Short and Atom-Economic Enantioselective Synthesis of the σ-Receptor Ligands ()- and ()-Fluspidine-Important Tools for Positron Emission Tomography Studies.

Aryl bromides and bearing an alkynyl substituent in the o-position reacted with -butyllithium and 1-benzylpiperidin-4-one in a one-pot Domino reaction to form ester and aldehyde , respectively. Enantiomeric alcohols ()- and ()- were obtained by conjugate NaBH reduction of α,β-unsaturated ester in the presence of chiral cocomplexes (,)- and (,)-. Starting from orthoester , the precursors ()- and ()- for the synthesis of fluspidine enantiomers ()-/F- and ()-/F- were obtained in only two reaction steps without additional steps for N-protection in an atom-economic manner in 95.6% ee and 97.2% ee, respectively.