Enantioselective Construction of Vicinal Angular Quaternary Stereocenters Enabled by Strained Cyclobutenones

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.