Pd‐Catalyzed Decarboxylative Asymmetric Protonation of Sterically Hindered α‐Aryl Lactones and Dihydrocoumarins

Abstract

AbstractPd‐catalyzed decarboxylative asymmetric protonation (DAP) has been developed for sterically hindered α‐aryl lactone and dihydrocoumarin substrates. Optimization studies were conducted using δ‐lactone‐ and dihydrocoumarin‐derived α‐aryl, β‐oxo‐allyl esters with 2,4,6‐trimethoxyphenyl as the aryl substituent. In the absence of a chiral P,N‐ligand, (1R,2S)‐(−)ephedrine, a cheap and readily available chiral proton donor, induced enantioselectivities of up to 92% ee and 88% ee with lactone and dihydrocoumarin substrates, respectively. Bulky aryl groups containing di‐ortho substitutions and naphthyl groups gave the highest enantioselectivities of up to 92% and 86%, respectively. A stereochemical rationale is proposed to explain the preferred sense of asymmetric induction.magnified image