Improved Methodology for the Preparation of Chiral Amines

2.2.3. Nguyen Special Substrates.
Apart from the classical substrates (structure 1-3, figure 2.1) investigated, substrates which
were tested by Nguyen were unique. By today’s standards the use of stoichiometric quantities
of a chiral reducing agent are not acceptable, but in this case Nguyen has developed a system
capable of accepting a much broader substrate scope and therein lies the significance of his
research. Using stoichiometric amounts of (S)-BINOL/AlMe 3 with isopropanol as a source of
hydrogen to reduce different N-phosphinoyl imines. Subtle difference between small alkyl
groups could be distinguished. They reported 93% ee with 85% yield with imine derived
from 3-octanone. This class of substrates is synthesized utilizing carbanion chemistry because
hydrogen reduction gives low ee (15%). As far as we know this is the only example for
reduction of 3-octanonene utilizing hydrogen with such high enantioselectivity. He tested his
system for other N-phosphinoyl imines and reported high yields and ees (table 2.1). [16]
Table 2.1. Different substrate Categories introduced by Nguyen
entry imine yield(product) ee(%)
1
2
3
4
5
6
1
2
3
4
5
6
Aryl
Ph
Ph
Ph
Ph
1-naphthyl
2-naphthyl
Alkyl
Me
Et
n Pr
i Pr
Me
Me
85%
85%
84%
79%
80%
84%
96%
95%
94%
96%
98%
96%
7
Ph
N
P(O)Ph 2
7 84% 94%
Me
8 8 80% 94%
39