Catalyst-free N1-regioselective aza-Michael addition of vinyl ketones with 1,2,3-triazole derivatives

Abstract

A catalyst-free N¹-regioselective aza-Michael reaction of vinyl ketones with 1,2,3-triazole derivatives has been efficiently developed. This method delivers the desired products with exceptional N¹-regioselectivity (N¹ : N² ratio >20 : 1) and in good isolated yields (up to 86%) and accommodates a diverse range of vinyl ketone derivatives, including acrolein, acrolein derivatives and amino acid derivatives. Mechanistic investigations show that the inherent nucleophilicity of the N¹ position in NH-triazoles and a water-involved six-membered ring transition state govern the N¹ selectivity. The protocol exhibits broad functional group tolerance across both coupling partners and requires no stringent reaction conditions, highlighting its operational simplicity.