A Powerful Brønsted Acid Catalyst for the Organocatalytic Asymmetric Transfer Hydrogenation of Imines

Abstract

The catalytic hydrogenation of alkenes, ketones, and imines is arguably one of the most important transformations in chemistry. Powerful asymmetric versions have been realized that require metal catalysts or the use of a stoichiometric amount of metal hydrides [Eq. (1)]. [1] Although effective and industrially relevant catalytic asymmetric hydrogenations and transfer hydrogenations of olefins and ketones have been developed, the corresponding imine reductions, although potentially highly useful for the synthesis of enantiomerically pure amines, are less advanced.[2] Living organisms employ organic dihydropyridine cofactors such as nicotinamide adenine dinucleotide (NADH) in combination with enzyme catalysts for the reduction of imines.[3] Chemical transition metal catalyzed asymmetric imine reductions have also been developed, [4] and are used, in at least one case, on an industrial scale. [5] However, with the exception of interesting Lewis base catalyzed asymmetric imine hydrosilylations, [6] organocatalytic and metal-free variants were not known. Recently, we and MacMillan and co-workers developed an asymmetric transfer hydrogenation of a,b-unsaturated aldehydes catalyzed by a chiral ammonium salt by using Hantzsch esters as a biomimetic hydrogen source. [7] Rueping et al. [8] very recently reported the development of a novel and elegant approach using Hantzsch esters as the reducing reagent for the catalytic asymmetric reduction of imines using a chiral Brønsted acid catalyst previously developed by Akiyama et al.

Hydrosilylation of Ketone and Imine over Poly‐N‐Heterocyclic Carbene Particles

“…Almost all asymmetric hydrosilylation reactions were catalyzed by chiral catalysts. [6] A chiral silane was very rarely used due to the difficulty in its preparation.…”

“…[5] Although hydrogenation is widely practiced industrially, it faces shortcomings such as, metal leaching, high-pressure requirements, expensive catalysts, and difficulty in catalyst recycling. [6] Developing effective metal-free organocatalysts for the hydrosilylation of ketones and imines has attracted great interest. [7] In comparison, a robust and simple heterogeneous organocatalyst for ketone hydrosilylation would be even more desirable since it could be both environmentally friendly and more economical.…”

Single Nucleotide‐Catalyzed Biomimetic Reductive Amination

“…[12][13][14][15][16][17] Recently some fascinating reports on asymmetric imine reduction using substituted chiral binaphthyl hydrogen phosphate as catalyst were reported by List (5h), [18] and Rueping (5g). [19] Extensive [20] and Kočovský [21] using trichlorosilane and a Lewis base organocatalyst.…”

Development of Chiral Thiourea Catalysts and Its Application to Asymmetric Catalytic Reactions

“…Recently, hydrogen-bond donors such as ureas/thioureas, [10][11][12][13][14][15][16][17][18][19][20][21][22][23] BINOL/diols, [24][25][26][27][28][29][30][31][32] and phosphoric acids [33][34][35][36][37][38][39][40] have been also recognized as efficient organocatalysts. Novel urea and thiourea derivatives were developed as organocatalysts and their potential as a general acid has been successfully demonstrated by several groups.…”