1I-K. Pericyclic ReactionsI. Basic PrinciplesNicolaou, K. C. et al. J. Am. Chem. Soc. 1982, 104, 5560. (Endiandric acids)Categories of Pericyclic Reactions• among the reactants and products usually at least one moleculeis unsaturated• the reactions involve the formation or scission of σ-bonds andthe consumption or generation of π-bonds• the electronic reorganization occurs in some sort of cyclic arrayof the participating atomic centers.Dr. P. WipfChem 23202/20/20072Pericyclic 6-el. Processes:Pericyclic reactions are apparently concerted: the electronic rearrangements involved inbond-making/bond-breaking proceed simultaneously in a one-step (one TS‡) process.Dr. P. WipfChem 23202/20/20073Woodward-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,and it is more intuitive that the original orbital symmetryarguments.- 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 allorbitals involved during the transformation of reactants intoproducts, the frontier orbital approach makes predictions for theoutcome of pericyclic reactions based on the highest occupiedmolecular orbital (HOMO) and the lowest unoccupied molecularorbital (LUMO). In this, the electrons in the HOMO of one reactantare looked upon as analogous to the outer (valence) electrons ofan atom, and reaction is then envisaged as involving the overlap ofthis (HOMO) orbital with the LUMO of the other reactant. Where,as in electrocyclic reactions, only one species is involved only theHOMO needs be considered.Dr. P. WipfChem 23202/20/20074If, 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:Dr. P. WipfChem 23202/20/200752. The Dewar-Zimmerman Theory of AromaticTransition States.This analysis is possibly the most general and easiest to apply to a broad range ofpericyclic reactions, but it is also the least anchored in fundamental physicalprinciples.For applying this model, choose a basis set of 2p atomic orbitals for all atomsinvolved (1s for hydrogens).After assigning any phases to these orbitals (no relationship to MO’s is required!),connect the orbitals that interact in the starting materials, before the reactionbegins. Allow the reaction to proceed according to the postulated geometry;connect the lobes that begin to interact and were not connected in the startingmaterials.Count the number of phase inversions that occur - a phase inversion within anorbital is not counted.Based on the number of phase inversion of the orbital perimeter, identify thetopology of the system:Odd # of phase inversions: Möbius topologyEven # of phase inversions: Hückel topologyThe 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 thermally allowed.If the transition state is antiaromatic, a photochemical process isrequired.Dr. P. WipfChem 23202/20/200763. The Woodward-Hoffmann Theory. This was the firsttheory to explain and predict the outcome of many pericyclicreactions. Therefore, it brought order and understanding tomany thermal and photochemical reactions. However, itused correlation diagrams, which are difficult and time-consuming to 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.Dr. P. WipfChem 23202/20/20077Dr. P. WipfChem 23202/20/20078- [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(Stevens rearrangement):- [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):Dr. P. WipfChem 23202/20/20079CopeRearrangementsThermal 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.Dr. P. WipfChem 23202/20/200710Dr. P. WipfChem 23202/20/200711Dr. P. WipfChem 23202/20/200712- 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.Claisen Rearrangements- Wipf, P. In ComprehensiveOrganic Synthesis; B. M. Trost, I.Fleming and L. A. Paquette, Ed.;Pergamon: Oxford, 1991; Vol. 5; pp827-874.Dr. P. WipfChem 23202/20/200713The
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