Improved Methodology for the Preparation of Chiral Amines

Scheme 3.9. Synthesis of (S)-Metolachlor
One of the significant examples for the asymmetric reductive amination was developed by
Zhang. The substituted aromatic and heteroaromatic ketones (acetophenone and substituted
acetophenone) were used as examples and produced ee in the range of 89-96% and >99%
yield with 1.0 mol % of Ir-(S,S)-f- Binaphane catalyst (scheme 3.10). According to the report,
Ti(OiPr) 4 did not have any effect on the enantioselectivity but facilitates producing imine in
situ from a hemiaminal titanate intermediate (as discussed earlier). He found that the presence
of iodine is essential for the reaction to proceed as the oxidative addition of I 2 to the Ir I
precursor generates Ir III complex which is then coordinated with hydrogen forming Ir III -H
complex to which imine is coordinated and starting the catalytic cycle. Despite these
fascinating ees and yields for the aromatic ketones, this system failed to reductively aminate
aliphatic ketones. High catalyst loading and high hydrogen pressure (69 bar) are other
limitations of this methodology. [44]
Ar
O
R
Ir-(S,S)-f-Binaphane (1.0 mol%)
10% I 2 /Ti(OiPr) 4 (1.5 equiv.)
p-anisidine (1.2 equiv.)
H 2 (69 bar), RT
HN
∗
Ar R
OMe
P
Fe
P
Ir-(S,S)-f-Binaphane
Scheme 3.10. Binaphane Iridium Catalyst In Asymmetric Reductive Amination.
61