Magnesium-Catalyzed Mild Reduction of Tertiary and Secondary Amides to Amines

The first example of a catalytic hydroboration of amides for their deoxygenation to amines is reported. This transformation employs an earth-abundant magnesium-based catalyst. Tertiary and secondary amides are reduced to amines at room temperature in the presence of pinacolborane (HBpin) and catalytic amounts of To^MMgMe (To^M = tris­(4,4-dimethyl-2-oxazolinyl)­phenylborate). Catalyst initiation and speciation is complex in this system, as revealed by the effects of concentration and order of addition of the substrate and HBpin in the catalytic experiments. To^MMgH₂Bpin, formed from To^MMgMe and HBpin, is ruled out as a possible catalytically relevant species by its reaction with N,N-dimethylbenzamide, which gives Me₂NBpin and PhBpin through C–N and C–C bond cleavage pathways, respectively. In that reaction, the catalytic product benzyldimethylamine is formed in only low yield. Alternatively, the reaction of To^MMgMe and N,N-dimethylbenzamide slowly gives decomposition of To^MMgMe over 24 h, and this interaction is also ruled out as a catalytically relevant step. Together, these data suggest that catalytic activation of To^MMgMe requires both HBpin and amide, and To^MMgH₂Bpin is not a catalytic intermediate. With information on catalyst activation in hand, tertiary amides are selectively reduced to amines in good yield when catalytic amounts of To^MMgMe are added to a mixture of amide and excess HBpin. In addition, secondary amides are reduced in the presence of 10 mol % To^MMgMe and 4 equiv of HBpin. Functional groups such as cyano, nitro, and azo remain intact under the mild reaction conditions. In addition, kinetic experiments and competition experiments indicate that B–H addition to amide CO is fast, even faster than addition to ester CO, and requires participation of the catalyst, whereas the turnover-limiting step of the catalyst is deoxygenation.