Enantioselective Synthesis of <i>cis</i>-3-Fluoropiperidin-4-ol, a Building Block for Medicinal Chemistry

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.