Catalytic Mannich-Type Reactions of Sulfonylimidates

A novel nucleophile, sulfonylimidate, has been successfully employed in Mannich-type reactions. Due to electron-withdrawing property of sulfonyl group Of sulfonylimidate, the acidity of alpha-proton is enhanced so that sulfonylimidate bearing no activating functional group at alpha-position is deprotonated by relatively weak base. DBU-catalyzed reactions of sulfonylimidates with protected imines in DMF provided the adducts in high yields with high anti selectivity. This reaction represents a wide substrate scope and a high catalytic turnover. A thorough kinetic Study revealed that rate-determining step is most likely deprotonation step in case of Ts-imidate. Alkali earth metal alkoxide and its HMDS salt also catalyze Mannich-type reactions of sulfonylimidates. The reactions catalyzed by Mg(O'Bu)(2) in DMF provided the adducts with high anti selectivity, while those catalyzed by [Sr(HMDS)(2)](2) gave syn selectivity. The asymmetric variant of Mannich-type reaction of sulfonylimidate was also achieved. Several transformations of sulfonylimidates to other functional groups were also demonstrated. Finally, direct-type catalytic formation of beta-amino acid ester from aldehyde and sulfonylimidate was achieved via in situ formation of sulfonylimine and DBU-assisted hydrolysis of sulfonylimidate.