posted on 2013-09-06, 00:00authored bySimon J. Shaw, Dane A. Goff, Luke A. Boralsky, Mark Irving, Rajinder Singh
The first enantioselective route
to both enantiomers of cis-1-Boc-3-fluoropiperidin-4-ol,
a highly prized building
block for medicinal chemistry, is reported. An enantioselective fluorination
is employed, taking advantage of the methodology reported by MacMillan,
which uses a modified cinchona alkaloid catalyst. In studying the
fluorination reaction, we have shown that the catalyst can be replaced
by commercially available primary amines, including α-methylbenzylamine,
with similar levels of enantioselectivity. The piperidinols are readily
crystallized to obtain enantiopure material.