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

Abstract

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 H PLC. 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.