Improved Methodology for the Preparation of Chiral Amines

1
1g
O
2g HN Ph
81
98
2
1h
O
2h HN Ph
78
98
3
1i
O
2i HN Ph
63
94
1b
O
2b
HN
Ph
78
92
5
4 d 92
O
1a
HN
Ph
2a
79
6
1c
O
2c
HN
Ph
87
80
7
1f
O
2f
HN
Ph
82
e
79
8
1d
O
2d
HN
Ph
83
72
9
1e
O
2e
HN
Ph
82
71
a Ketone (2.5 mmol), dried Yb(OAc) 3 (10 mol %), (S)-α-methylbenzylamine (1.1 equiv), Raney Ni, 0.50 M
(MeOH-THF, 1:1), 12 h. Entries 1-4: T= 50 o C, H 2 pressure = 290 psi (20 bar); entry 5: T= 50 o C, H 2 pressure =
120 psi (8.3 bar), entries 6-9: T= 22 o C, H 2 pressure = 120 psi (8.3 bar). b Isolated yield of both diastereomers
after chromatography. c Determined by GC analysis of the crude product. d Pt-C was used instead of Raney Ni,
T= 50 o C, H 2 pressure = 120 psi. e Non-Yb(OAc) 3 based methods provide 74% de.
Table 6.3 shows the breadth of prochiral ketones that serve as good substrates for our
catalytic method. As might be expected, based on the steric considerations, the
diastereoselectivity of the reductive amination product increases in a fairly undisturbed and
linear progression (72–98%), on changing the R substituent of the 2-alkanone, RC(O)CH 3 ,
from a straight chain alkyl group to those having –γ, -β, and finally -α branching (table 6.3,
122