Conjugate Addition of 2- and 4-Pyridylcuprates:  An Expeditious Asymmetric Synthesis of Natural (−)-Evoninic Acid

The scope and limitations of the conjugate addition of 2- and the first 4-pyridyl Gilman homocuprates to various α,β-unsaturated Michael acceptors are delineated. The conjugate addition of the cuprate of 2-bromo-3-methylpyridine to (E)-methyl crotonate then diastereoselective enolate alkylation and lipase-mediated enantioselective ester hydrolysis have enabled an efficient four-step first asymmetric synthesis of the Celastraceae sesquiterpenoid esterifying ligand (−)-(1‘S,2‘S)-evoninic acid.