(-)-sparteine-mediated asymmetric intramolecular carbolithiation of alkenes: Synthesis of enantiopure cyclopentanes with three consecutive stereogenic centers

Abstract

An asymmetric intramolecular carbolithiation reaction was developed by combining the (-)-sparteine-mediated enantiotopos-differentiating deprotonation and the anionic 5-exo-trig cyclization. Achiral 6-phenylhex-5- enyl carbamates were efficiently cyclized furnishing regio-, diastereo- (dr >99:1), and enantioselectively (er >98:2) 1,2-trans-substituted cyclopentanes. The intermediate primary benzylic lithium-carbanion pairs were - in spite of their configurative lability - diastercoselectively substituted by versatile electrophiles creating a third consecutive stereogenic center. Additionally, some 4-functionalized 6-phenylhex-5-enyl carbamates were also cyclized in high yield to provide enantiomerically pure cyclopentanes incorporating three adjacent stereogenic centers.