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

采用从头计算方法研究了Horner-Wadsworth-Emmons（HWE）反应的机理。该研究表明，衍生自三甲基膦酰基乙酸酯的烯醇化锂与乙醛的HWE反应发生在烯醇化锂加成到醛（TS 1）上，随后形成氧杂磷杂环己烷（TS 2），假膦酰基化，P-C键断裂，然后O-C键断裂。氧杂磷杂环己烷的形成（TS 2）是在气相中和在一个或两个二甲醚分子的存在下的速率决定步骤。在TS 2中，导致反式烯烃的过渡态比导致顺式烯烃的过渡态更稳定。通过这些计算再现产物选择性。研究了二苯膦酰基乙酸甲酯衍生的烯醇化锂与乙醛在一个二甲醚分子存在下的反应。虽然该反应发生类似，但在自洽反应场（SCRF）方法中，速率决定步骤是与醛（TS 1）加成。在TS 1中，导致顺式烯烃的过渡态比导致反式烯烃的过渡态更稳定。这些计算表明，反式烯烃可以在非极性溶剂中在较高温度下制备，另一方面，顺式烯烃可以通过使用二苯基膦酰基乙酸甲酯在极性溶剂中在低温下制备。

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.