Origins of the Selectivity for Borylation of Primary over Secondary C−H Bonds Catalyzed by Cp*-Rhodium Complexes

Detailed experimental and computational studies of the high selectivity for functionalization of primary over secondary sp3 C−H bonds in alkanes by borane reagents catalyzed by Cp*Rh complexes are reported. Prior studies have shown that Cp*Rh(X)(Bpin) (X = H or Bpin), generated from Cp*Rh(H)2(Bpin)2 and Cp*Rh(H)2(Bpin)3, are likely intermediates in these catalytic reactions. To allow analysis of the system by H/D exchange, the current studies focused on reactions of Cp*Rh(D)2(Bpin)2 through the 16-electron species Cp*Rh(D)(Bpin). Density functional theory (DFT) calculations of the reaction between Cp*Rh(H)(BO2C2H4) and the primary and secondary C−H bonds of propane indicate that the lowest energy pathway for C−H bond cleavage occurs to form an isomer in which the alkyl and boryl groups are trans to each other, while the lowest energy pathway for functionalization of the primary C−H bond occurs by formation of the isomer in which these two groups are cis to each other. The barrier for formation of the rhodium complex by cleavage of secondary C−H bonds is higher than that by cleavage of primary C−H bond. The alkyl intermediates are formed reversibly, and steric effects cause the barrier for B−C bond formation from the secondary alkyl intermediate to be higher than that from the primary alkyl intermediate. Experimental studies are consistent with this computational analysis. H/D exchange occurs between (Cp*d15)Rh(D)2(Bpin)2 and n-octane, indicating that C−H bond cleavage occurs reversibly and occurs faster at primary over secondary C−H bonds. The observation of small amounts of H/D exchange into the secondary C−H bonds of linear alkanes and the clear observation of H/D exchange into the secondary positions of cyclic alkanes without formation of products from functionalization are consistent with the high barrier calculated for B−C bond formation from the secondary alkyl intermediate. A series of kinetic experiments are consistent with a mechanism for H/D exchange between (Cp*d15)Rh(D)2(Bpin)2 and n-octane occurring by dissociation of borane-d1 to form (Cp*d15)Rh(D)(Bpin). Thus, the origin of the selectivity for borylation of primary over secondary C−H bonds is due to the cumulative effects of selective C−H bond cleavage and selective C−B bond formation.