Constructing chiral bicyclo[3.2.1]octanes via palladium-catalyzed asymmetric tandem Heck/carbonylation desymmetrization of cyclopentenes

Transition-metal-catalyzed tandem Heck/carbonylation reaction has emerged as a powerful tool for the synthesis of structurally diverse carbonyl molecules, as well as natural products and pharmaceuticals. However, the asymmetric version was rarely reported, and remains a challenging topic. Herein, we describe a palladium-catalyzed asymmetric tandem Heck/carbonylation desymmetrization of cyclopentenes. Alcohols, phenols and amines are employed as versatile coupling reagents for the construction of multifunctional chiral bicyclo[3.2.1]octanes with one all-carbon quaternary and two tertiary carbon stereogenic centers in high diastereo- and enantioselectivities. This study represents an important progress in both the asymmetric tandem Heck/carbonylation reactions and enantioselective difunctionalization of internal alkenes. Tandem Heck/carbonylation reaction gives access to ubiquitous carbonyl molecules, however the asymmetric version is rarely studied. Here, the authors synthesize chiral bicyclo[3.2.1]octanes with a palladium-catalyzed asymmetric tandem Heck/carbonylation desymmetrization of cyclopentenes with alcohols, phenols and amines.