Enantioselective Construction of Vicinal Angular Quaternary Stereocenters Enabled by Strained Cyclobutenones
Peng Yan, Jia Zhang, Licheng Lu, Huayi Fang, Ping Lu
Abstract
Enantioselective construction of contiguous quaternary centers is a daunting challenge in the synthetic community. 2-Substituted 3-(methoxycarbonyl)cyclobutenone, possessing a strained C═C double bond, exhibits both good stability and reactivity. Here, we report a chiral oxazaborolidinium ion (COBI)-catalyzed enantioselective Diels–Alder reaction of 2,3-disubstituted cyclobutenones with a variety of dienes to access bicyclo[4.2.0]octane derivatives, bearing two contiguous angular quaternary centers. Further transformations, including alkylation, cross-coupling reaction and oxyallyl cation reaction afforded the molecules with intriguing structural patterns. The formal total synthesis of estrone was also completed in three steps from enantio-enriched cycloadducts.