Regioselectivity and Kinetics of Hydride Transfer in Substituted 1-Benzyl-3-quinolinecarboxamide Redox Reactions

A systematic study on the factors that affect the regioselectivity and rate of hydride transfer in systems involving l-benzyl-4-methyl-3-quinolinecarboxamides as donors or acceptors is reported. The study reports two major findings: (1) Hydride transfers from borohydride or l-propyl-l,4-dihydronicotinamide to l-benzyl-4-methyl-3-quinolinecarboxamide cation display distinct regioselective patterns—borohydride results in hydride transfer to the 2-position of the acceptor and dihydronicotinamide results in hydride transfer to the 4-position of the acceptor. (2) Substitution of the 4-hydrogen by a methyl group on either the oxidant or reductant quinoline lowers the rate constants for hydride transfer by a factor of over 2000. When methyl replaces hydrogen in both the oxidant and reductant, the rate constant for hydride transfer is lowered by a factor of over 5 000 000. These observations are interpreted in terms of a two-step mechanism: (1) formation of a π-complex between the oxidant and reductant stabilized by charge-transfer interactions and (2) rate-determining hydride transfer within the complex.