Asymmetric Synthesis of 2-Alkyl-3-phosphonopropanoic Acids via P−C Bond Formation and Hydrogenation

Allylic acetates, formed by the acetylation of Baylis Hillman adducts, undergo addition of phosphorus nucleophiles to give stereoselectively
the Z-unsaturated esters. TFA cleavage of the tert-butyl ester and asymmetric hydrogenation of the unsaturated acid yields the phosphono
alkyl propanoic acid moiety, commonly found in phosphonate- and phosphinate-based enzyme inhibitors.

由贝利斯-希尔曼（Baylis Hillman）加成物经乙酰化反应生成的烯丙基乙酸酯（allylic acetates），可与磷亲核试剂发生加成反应，立体选择性地得到Z型不饱和酯。经三氟乙酸（TFA）裂解叔丁基酯，并对所得不饱和酸进行不对称氢化后，即可得到膦酰基烷基丙酸结构单元，该结构单元常见于基于膦酸酯与次膦酸酯的酶抑制剂中。