Mannich-Type Reactions of Alkylzinc Reagents

Mannich-type reactions involving alkylzinc reagents have been developed using different strategies. We show that the addition of these organometallic species to sulfonyl imines occurs upon simple heating and affords Mannich products in moderate to excellent yields (14 examples, 30-99 %). Interestingly, N-alkyl imines were also found to be suitable partners after activation as an acyliminium by acetyl chloride (12 examples, 49-86 %) or, more originally, by TMSCl (14 examples, 26-87 %). These methods proved complementary, leading to the preparation of both N-protected secondary or tertiary amines and N-unprotected secondary amines in good yields, with an increased eco-compatibility, and under simple conditions.

Automated summary

Mannich-type reactions involving alkylzinc reagents have been developed using different strategies. We found that simple heating allows the addition of these organometallic species to sulfonyl imines, giving Mannich products in moderate to excellent yields (14 examples, 30-99%). Interestingly, N-alkyl imines can also be used as suitable partners after activation as an acyliminium by acetyl chloride (12 examples, 49-86%) or, more originally, by TMSCl (14 examples, 26-87%). These methods are complementary, providing both N-protected secondary or tertiary amines and N-unprotected secondary amines in good yields, with improved eco-compatibility and under simple conditions.