Hydroxy Group Directed Catalytic Hydrosilylation of Amides

Abstract

Chemo-and site-selective hydrosilylation of αor β-hydroxy amides using organocatalyst B(C 6 F 5 ) 3 and commercially available hydrosilanes is described. This transformation is operative under mild conditions and tolerates a wide range of functional groups. The reaction was applied for selective reduction of a specific amide group of the therapeutically important cyclic peptide cyclosporin A, demonstrating the potential usefulness of this catalytic method in late-stage structural transformations of drug lead molecules.

Deoxygenation of Primary Amides to Amines with Pinacolborane Catalyzed by Ca[N(SiMe3)2]2(THF)2

“…Nevertheless, this procedure not only raises significant safety concerns and environmental issues but also suffers from the lack of selectivity in the presence of various functional groups. As amide hydrogenations are widely processed along with elevated pressure and temperature at the cost of expensive metal catalysts, a catalytic hydrogenation strategy should be well-received for its atom economy (Scheme b). , Recent progress shows that catalytic hydrosilylation is a promising method for transforming amides to amines; however, it requires an excessive amount of expensive and air-sensitive silanes (Scheme c). − It is, therefore, necessary and meaningful to develop new methodology to address the challenges in amide reduction.…”

Defunctionalisation catalysed by boron Lewis acids

“…In 2018, Sohma, Kanai, and co-workers described a B(C 6 F 5 ) 3catalysed chemo-and regioselective reduction of various hydroxy amides 17i-k with MePhSiH 2 as the reductant to synthesize 1,n-aminoalcohols under mild conditions with high functional group tolerance (Scheme 17). 43 This process undergoes a sequence of B(C 6 F 5 ) 3 -catalysed dehydrogenative silylation of the hydroxy group and selective deoxygenation through intramolecular Lewis acid/base type interaction between the silicon atom and oxygen atom of the amide carbonyl group. The application of this catalytic system to chemo-and site-selective reduction of a specic amide bond in cyclosporin A, which contains four secondary and seven tertiary amide bonds, demonstrated the power of this catalytic system when applied to complex molecules.…”

Homoleptic Bis(trimethylsilyl)amides of Yttrium Complexes Catalyzed Hydroboration Reduction of Amides to Amines

“…Xu and coworkers found HCO 2 H/NEt 3 and ammonia borane are alternative hydrogen sources for transfer hydrogenation of amides to corresponding amines (Scheme b) . Catalytic hydrosilylation of amides has been extensively explored without high-pressure equipment and high temperature, with amides converted into the amines by noble metals, earth-abundant metals, simple bases, and metal-free conditions (Scheme c) . The elegant work of Beller, Brookhart, and Adolfsson involving the metal-catalyzed (such as Fe, Ir, and Mo) hydrosilylation of amides allows facile access to amines.…”