Enantiodivergent Synthesis of 3‐Vinylphthalides via Rh‐Catalyzed C─H Annulation: Experimental and Computational Studies

Asymmetric transition metal catalysis represents the most reliable method for the chiral induction in organic scaffolds and to synthesize a wide array of valuable 3D-molecules. However, accessing both enantiomers of the chiral molecules from a catalyst(s) having the same chirality through ingenious stereo-control has remained a highly demanding task. Herein, we disclose the catalytic enantiodivergent synthesis of 3-vinylphthalides from arylcarboxylic acids and cyclopropenes, an efficient surrogate for vinylcarbenes. Through engineering the chiral cyclopentadienylrhodium(III) catalysts, both enantiomers have been achieved with excellent yield and enantioselectivity via regioselective C─H bond functionalization using a weakly coordinating directing group and asymmetric [4+1]-annulation. Experimental and computational investigations revealed the mechanism of the oxidative annulation and enantiodetermining ring-opening isomerization of cyclopropenes, which is governed by the stereoselective cleavage of the C─C bond. The present study opens a new avenue in asymmetric C─H bond functionalization and allows access to both enantiomers of the target molecules without altering the chirality of the ligand.