Quantum Mechanical Investigation of the Horner-Wadsworth-Emmons Reaction of Benzyl Pyridyl Ketone

摘要

The Horner-Wadsworth-Emmons (HWE) reaction is one of much versatile tools in syntheses of alpha,beta-unsaturated esters,alpha,beta-unsaturated ketones,and other conjugated systems.Mechanistically,it is generally accepted that the HWE reaction occurs with the addition of enolate derived from phosphonoacetate to aldehyde or ketone,followed by oxaphonphetane formation,pseudorotation,P-C bond cleavage,and then O-C bond cleavage.Stereochemically,the general phosphonoacetates with alkyl phosphonate sub-stituents give E-olefins,which can be explained as a result of the predominant formation of thermodynamically more stable threo adducts.According to an ab initio calculation performed by Ando,in the transition states of the nucleo-philic addition to the carbonyl group of acetaldehyde with the trimethyl phosphonoaceate enolate,a transition state leading to Z-olefin (erythro-TS-1) is more stable than threo-TS-1 due to a repulsive interaction between the phosphonate moiety and the methyl substituent of aldehyde in threo-TS-1 (Fig.1).