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.