The origin of the ligand-controlled regioselectivity in Rh-catalyzed [(2 + 2) + 2] carbocyclizations: steric stereoelectronic effects.

Density functional theory calculations demonstrate that the reversal of regiochemical outcome of the addition for substituted methyl propiolates in the rhodium-catalyzed [(2 + 2) + 2] carbocyclization with PPh and ()-xyl-binap as ligands is both electronically and sterically controlled. For example, the ester functionality polarizes the alkyne π* orbital to favor overlap of the methyl-substituted terminus of the alkyne with the p-orbital of the alkenyl fragment of the rhodacycle during alkyne insertion with PPh as the ligand. In contrast, the sterically demanding xyl-binap ligand cannot accommodate the analogous alkyne orientation, thereby forcing insertion to occur at the sterically preferred ester terminus, overriding the electronically preferred orientation for alkyne insertion.