Highly chemoselective reduction of amides (primary, secondary, tertiary) to alcohols using SmI₂/amine/H₂O under mild conditions

Highly chemoselective direct reduction of primary, secondary, and tertiary amides to alcohols using SmI₂/amine/H₂O is reported. The reaction proceeds with C-N bond cleavage in the carbinolamine intermediate, shows excellent functional group tolerance, and delivers the alcohol products in very high yields. The expected C-O cleavage products are not formed under the reaction conditions. The observed reactivity is opposite to the electrophilicity of polar carbonyl groups resulting from the n_X → π_C=O (X = O, N) conjugation. Mechanistic studies suggest that coordination of Sm to the carbonyl and then to Lewis basic nitrogen in the tetrahedral intermediate facilitate electron transfer and control the selectivity of the C-N/C-O cleavage. Notably, the method provides direct access to acyl-type radicals from unactivated amides under mild electron transfer conditions.