Hydrogenolysis is an important synthetic method in organic chemistry, and has been widely applied in industrial processes, natural product synthesis, and the removal of waste materials. In practice, most hydrogenolysis reactions have been used for the synthesis of racemic or achiral compounds. Very few studies on asymmetric homogeneous hydrogenolysis have been reported. The first example, reported by Chan and Coleman, was a homogeneous asymmetric hydrogenolysis of sodium epoxysuccinate through desymmetrization with chiral rhodium catalysts with moderate enantioselectivity. Subsequently, a water-soluble sulfonated-phosphine–rhodium catalyst system for the asymmetric hydrogenolysis of epoxides was described by Bakos et al. , but the products were obtained with only 39% ee. K ndig and co-workers documented a desymmetrization ofmeso dihalide complexes by asymmetric hydrogenolysis, which led to planar chiral organometallic complexes. Very recently, asymmetric hydrogenolysis of racemic tertiary alcohols was also successfully developed. Despite considerable efforts, these reactions are far from ideal because of low optical enrichment of the hydrogenolysis product and a relatively limited range of substrates. Therefore, the search for an efficient strategy for homogeneous asymmetric hydrogenolysis and extension of the scope of such processes to a wider range of substrates is still of great significance. Palladium has been extensively investigated as a heterogeneous hydrogenolysis catalyst. In contrast, palladiumcatalyzed homogeneous asymmetric hydrogenolysis is still rare. Recently, homogeneous palladium catalysts were successfully utilized for the asymmetric hydrogenation of ketones, imines, heteroaromatic compounds, and enesulfonamides by us and other research groups. Considering the straightforward synthesis of N-sulfonyl aminoalcohols from commercially available starting materials and the usefulness of the hydrogenolysis products, chiral amines with two contiguous stereogenic centers, we speculated that a chiral palladium catalyst system could be applied for the homogeneous asymmetric hydrogenolysis of N-sulfonyl aminoalcohols (Scheme 1). Herein, we report the palladiumcatalyzed formal asymmetric hydrogenolysis of N-sulfonyl aminoalcohols to give chiral amines with two contiguous stereocenters with up to 94% ee. Furthermore, both “dynamic kinetic asymmetric transformation” and “dynamic kinetic resolution” phenomena were observed. Prior to our study, we wanted to synthesize the chiral N((1R,2S)-1-butyl-2,3-dihydro-1H-inden-2-yl)-4-methylbenzenesulfonamide 2a by hydrogenolysis of the benzylic hydroxy group of theN-sulfonyl aminoalcohol (1S,2S)-1a with Pd/C as the catalyst in the presence of trifluoroacetic acid (TFA). Surprisingly, although the reaction proceeded smoothly [Eq. (1)], the stereogenic center of the C N bond was also racemized: only racemic cis-2a was obtained in 76% yield. This observation suggested that an achiral intermediate might be involved in this process, and that the asymmetric hydrogenolysis of racemic N-sulfonyl aminoalcohols might be possible. In this context, we began to study the homogeneous palladium-catalyzed asymmetric hydrogenolysis of racemic N-sulfonyl aminoalcohols.
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Feb 1, 2016
Dylan Dagoneau + 3
Open Access