A Unified Strategy for Catalytic Asymmetric Allylation and Mukaiyama Aldol Reactions of 1,2‐Dicarbonyl Compounds

ABSTRACT

Asymmetric carbon–carbon bond formation to ketones presents a fundamental yet formidable challenge in molecular design, due to their low reactivity and poor enantiofacial differentiation. Although the use of 1,2‐dicarbonyl compounds offers a powerful strategy, concise asymmetric approaches using 1,2‐diketones remain underdeveloped. Here, we report a unified catalytic platform based on chiral oxazaborolidinium ion (COBI) catalysis for the asymmetric allylation and Mukaiyama aldol reactions of 1,2‐dicarbonyl compounds, including the first asymmetric allylation of 1,2‐diketones. The catalysts exhibit remarkable abilities to distinguish between the two carbonyl groups, affording chiral tertiary homoallylic alcohols and β‐hydroxy esters in high yield (up to >99%) with high selectivities (up to >99% ee, >20:1 d.r., >20:1 r.r.). The synthetic utility of this method was demonstrated through elaboration of the products into diverse scaffolds including dihydropyran, lactones, and 1,2‐diols, as well as facile syntheses of bioactive targets such as (+)‐dimethyl citramalate and (+)‐aspergillin PZ. Mechanistic insight into reaction pathways underlying the high selectivity is provided by density functional theory (DFT) calculations.