Sulfonyl as a Traceless Activation Group for Enantioselective Mannich Reaction Catalyzed by Thiourea to Access Chiral β-Aminophosphonates

An efficient enantioselective Mannich reaction of N-protected α-sulfones with β-benzenesulfonyl phosphonates was developed by using a chiral cinchona alkaloid-derived thiourea as a catalyst. This method was used to obtain a series of chiral α-sulfonyl-β-aminophosphonates in yields of up to 96% with 89:11 dr and 88% ee. These compounds were further transformed into β-aminophosphonates or chiral azetidines with various functional groups by a Horner–Wadsworth–Emmons/aza-Michael addition reaction sequence.