Steric‐Driven Pathway Switch in Rhodium‐Catalyzed Indole C─H Functionalization With Allenes: A Mechanistic DFT Study

Density functional theory (DFT) calculations have been performed to elucidate the steric‐controlled divergent reaction pathways in rhodium(III)‐catalyzed C─H functionalization of indoles with di‐ and trisubstituted allenes. For disubstituted allenes, rhodium preferentially binds to the terminal allenic carbons to form a π‐allylrhodium(III) intermediate ( Path I ), which undergoes facile β ‐O elimination to afford E ‐configured 1,3‐diene products with exclusive stereoselectivity. Although carborhodation shows no obvious regioselectivity between terminal and central allenic carbons, the much lower energy barrier of β ‐O elimination relative to protodemetalation dictates the exclusive occurrence of Path I . In sharp contrast, trisubstituted allenes direct rhodium to the central allenic carbon ( Path II ) to avoid severe steric repulsions, and the subsequent protodemetalation yields allylation products exclusively. Further frontier molecular orbital (FMO) and natural population analysis (NPA) reveal that steric effects overwhelmingly dominate the regioselectivity over electronic factors. These results fully rationalize the experimentally observed pathway switch and provide a mechanistic framework for the rational design of selective indole C─H functionalization reactions.