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.