Improved Methodology for the Preparation of Chiral Amines

of imine reduction in the past eight years. Of course in the nineties great achievements were
accomplished for complete picture please refer to the following review. [2]
2.2. Asymmetric Reduction of N-Phosphinoyl Imines
Of the useful imine substrates examined to date, N-phosphinoyl imines hold the advantage of
being reduced with high yields and ees. The steric bulk of the diphenylphosphine group
affects the geometric form of imine (only anti isomer is obtained). [5] To access N-phosphinoyl
imines researchers universally begin with a ketone and convert it to an oxime (high yield).
Oximes are readily prepared from ketones and HCl.H 2 NOH, pyridine in ethanol by mixing
1.0 equiv of ketone and 1.1 hydroxyl amine hydrochloride and 1.1 equiv of pyridine. [6]
Treatment of the oxime with chlorodiphenylphosphine [Ph 2 P(O)Cl] at –45-78 °C provides the
N-phosphinoyl imine in mediocre to good yields. For example aryl alkyl N-phosphinoyl
imines provide yield in the range of 40-70%, while alkyl alkyl N-phosphinoyl imines provide
yields in the range of 50-70%. The product is purified with column chromatography (scheme
2.1). [7]
2.2.1. Synthesis of N-Phosphinoyl Imines.
high
yield
N
OH
R 1 R 2
Ph 2 P(O)Cl
Et 3 N, -45 °C
O
R 1 R 2
+
H 2 N
O
P Ph
Ph
N
R 1 R 2
CH 2 Cl 2
P(O)Ph 2 P(O)Ph2
reduction
high yield
HN
R 1
* R 2
high
NH 2
yield R 1 * R 2
R 1 = aryl, alkyl, heterocylic
R2 = alkyl
1- Ph 2 P(O)Cl, CH 2 Cl 2 ,-78°C
2- hydrolytic work-up
NOH
H 2 NOH
HCl
O
Scheme 2.1. General Strategies for Synthesis of N-Phosphinoyl Imines.
35