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.
School of Chemistry, University of Manchester , Oxford Road, Manchester M13 9PL, United Kingdom.
Michal
M
Szostak
Malcolm
M
Spain
Andrew J
AJ
Eberhart
David J
DJ
Procter
D000438:Alcohols / Q000737:chemistry*; D000577:Amides / Q000737:chemistry*; D000588:Amines / Q000737:chemistry*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D012493:Samarium / Q000737:chemistry*; D013237:Stereoisomerism; D014867:Water / Q000737:chemistry*
D000438:Alcohols; D000577:Amides; D000588:Amines; D014867:Water; D012493:Samarium