Controlled and chemoselective reduction of secondary amides.
This communication describes a metal-free methodology involving an efficient and controlled reduction of secondary amides to imines, aldehydes, and amines in good to excellent yields under ambient pressure and temperature. The process includes a chemoselective activation of a secondary amide with triflic anhydride in the presence of 2-fluoropyridine. The electrophilic activated amide can then be reduced to the corresponding iminium using triethylsilane, a cheap, rather inert, and commercially available reagent. Imines can be isolated after a basic workup or readily transformed to the aldehydes following an acidic workup. The amine moiety can be accessed via a sequential reductive amination by the addition of silane and Hantzsch ester hydride in a one-pot reaction. Moreover, this reduction tolerates various functional groups that are usually reactive under reductive conditions and is very selective to secondary amides.
Pelletier
Guillaume
G
Department of Chemistry, Université de Montréal, P.O. Box 6128, Station Downtown, Montréal, Québec, Canada H3C 3J7.
Bechara
William S
WS
Charette
André B
AB
D000447:Aldehydes / Q000737:chemistry; D000577:Amides / Q000737:chemistry*; D000588:Amines / Q000737:chemistry; D007097:Imines / Q000737:chemistry; D010084:Oxidation-Reduction; D013379:Substrate Specificity
D000447:Aldehydes; D000577:Amides; D000588:Amines; D007097:Imines