CuH-Catalyzed Enantioselective Desymmetrization of Cyclic 1,3-Diketones

Herein, we report a CuH-catalyzed asymmetric desymmetrization of prochiral cyclopentane-1,3-diones to access cyclic 3-hydroxy ketones having an all-carbon quaternary center with high diastereoselectivity via hydrosilylation using PMHS as an inexpensive hydride source. This reaction displays high functional group tolerance including reducible alkyne, alkene, and ester groups with a broad substrate scope. The importance of chiral cyclic 3-hydroxy ketone building blocks was also demonstrated through the synthesis of (-)-estrone, the toxicodenane E core, and fused indoles.

Automated summary

In this study, a CuH-catalyzed asymmetric desymmetrization reaction of prochiral cyclopentane-1,3-diones was reported. By using PMHS as a cost-effective hydride source, cyclic 3-hydroxy ketones with an all-carbon quaternary center could be synthesized with high diastereoselectivity. The reaction demonstrated excellent functional group tolerance, including reducible alkyne, alkene, and ester groups, and showed a broad substrate scope. The importance of chiral cyclic 3-hydroxy ketone building blocks was further demonstrated through the synthesis of (-)-estrone, the toxicodenane E core, and fused indoles.