Formation of contiguous quaternary and tertiary stereocenters by sequential asymmetric conjugate addition of Grignard reagents to 2-substituted enones and Mg-enolate trapping.
Herein a comprehensive study is provided on the asymmetric conjugate addition (ACA) of Grignard reagents to α-substituted cyclic enones. After the elucidation of the optimal experimental conditions, the scope of Grignard reagents and Michael acceptors was examined. Whereas secondary Grignards gave better enantioselectivities with 2-cyclopentenones, both linear and branched Grignard reagents were tolerated for the ACA to 2-methylcyclohexenone. The sequential ACA-enolate trapping, which leads to quaternary stereocenters, was then studied. Thus, many electrophiles have been tested, thereby giving rise to highly functionalized cyclic ketones with contiguous α-quaternary and β-tertiary centers. The present technique is believed to bring a new approach to versatile terpenoid-like skeletons of bioactive natural products. Straightforward derivatizations of enantioenriched saturated cyclic ketones further support the potential of the present methodology in synthesis.
Département de chimie Organique, Science II, Université de Genève, Quai Ernest Ansermet 30, 1211 Genève 4 (Switzerland).
Nicolas
N
Germain
Département de chimie Organique, Science II, Université de Genève, Quai Ernest Ansermet 30, 1211 Genève 4 (Switzerland). alexandre.alexakis@unige.ch.
Alexandre
A
Alexakis
Grignard reagents; addition; copper; enantioselectivity; natural products