Enantioselective Construction of Vicinal Angular Quaternary Stereocenters Enabled by Strained Cyclobutenones

Enantioselective construction of contiguous quater-nary centers is a daunting challenge in the synthetic community. Substituted 3-(methoxycarbonyl)cyclobutenone, possessing 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-disubsti-tuted 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.

Automated summary

In this study, we report a new method for enantioselective Diels-Alder reaction catalyzed by a chiral catalyst COBI, which enables the asymmetric reaction of 2,3-disubstituted cyclobutenones with various dienes. This method successfully synthesizes bicyclo[4.2.0]octane derivatives with two contiguous angular quaternary centers, demonstrating intriguing structural patterns.