A Mechanistic Study of the Horner-Wadsworth-Emmons Reaction by ab initio Calculations

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The mechanism of the Horner-Wadsworth-Emmons (HWE) reaction has been investigated using ab initio calculations. 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 (TS1), followed by oxaphosphetane formation (TS2), pseudoratation, P-C bond cleavage, and then O-C bond cleavage. The oxaphosphetane formation (TS2) is the rate-determining step both in the gas phase and in the presence of one or two dimethyl ether molecules. In TS2, 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. Also the reaction of the lithium enolate derived from methyl diphenylphosphonoacetate with acetaldehyde was studied in the presence of one diemthyl ether molecule. Although this reaction occurs similary, the rate-determining step is the addition to aldehyde (TS1) in a Self-Consistent Reaction Field (SCRF) method. In TS1, the transition state leading to cis-olefin is more stable than the transition state leading to trans-olefin. These calculations show that trans-olefins can be made in a non-polar solvent at a higher temperature, on the other hand, cis-olefins can be made by using methyl diphenylphosphonoacetate in a polar solvent at a low temperature.