A Practical Procedure for Reduction of Primary, Secondary and Tertiary Amides to Amines

Abstract

A mild and general procedure for reduction of primary, secondary, and tertiary amides using catalytic triruthenium dodecacarbonyl and 1,1,3,3-tetramethyldisiloxane as reductant is described. The reaction is tolerant of numerous functional groups, and the amine products can often be isolated by direct crystallization as hydrochloride salts. The catalyst and silane are commercially available, air stable, and inexpensive, making the procedure accessible for both laboratory and large-scale applications.

Amide Activation in Ground and Excited States

“…An unprecedented number of examples can be found in the literature to reduce amides to substituted amines, using numerous reduction agents (most generally metal hydrides). The situation is illustrated by a few selected citations [ 31 , 69 , 92 , 93 , 94 , 95 , 96 , 97 ]. Strong reduction agents are a common feature of these methods, since generally amides are very resistant against reduction.…”

Selective Reduction of Amides to Amines by Boronic Acid Catalyzed Hydrosilylation

“…Notable recent examples of chemoselective reductions have been performed even in the presence of inexpensive Fe11 or Zn salts 12. Nevertheless, despite the progress made none of the known catalytic hydrosilylation methods can directly reduce all types of amide bonds (tertiary, secondary, and primary) in the presence of other functional groups such as ester, nitro, and nitrile groups 13…”

Amine synthesis via transition metal homogeneous catalysed hydrosilylation

“…of TMDS. 69 In 2013, we reported an unexpected selective ruthenium(II)catalysed hydrosilylation of primary amides leading to symmetric secondary amines. 70 This reaction was performed with 1-2 mol% of [RuCl 2 (mestylene)] 2 C30, 3 equiv.…”