A highly enantioselective, Pd-TangPhos-catalyzed hydrogenation of N-tosylimines.

Although significant progress has been made in the catalytic asymmetric reduction of ketones and olefins over the last few decades, the asymmetric reduction of imines remains a major challenge. Enantioselective reductive amination with organocatalysts has recently been reported, and a number of transition-metal-based catalysts, such as those containing Rh, Ru, Ti, Zr, and Ir, have been applied to the asymmetric hydrogenation of imines. However, this method has been less successful than the hydrogenation of other substrates. The main obstacles in solving the problems in this hydrogenation approach include different enantioselectivities for E and Z isomers of acyclic imines, the instability of some imines prepared from ketones, and the inhibitory effect of the amine products on the metal catalysts. In order to solve these problems, N-tosylimines were selected as the hydrogenation substrates since they are relatively stable and can be easily obtained from the corresponding ketones exclusively as the E isomer. In addition, the strongly electron-withdrawing character of the tosyl group reduces the inhibitory effect of the reduction product on the catalysts, which might lead to higher reactivity. These advantages of N-tosylimines as substrates prompted us to look for a good reduction catalyst for the substrates. To the best of our knowledge, the asymmetric hydrogenation of N-tosylimines has rarely been explored, and the best result reported so far is the 84% ee reported by the Charette group using a Ru–Binap catalyst. In our search for effective hydrogenation catalysts for the reduction of N-tosylimines, we have explored this trans-