A Highly Enantioselective Homoenolate Michael Addition/Esterification Sequence of Cyclohexadienone-Tethered Enals via NHC Catalysis

Reported here is a highly enantioselective homoenolate Michael addition/esterification sequence of cyclo-hexadienone-tethered enals via N-heterocyclic carbene (NHC) catalysis, affording the enantiopure cis-hydrobenzofurans, cis-hydroindoles, and cis-hydroindenes. The NHC catalyst bearing a nitro group greatly enhances the stereocontrol, and a bulky N-aryl substituent of the triazolium salt in the catalyst is helpful for inhibiting the further aldol condensation after homoenolate Michael addition. The utility of this protocol is highlighted by a gram-scale experiment and versatile downstream transformations.

Automated summary

Here, a highly enantioselective homoenolate Michael addition/esterification sequence of cyclo-hexadienone-tethered enals via N-heterocyclic carbene (NHC) catalysis is reported, leading to the formation of enantiopure cis-hydrobenzofurans, cis-hydroindoles, and cis-hydroindenes. The introduction of a nitro group in the NHC catalyst greatly enhances the stereocontrol, while a bulky N-aryl substituent in the triazolium salt is beneficial for preventing further aldol condensation. The utility of this method is demonstrated through a gram-scale experiment and versatile downstream transformations.