Reductive and Oxidative Bond-cleavage Reactions

The V0(0Et)Cl2-catalyzed reaction of styrenes with molecular oxygen in the presence of a co-reductant such as PhSiHs results in oxidation-reduction and oxidative bond cleavage of styrenes (Scheme 2.42) [99]. Coordination of the A -heterocyclic multidentate ligand, the 2,6-pyridinedicarboxantide of histamine (BIPA), increases the relative yield of the latter product. The Mn(OAc)2-catalyzed oxidation of a-methylstyrene in the presence of BIPA under molecular oxygen selectively leads to 2-phenyl-2-propanol via oxidation-reduction. BIPA is also useful as a ligand in the Mn(OAc)2-catalyzed epoxidation of a-methylstyrene with PhlO. 

As depicted in Scheme 1, reductive and oxidative cleavages may follow either a concerted or a stepwise mechanism. How the dynamics of concerted electron transfer/bond breaking reactions (heretofore called dissociative electron transfers) may be modeled, and particularly what the contribution is of bond breaking to the activation barrier, is the first question we will discuss (Section 2). In this area, the most numerous studies have concerned thermal heterogeneous (electrochemical) and homogeneous reactions. 

For the oxidative addition pathway, however, it is not obvious why the C-H bond cleavage reaction should be more facile if the hydrocarbon first binds in the coordination sphere of the metal (Scheme 5, c). One argument could be that the equilibrium between the Pt(II) alkane complex and the five-coordinate Pt(IV) alkyl hydride has an intrinsically low activation barrier. Insight into this question together with detailed information about the mechanisms of these Pt(II) a-complex/Pt(IV) alkyl hydride interconversions has been gained via detailed studies of reductive elimination reactions from Pt(IV), as discussed below. 

Figure 16.2 Thermochemical cycles involving the heterolytic and homolytic cleavages of the R-X bond, and reduction or oxidation processes. The reaction numbers are the same as in figure 16.1.

A less common reactive species is the Fe peroxo anion expected from two-electron reduction of O2 at a hemoprotein iron atom (Fig. 14, structure A). Protonation of this intermediate would yield the Fe —OOH precursor (Fig. 14, structure B) of the ferryl species. However, it is now clear that the Fe peroxo anion can directly react as a nucleophile with highly electrophilic substrates such as aldehydes. Addition of the peroxo anion to the aldehyde, followed by homolytic scission of the dioxygen bond, is now accepted as the mechanism for the carbon-carbon bond cleavage reactions catalyzed by several cytochrome P450 enzymes, including aromatase, lanosterol 14-demethylase, and sterol 17-lyase (133). A similar nucleophilic addition of the Fe peroxo anion to a carbon-nitrogen double bond has been invoked in the mechanism of the nitric oxide synthases (133). 

Similar redox-combined processes have been reported. For example, it has been clarified by control experiments using a photoirradiated semiconductor electrode that the photocatalytic production of indazoles from substituted azobenzenes is based on the condensation of two intermediates formed through oxidation and reduction.38 40) In the case of oxidation of substituted olefins a similar redox combined mechanism is assumed cation and anion radicals are formed by the reaction of olefin with positive hole and of 02 with excited electron, respectively, and they react to produce a 4-membered ring intermediate, a dioxethane, to undergo bond cleavages into the desired products.4l) In the photocatalytic reactions, a positive hole and excited electron must react at the neighboring surface sites of a small semiconductor particle, enabling the combination of reduction and oxidation without the addition of an electrolyte, which is an indispensable component in electrolysis. However, in the particulate system the recombination of positive hole and electron is also likely, as well as... 

A subsequent study ° from the Arnold group showed an intriguing stereoelectronic effect in oxidative benzylic carbon-hydrogen bond cleavage reactions of substrates 8 and 9 (Scheme 3.7). In this study, electron transfer reactions were conducted in the presence of a nonnucleophilic base. Radical cation formation also weakens benzylic carbon-hydrogen bonds, thereby enhancing their acidity. Deprotonation of benzylic hydrogens yields benzylic radicals that can be reduced by the radical anion of dicyanobenzene to form benzylic anions that will be protonated by solvent. This sequence of oxidation, deprotonation, reduction, and protonation provides a sequence by which epimerization can be effected at the benzylic center. In this study, tram isomer 10 showed no propensity to isomerize to cis isomer 11 (equation 1 in Scheme 3.7), but 11 readily converted to 10 (equation 2 in Scheme 3.7). The reactions were repeated in deuterated solvents to assure that these observations resulted from kinetic rather than thermodynamic factors. Trans isomer 9 showed no incorporation of deuterium (equation 3 in Scheme 3.7) whereas cis isomer 11 showed complete deuterium incorporation. The authors attributed this difference in reactivity to... 

As mentioned above, treatment of the aldol adducts 150 a/b with NMO produced the phenol 152. The interesting oxidation properties of NMO had previously been investigated by Sulikowski et al. on the model compound 157 [85] (Scheme 40). They observed the formation of the hemiacetal 159 in 60% yield and assumed attack of the nucleophilic N-oxide on the quinonemethide tautomer 158 (or on the anion of 158). A related reaction was observed in our group in which the diol 94 was methoxylated at C-6 to 95 by treatment with methoxide ions [82] (Scheme 27). An internal redox step is postulated to account for the reductive 0-N-bond cleavage with concomitant oxidation of the hydroquinone back to the quinone. Without the presence of perruthenate, aromatization with formation of a C-5 phenolic hydroxy group was observed, a reaction later exploited in the synthesis of angucycline 104-2 [87] (see Scheme 49). Thus, based on similar mechanistic principles, the chemical results of the NMO oxidations were quite different compound 147 gave the C-6 phenol 152 [86] whereas 157/158 were converted to the C-5 phenol 160 [85]. 

This mechanistic pathway is in direct competition with the reverse order of reductions (first nitro-reduction), as the resulting nitrosovinyl species 75 may isomerize to 76, cyclize to 77 and cyclorevert orthogonally. This liberates hydrogen cyanide in a C—C-bond cleavage reaction and amounts to a net oxidation... 

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