Asymmetric
reductive amination (ARA) of a prochiral carbonyl compound
with an amine using a H2/hydrogen surrogate is a concise
and operationally simple method for the synthesis of chiral amines.
ARA proceeds via condensation of a carbonyl group with an amine/ammonia
followed by the enantioselective reduction of the generated intermediate.
The activation of reductant and stereoselective transfer of hydrogen
to intermediate imine/enamine is often mediated by a chiral transition
metal catalyst. Considering the wide applications of enantiopure amines
in pharmaceuticals, agrochemicals, and materials, the development
of effective catalysts for ARA has been intensively pursued in the
last two decades. Since the first report by Blaser in 1999, this key
research area has grown significantly in recent years, as reflected
by the advances in catalyst design, diversifying substrate scope and
better mechanistic understanding. Several highly efficient and general
ARA methodologies applicable to challenging carbonyl and amine partners
have been demonstrated, providing ready access to a variety of enantiopure
amines. In this Review, we present the recent progress in ARA featuring
diverse carbonyl and amine partners employing transition metal-catalysts.
This Review provides an organized and critical discussion on catalyst
engineering and evolution, expanding susbstrate scope and mechanistic
insights. To conclude, the remaining challenges and opportunities
in ARA are also highlighted.