Introduction
As versatile building blocks and synthetic intermediates, chiral amines
play important roles in the construction of numerous valuable molecules.
According to statistics, more than 40% of the top 200 listed small
molecule drugs contain at least one chiral amine subunit in their
structures. Therefore, the development of general and efficient methods
to prepare chiral amines has been a major focus in both academia and
industry.[1] In the process of pursuing this goal,
catalytic asymmetric hydrogenation (AH) has gradually emerged as the
most industrially feasible option due to its high efficiency, cost
competitiveness and environmental
friendliness.[2,3] Until now, hundreds of chiral
transition metal catalysts have been developed and successfully applied
in the asymmetric hydrogenation of thousands of structurally differentN -containing substrates. The most representative research is the
enantioselective synthesis of α -chirogenic amines by the
catalytic asymmetric hydrogenation of enamines and imines (Scheme 1A),
which was awarded the Nobel Prize in Chemistry of 2001 and has been used
in several impressive industrial productions.[3]By contrast, the number of studies on the hydrogenative synthesis ofβ -chirogenic amines decreases significantly. One route via the
asymmetric hydrogenation of β -branched allylic amines is
difficult due to the relatively low stability of the macrocyclic
chelating intermediate.[4] Another route via the
asymmetric hydrogenation of β -branched enamines is also difficult
due to a relatively poor stereocontrol for the distinct substituted
environment (Scheme 1B).[5] Therefore, it can be
envisaged that the construction of γ -chirogenic amines via the
asymmetric hydrogenation of γ -branched allylamines, which
contains either of the above-mentioned difficulties for remote control,
is a greater challenge (Scheme 1C). Until now, there have been no
universal solutions with regards to this topic,[6]in spite of γ -chirogenic amines being required for the synthesis
of important pharmaceuticals such as the antidepressant drugs
Atomoxetine, Fluoxetine and Duloxetine, and the anti-muscarinic drug
Tolterodine (Figure 1).
Scheme 1. Asymmetric hydrogenation for the synthesis of chiral
amines.
Figure 1. The importance of γ -chirogenic amines.