Enantioselective and stereodivergent hydromonofluoroalkylation of conjugated and remote dienes
Qi-Ying Liao, Chao Ma, Yuchao Wang, Shao‐Qian Yang, Jiang-Shan Ma, Zhi‐Tao He
Abstract
Because of the widespread applications of optically active alkyl fluorides in medicinal and agro chemicals , enantioselective and even stereodivergent construction of alkyl fluorides remains highly desirable but underdeveloped. Transition-metal-catalyzed asymmetric hydrofluoroalkylation of readily available dienes represents a novel route to achieve this goal, yet receives scarce study. Here we report an intriguing palladium-catalyzed enantioselective hydromonofluoroalkylation reaction of conjugated dienes. Both monosubstituted and internal dienes proceed well with the transformation and furnish alkyl fluorides in generally >80% yield and >90% ee . A stereodivergent hydromonofluoroalkylation protocol via Pd/Cu co-catalysis is also established for the access to all four stereoisomers of corresponding moieties bearing a fully-substituted F-stereogenic center and vicinal tertiary carbon center. In addition, asymmetric migratory hydromonofluoroalkylation of skipped dienes is developed to realize the direct allylic C H fluoroalkylation. A compound library of enantioenriched cyclic fluorides is thus built to highlight the transformation potential of present methodology.