Access to Chiral Tertiary α-Hydroxyesters via Rhodium-Catalyzed Enantioselective Allylation of α-Ketoesters

Molecules containing a tertiary α-hydroxy carbonyl moiety are vital building blocks for synthesizing pharmaceuticals and natural products. In this study, we present an efficient rhodium(I)-catalyzed enantioselective allylation of α-ketoesters, providing a direct route to tertiary α-hydroxy esters. Operating at 5 °C, the method employs various α-ketoesters and allylBpin reagents to deliver the enantiomerically enriched tertiary homoallylic α-hydroxyesters bearing quaternary centers in high yields (up to 99%), excellent enantioselectivity (up to 98% ee), and diastereoselectivity (dr > 20:1). Demonstrating its synthetic utility, this protocol enables a five-step linear synthesis of lactone 13—a key precursor for anti-HIV and anticancer nucleoside analogues—from homoallylic alcohol 5af in a remarkable 85% overall yield.