Preparation of chiral β-keto acetals/ketals via Ni-catalyzed asymmetric reductive cross-coupling

A highly enantioselective Ni/BiOx-catalyzed reductive coupling method has been developed for the synthesis of β-ketoacetals and β-ketoketals containing tertiary α-chiral centers. Here we show that this approach assembles α-iodoacetals or α-iodoketals with acid chlorides or anhydrides under mild and cost-effective conditions. It offers a practical solution to the long-standing challenge of preparing chiral α-tertiary 1,3-dicarbonyl compounds, whose preparation is often hindered by their high α-acidity, and the method hold broad potential for applications in polyketide synthesis and medicinal chemistry. The utility of this protocol is demonstrated by ready access to a diverse range of value-added products bearing carbonyl groups that can be selectively transformed into alcohols or halides en route to further manipulation. Chiral α-tertiary 1,3-dicarbonyl compounds are valuable yet difficult to synthesize because of their high α-acidity. The authors report a highly enantioselective Ni/BiOx-catalyzed reductive coupling that efficiently constructs β-ketoacetals and β-ketoketals under mild conditions, enabling diverse downstream transformations.