigning any phases to these orbitals (no relationship to MO’sis required!), connect the orbitals that interact in the startingmaterials, before the reaction begins. Allow the reaction to proceedaccording to the postulated geometry; connect the lobes that begin tointeract and were not connected in the starting materials.Count the number of phase inversions that occur - a phase inversionwithin an orbital is not counted.Based on the number of phase inversion of the orbital perimeter,identify the topology of the system:Odd # of phase inversions: Möbius topologyEven # of phase inversions: Hückel topology
The transition state can now be assigned as antiaromatic or aromatic,based on the number of electrons in the system:Möbius topology: Aromatic for 4n, Antiaromatic for 4n+2Hückel topology: Aromatic for 4n+2, Antiaromatic for 4nif the transition state is aromatic, then the reaction is thermallyallowed. If the transition state is antiaromatic, a photochemicalprocess is required.
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3. The Woodward-Hoffmann Theory. This was the first theoryto explain and predict the outcome of many pericyclicreactions. Therefore, it brought order and understanding tomany thermal and photochemical reactions. However, it usedcorrelation diagrams, which are difficult and time-consumingto apply.
For thermally allowed reactions, the occupied orbitals of thestarting materials must correlate with occupied orbitals of theproduct. Correlation of orbitals is determined in terms ofsymmetry relationships.
Dolbier, W. R., Jr.; Koroniak, H.; Houk, K. N.; Sheu, C. "Electronic control ofstereoselectivities of electrocyclic reactions of cyclobutenes: A triumph of theory in theprediction of organic reactions." Accounts of Chemical Research 1996, 29, 471-477.
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Woodward-Hoffman Rules
For the reaction indicated below, please answer the following questions.I. How many π electrons are involved in the transformation?II. Is this reaction an example of an electrocyclic process, a cycloaddition reaction ora sigmatropic rearrangement? Where appropriate assign an [m,n] designation to thereaction.III. Is this reaction conrotary or disrotary? (when applicable)IV. Is this reaction suprafacial or antarafacial? (when applicable)V. Apply (a) the FMO formalism (b) the D-Z model, and (c) a correlation diagram inthe analysis of the stereoelectronic control of this reaction.VI. Is this reaction allowed or forbidden under thermal control?
P1
Woodward-Hoffman Rules
For the reaction indicated below, please answer the following questions.I. How many π electrons are involved in the transformation?II. Is this reaction an example of an electrocyclic process, a cycloaddition reaction ora sigmatropic rearrangement? Where appropriate assign an [m,n] designation to thereaction.III. Is this reaction conrotary or disrotary? (when applicable)IV. Is this reaction suprafacial or antarafacial? (when applicable)V. Apply (a) the FMO formalism (b) the D-Z model, and (c) a correlation diagram inthe analysis of the stereoelectronic control of this reaction.VI. Is this reaction allowed or forbidden under thermal control?
P2
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Woodward-Hoffman Rules
For the reaction indicated below, please answer the following questions.I. How many π electrons are involved in the transformation?II. Is this reaction an example of an electrocyclic process, a cycloaddition reaction ora sigmatropic rearrangement? Where appropriate assign an [m,n] designation to thereaction.III. Is this reaction conrotary or disrotary? (when applicable)IV. Is this reaction suprafacial or antarafacial? (when applicable)V. Apply (a) the FMO formalism (b) the D-Z model, and (c) a correlation diagram inthe analysis of the stereoelectronic control of this reaction.VI. Is this reaction allowed or forbidden under thermal control?
