Amino Sulfonamide Catalyst for the Direct Mannich Reaction of N-Boc Imines

Significance

The Maruoka group found that their previously introduced axially chiral amino sulfon­amide 1 (J. Am. Chem. Soc. 2005, 127, 16408) is a suitable catalyst for the direct Mannich reaction between aldehydes and N-Boc-protected imines. The catalyst was systematically designed to bear a strongly acidic sulfonamide for the activation of the electrophile and a less nucleophilic amine moiety for the formation of less nucleophilic enamines to suppress side reactions such as aldehyde self-aldol reactions. With this catalyst, the Mannich reaction between acetaldehyde and N-Boc-protected imines proceeded with good yields (up to 92%) and outstanding enantioselectivities (er ÷ 99:1). Other aldehydes gave the corresponding anti-Mannich products (dr up to > 20:1) in good yields (up to 93%) and perfect enantioselectivities (er ÷ 99:1) as well.