Diastereo- and enantioselective synthesis of 2,3- and 1,2-disubstituted 4-oxophosphonates via asymmetric Michael addition

Article abstract of DOI:10.1016/S0040-4020(97)00814-4

Asymmetric Michael addition of lithiated SAMP hydrazones (S)-2 to a variety of alkenylphosphonates (E)-3 followed by oxidative cleavage of the 1,4-adducts 4 afforded 2,3-disubstituted 4-oxophosphonates 5 with good to very good yields (58-80%), low to moderate diastereomeric (de = 6-74%) and excellent enantiomeric excesses (ee = >93%). Pure anti-diastereomers (ee = >93%) of 5 were obtained by separation of the stereoisomers by HPLC. In addition, the lithiated SAMP hydrazone (S)-2a was added to alkenylphosphonates (E)-3, and the lithio phosphonate anions were trapped with alkyl halides or sulfates, yielding 1,2-disubstituted 4-oxophosphonates 8 with moderate to good yields (38-69%), low to good diastereomeric (de = 10-77%) and high enantiomeric excesses (ee = >90%) after oxidative cleavage.