Transition metal-catalyzed asymmetric hydrogenation for synthesis of chiral amines

Synthesis of chiral amine is one of the major tasks in organic chemistry since chiral amines play important roles in pharmaceutical and agrochemical industry. Among those various methods for chiral amine synthesis, transition metal-catalyzed asymmetric hydrogenation is one of the most efficient asymmetric catalytic technology both on the laboratory and the production scale in synthetic organic chemistry due to its high efficiency and atom economy. In this dissertation, the asymmetric hydrogenation of two types of cyclic imines, direct asymmetric reductive amination and the asymmetric hydrogenation of pyridines were explored for makingof chiral amines. The asymmetric reduction of cyclic imines and N-hereromatic compounds remains a challenge in modern synthesis due to the inhibitory effect from the amine product and the coordination difficulty of the imine substrates to the transition metal center. Our Ir–f-Binaphane catalytic system was proved to be efficient for two types of cyclic imine substrates, 2-arylpyrrolines and dihydroisoquinoline. A ‘green’ method, the direct reductive amination of simple ketones was explored using phenylhydrazide as the nitrogen source. With help of several additives, excellent reactivity (up to 1000 TONs) and enantioselectivities (up to 99% ee) were achieved in iridium–f-Binaphane catalyzed reaction. The direct hydrogenation of pyridines is hard to achieve. The strategy we used is to dearomatize the pyridine ring by addition of an easy-removal protecting group, benzyl, on the nitrogen of pyridines. Collaborating with Merck Catalysis group, and using the neutral iridium–MP2-SegPhos catalytic system, various N-benzyl-2-arylpyridines were hydrogenated under mild condition and high enantioselectivities were achieved.Ph. D.Includes bibliographical referencesby Mingxin Chan