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

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.