Abstract
Chiral amines are one of the ubiquitous functional groups in fine chemical, pharmaceutical and agrochemical products, and the most convenient, economical, and eco-benign synthetic pathway to these amines is direct asymmetric reductive amination (DARA) of prochiral ketones. This paper shows that a wide range of aliphatic ketones can be directly aminated under hydrogenation conditions, affording chiral amines with good to excellent yields and with enantioselectivities up to 96% ee. The catalysis is effected by the cooperative action of a cationic Cp*Ir(III) complex and its phosphate counteranion.
Highlights
The use of enantiomerically pure compounds has steadily increased in the pharmaceutical and agrochemical industry in the past decades
We started with optimization of the direct asymmetric reductive amination (DARA) conditions by considering the model reaction of
Aiming to boost the conversion and ee, we studied the effect of extra acid 3 and molecular sieves on the DARA
Summary
The use of enantiomerically pure compounds has steadily increased in the pharmaceutical and agrochemical industry in the past decades. Wills and co-workers reported an intramolecular reductive amination under transfer hydrogenation conditions with a Ru(II)TsDPEN catalyst, affording a cyclic amine in 88% ee [23] Taken together, these results show that there is a need for more versatile catalysts for DARA, which are active, enantioselective, and effective for both aromatic and aliphatic ketones. We first demonstrated the synergistic effect of the metal-counteranion combination in the asymmetric hydrogenation of acyclic imines [28] Encouraged by these results, we turned our attention to DARA, successfully extending the concept of cooperative catalysis to the reductive amination of both aromatic and aliphatic ketones [30].
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