Metal Ion-Catalyzed Cycloaddition vs Hydride Transfer Reactions of NADH Analogues with p-Benzoquinones

Abstract

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 = OSO(2)CF(3)) in deaerated acetonitrile (MeCN) at room temperature, while no reaction occurs in the absence of Sc(3+). 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 Sc(3+)-catalyzed cycloaddition reaction of BNAH with Q also occurs to yield the [2+3] cycloadduct. Sc(3+) forms 1:4 complexes with t-BuBNAH and BNAH in MeCN, whereas there is no interaction between Sc(3+) and Q. The observed second-order rate constant (k(obs)) shows a first-order dependence on [Sc(3+)] 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 [Sc(3+)] was also observed for the Sc(3+)-promoted electron transfer from CoTPP (TPP = tetraphenylporphyrin dianion) to Q. Such dependence of k(et) on [Sc(3+)] is ascribed to formation of 1:1 and 1:2 complexes between Q(*)(-) and Sc(3+) at the low and high concentrations of Sc(3+), respectively, which results in acceleration of the rate of electron transfer. The formation constants for the 1:2 complex (K(2)) between the radical anions of a series of p-benzoquinone derivatives (X-Q(*)(-)) and Sc(3+) are determined from the dependence of k(et) on [Sc(3+)]. The K(2) values agree well with those determined from the dependence of k(obs) on [Sc(3+)] for the Sc(3+)-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 Sc(3+)-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(ClO(4))(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.

Reactivity and Biological Activity of the Marine Sesquiterpene Hydroquinone Avarol and Related Compounds from Sponges of the Order Dictyoceratida

“…References to both opposing views are presented in several stimulating publications but differences in interpretation still persist [27][28][29][30][31][32][33][34][35].…”

“…Still, we believed that evidence of semiquinone radical formation in biochemical reactions was insufficient. It seemed that the investigation of a relevant redox process such as the reaction of naturally occuring quinones with NAD(P)H models under conditions aimed to mimic those in biological systems, might be an adequate reaction although earlier examinations led to contradictiory conclusions (see above, [27][28][29][30][31][32][33][34][35]). …”

Recent advances in 1,4-benzoquinone chemistry

“…The mechanistic and kinetic aspects of competing metal-ion catalyzed cycloaddition and hydride transfer reactions of NADH analogues with 1,4-benzoquinones have been studied by Fukuzumi et al 292 1-Benzyl-4-tbutyl-dihydronicotinamide (211) reacts efficiently with 1,4-benzoquinone (1) to yield a [2+3] cycloadduct (212) in the presence of Sc(OSO 2 CF 3 ) 3 in deaerated acetonitrile at room temperature (Scheme 54), while no reactions occur in the absence of Sc 3+ .…”

Catalytic control of electron-transfer processes

“…In the presence of Sc(OTf) 3 , the Lewis acidity of which is much stronger than Mg 2+ , however, cycloaddition reaction of t-BuBNAH with Q rather than hydride transfer occurs efficiently at 298 K (eq. 5) [26]. Kinetic comparison between the Sc 3+ -catalyzed cycloaddition not only the electron and the Sc 3+ -promoted electron-transfer reduction of Q together with the absence of the deuterium kinetic isotope effects indicates that the addition reaction proceeds via the Sc 3+ -promoted electron transfer from t-BuBNAH and BNAH to Q.…”