Rhodium-Catalyzed Asymmetric Hydrogenation Of Enamides

Chiral amines are important organic compounds and chemical intermediates, which widely exist in natural and non-natural products. They can be used as chiral auxiliaries, resolution reagents and drug synthons. With people's attaching importance to health and sustainable development, highly efficient, economical, environmentally friendly and green drug synthesis has become the major trend and goal. Transition metal catalyzed asymmetric hydrogenation is recognized as one of the most efficient, convenient and atom economic method for preparation of chiral amines. In spite that the remarkable achievements have been made in the field in the past 50 years, it is difficult to achieve the asymmetric hydrogenation of many special substrates. Therefore, the exploration of substrates with potential applications and their synthetic methods, and expansion of the application scope of the existing ligands are very significant for scientific research and practical application.Herein, three new kinds of substrates are designed and applied in Rhodium/chiral phosphine catalyzed asymmetric hydrogenation for the preparation of the corresponding chiral amine derivatives with high yields and selectivities under mild conditions. The research contents are as follows:1. We designed a new kind of tetra-substituted ?-acetoxyl ?-dehydroenamido esters which containing multiple functional groups. Chiral ?-hydroxyl-?-amino esters and their derivatives with high yields and enantioselectivities are successfully obtained via Rhodium/Duanphos catalytic asymmetric hydrogenation. Two chiral centers were constructed by one step (up to>99% con,97% ee).2. We have successfully developed the asymmetric hydrogenation of N-protected a-dehydroamino ketones catalyzed by Rhodium/DuanPhos under mild conditions. The highly efficient and selective hydrogenation of the alkenyl group can be achieved with the carbonyl group reserved. Alkyl substituted a-amino ketones are successfully obtained in high yields and excellent stereoselectivities (up to>99% con,>99% ee).3. The 4-substituted cyclic enamido esters were synthesized by two simple steps and firstly applied successfully in Rhodium catalyzed asymmetric hydrogenation to obtain the chiral 4-substituted oxazolinones with high yields and good stereoselectivities (up to>99% con,78% ee).