Theoretical Study of Rhodium‐Catalyzed C−C Activation of Cyclobutanones: Origin of Ligand‐Controlled Product Selectivity

Abstract Cyclobutanone C−C activation with a Rh(I) catalyst has great potential for the synthesis of fused‐ and bridged‐ring systems. However, this synthetic application is greatly limited because of the direct CO extrusion from cyclobutanone, which leads to formation of cyclopropane as a byproduct. The calculations rationalize the experimental puzzles: why PMe2Ph and XPhos ligands can prevent cyclopropane formation for C2‐ and C3‐substituted cyclobutanone, respectively. More importantly, we enriched ligand computationally to exemplify how to develop new ligands. The small monodentate or bidentate phosphine ligand can favor [4+2] cycloaddition over cyclopropanation in the C2‐substituted cyclobutanone system. For the C3‐substituted cyclobutanone system, [4+2–1] cycloaddition is favored and cyclopropanation can be avoided when the large monodentate phosphine ligand is present. The different ligand requirements for C2‐ and C3‐substituted cyclobutanones are attributed to different mechanisms.