Metal ion-catalyzed cycloaddition vs hydride transfer reactions of NADH analogues with p-benzoquinones

1-Benzyl-4-tert-butyl-1,4-dihydronicotinamide (t-BuBNAH) reacts efficiently with p-benzoquinone (Q) to yield a [2+3] cycloadduct (1) in the presence of Sc(OTf)₃ (OTf = OSO₂CF₃) in deaerated acetonitrile (MeCN) at room temperature, while no reaction occurs in the absence of Sc³⁺. The crystal structure of 1 has been determined by the X-ray crystal analysis. When t-BuBNAH is replaced by 1-benzyl-1,4-dihydronicotinamide (BNAH), the Sc³⁺-catalyzed cycloaddition reaction of BNAH with Q also occurs to yield the [2+3] cycloadduct. Sc³⁺ forms 1:4 complexes with t-BuBNAH and BNAH in MeCN, whereas there is no interaction between Sc³⁺ and Q. The observed second-order rate constant (k_obs) shows a first-order dependence on [Sc³⁺] at low concentrations and a second-order dependence at higher concentrations. The first-order and the second-order dependence of the rate constant (k_et) on [Sc³⁺] was also observed for the Sc³⁺-promoted electron transfer from CoTPP (TPP = tetraphenylporphyrin dianion) to Q. Such dependence of k_et on [Sc³⁺] is ascribed to formation of 1:1 and 1:2 complexes between Q^•- and Sc³⁺ at the low and high concentrations of Sc³⁺, respectively, which results in acceleration of the rate of electron transfer. The formation constants for the 1:2 complex (K₂) between the radical anions of a series of p-benzoquinone derivatives (X - Q^•-) and Sc³⁺ are determined from the dependence of k_et on [Sc³⁺]. The K₂ values agree well with those determined from the dependence of k_obs on [Sc³⁺] for the Sc³⁺-catalyzed addition reaction of t-BuBNAH and BNAH with X - Q. Such an agreement together with the absence of the deuterium kinetic isotope effects indicates that the addition proceeds via the Sc³⁺-promoted electron transfer from t-BuBNAH and BNAH to Q. When Sc(OTf)₃ is replaced by weaker Lewis acids such as Lu(OTf)3, Y(OTf)3, and Mg(ClO₄)₂, the hydride transfer reaction from BNAH to Q also occurs besides the cycloaddition reaction and the k_obs value decreases with decreasing the Lewis acidity of the metal ion. Such a change in the type of reaction from a cycloaddition to a hydride transfer depending on the Lewis acidity of metal ions employed as a catalyst is well accommodated by the common reaction mechanism featuring the metal-ion promoted electron transfer from BNAH to Q.