Kinetic Resolution of Nitrogen Heterocycles using Chiral Organolithium Chemistry

Abstract
The kinetic resolution and α-deprotonation of nitrogen–containing heterocycles using
organolithium chemistry has been an important area of work in the Coldham group over the
last decade. Some successful research published has been focussed around the kinetic
resolution reactions of N-Boc-2-arylpiperidines and N-Boc-2-aryltetrahydroquinolines.
This report describes the extension of this chemistry to different heterocycles, namely 1,3-
oxazinane A, benzoxazines B, quinoxalines C, and indoline D derivatives (Figure A).
Figure A
The kinetic resolutions were attempted using a chiral base complex (n-BuLi/(+)-sp), which led
to the recovered starting materials in good yields and excellent enantiomer ratios (Figure B).
Figure B
It was possible to remove the Boc group using acid (TFA) to give the corresponding secondary
amine with the enantiopurity being maintained (Figure C).II