The
base
n
-BuLi with sparteine allows a kinetic
resolution of
N
-Boc-2-aryl-4-methylenepiperidines.
The 2,2-disubstituted products and recovered starting materials were
isolated with high enantiomeric ratios. From VT-NMR spectroscopy and
DFT studies, the rate of rotation of the
N
-Boc group
is fast. Lithiation and trapping of the enantioenriched starting materials
gave 2,2-disubstituted piperidines with retention of stereochemistry.
Functionalization of the 4-methylene group led to a variety of 2,4-disubstituted
piperidines without loss of enantiopurity that could be useful building
blocks for drug discovery.