Organocatalytic Enantioselective Desymmetrization Cascade for the Construction of Functionalized Oxabicyclo[3.3.1]nonanes

The construction of stereochemically enriched molecules from readily accessible meso and prochiral precursors via catalytic enantioselective desymmetrization represents a powerful synthetic strategy. Herein, we report an efficient enantioselective Michael/oxa-Michael cascade reaction between C4-functionalized meso -2,5-cyclohexadienones and β-ketoesters, catalyzed by a Takemoto chiral squaramide. This protocol enables the efficient construction of densely functionalized oxabicyclo[3.3.1]nonane frameworks bearing two or three stereogenic centers, with good to excellent diastereo- and enantioselectivities. Furthermore, the method is amenable to scale-up and offers opportunities for late-stage functionalization.