A Mechanistic Study of the Horner-Wadsworth-Emmons Reaction: Computational Investigation on the Reaction Pass and the Stereochemistry in the Reaction of Lithium Enolate Derived from Trimethyl Phosphonoacetate with Acetaldehyde.
The mechanism of the Horner-Wadsworth-Emmons (HWE) reaction has been investigated using ab initio calculations (RHF/6-31+G). This study revealed that the HWE reaction of the lithium enolate derived from trimethyl phosphonoacetate with acetaldehyde occurs with the addition of the lithium enolate to aldehyde, followed by oxaphosphetane formation, pseudorotation, P-C bond cleavage, and then O-C bond cleavage. The oxaphosphetane formation is the rate-determining step both in the gas phase and in the presence of one dimethyl ether molecule. The transition state leading to trans-olefin is more stable than the transition state leading to cis-olefin. Product selectivity is reproduced by these calculations.
Ando
Kaori
K
College of Education, University of the Ryukyus, Nishihara-cho, Okinawa 903-0213, Japan.