Concerted homolysis

Some systematic studies on the different reaction schemes and how they are realized in organic reactions were performed some time ago [18]. Reactions used in organic synthesis were analyzed thoroughly in order to identify which reaction schemes occur. The analysis was restricted to reactions that shift electrons in pairs, as either a bonding or a free electron pair. Thus, only polar or heteiolytic and concerted reactions were considered. However, it must be emphasized that the reaction schemes list only the overall change in the distribution of bonds and ftee electron pairs, and make no specific statements on a reaction mechanism. Thus, reactions that proceed mechanistically through homolysis might be included in the overall reaction scheme. 

The decomposition of the peroxyketals (53) follows a stepwise, rather than a concerted mechanism. Initial homolysis of one of the 0-0 bonds gives an aikoxy radical and an a-peroxyalkoxy radical (Scheme 3.36).306"08"210 This latter species decomposes by P-scission with loss of either a peroxy radical to form a ketone as byproduct or an alkyl radical to form a peroxyester intermediate. The peroxyester formed may also decompose to radicals under the reaction conditions. Thus, four radicals may be derived from the one initiator molecule. 

The field of reduction is much less well charted than that of oxidation but a substantial literature exists nonetheless and is growing rapidly. Reductions are conveniently classified into (/) those involving and initial electron acceptance by the substrate (possibly followed by rapid protonation) and ( ) those involving electron acceptance concerted with, or followed very rapidly by, homolysis of the substrate the latter includes the important Fenton and silver-persulphate reactions, as well as reductions of halogens, hydrazine and possibly NO3 and NOJ. 

The mode of fission of some azo compounds into alkyl radicals and nitrogen has been studied by Pryor and Smith<8) using the following postulates (1) A molecule that decomposes by a concerted scission of both C—N bonds will not undergo cage return and will have a rate constant independent of viscosity (2) a molecule that decomposes by a stepwise scission of the C—N bonds can undergo cage recombination and the rate constant for decomposition will decrease with solvent viscosity increase provided that the lifetime of the radicals produced by the initial homolysis is of the same order... 

Saczewski and Debowski reported the l,4-diaza-3-oxa-Cope rearrangement of N-cyanate anilides (equation 52). Prototropic rearomatization of 176 and internal nucleophilic addition afford the corresponding benzimidazolinone 177, usually in moderate yields (32-78%). A concerted [3,3]-sigmatropic rearrangement is proposed based on the absence of para rearrangement product that usually results from homolysis or heterolysis of the N—O bond followed by recombination of the two radicals or ions. 

The homolysis of AIBN occurs in a concerted process with simultaneous breakage of the two C— N bonds to yield nitrogen and 2-cyano-2-propyl radicals. Reaction of the radicals with each other can occur in two ways to yield tetramethylsuccinodinitrile and dimethyl-A-(2-cyano-2-isopropyl)ketenimine ... 

In marked contrast to the generally accepted mechanism, the involvement of a radical pair produced by an alkene-induced 0—0 bond homolysis was suggested by Minisci and coworkers . In a combined experimental and theoretical study Curci, Houk and coworkers sought to differentiate between a radical pathway and the commonly accepted concerted mechanism. Both product and kinetic smdies tended to exclude a radical pathway. Computational studies at the B3LYP/6-31G level on the epoxidation of isobutylene with DMDO predicted an activation energy = 15.3 kcalmor ) significantly lower... 

One mechanistic matter that has caused quite a bit of general consternation about a decade ago concerns the experimental evidence for the involvement of diradical intermediates (proposed as sources for the observed radical products) in dioxirane epoxidations, which were thought to be formed through induced peroxide-bond homolysis by the alkene. Nonetheless, rigorous experimental and high-level theoretical work disposed such radical chemistry in the epoxidation of alkenic substrates. The latter computations unequivocally confirm the established concerted mechanism, in which both CO single bonds in the incipient epoxide are concurrently formed by way of an asynchronous, spiro-structured transition state for the oxygen transfer. 

These results, as well as rate studies " and kinetic isotope effects ", support a concerted, 5ptra-structured oxenoid-type transition state for the CH oxidations". The original oxygen-rebound mechanism has been discounted (see the computational work in Section I.D). Recently, however, the stepwise radical mechanism was revived in terms of the so-called molecule-induced homolysis , but such radical-type reactivity was severely criticized on the basis of experimental" and theoretical grounds. 

This is very common especially for dt species. A 16-electron species may add H2 directly, but an 18-electron species must lose a ligand first. A concerted H2 homolysis is often invoked, perhaps from... 

When the decomposition in question involves more than one bond in a concerted homolysis, as in an azoalkane (Equation 9.39), the disappearance of substrate is unaffected by recombination, but the number of R radicals available in the bulk solution to initiate other processes is less than two for each molecule of initiator consumed. Most experimental efforts to determine amount of cage recombination in these instances are of either the crossover or the scavenger type. In a crossover experiment, one decomposes a mixture of R—N=N—R and R —N=N—R geminate recombination must yield only R—R and R —R, whereas the separated radicals will recombine randomly to a statistical mixture of R—R, R —R, and R—R. 101... 

Initiation normally requires molecules with weak bonds to undergo homolytic cleavage to produce free radicals. Since bond homolysis even of weak bonds is endothermic, energy in the form of heat (A) or light (hv) is usually required in die initiation phase. However, some type of initiation is required to get any free-radical reaction to proceed. That is, you must first produce free radicals from closed-shell molecules in order to get free-radical reactions to occur. Benzoyl peroxide contains a weak 0-0 bond that undergoes thermal cleavage and decarboxylation (probably a concerted process) to produce phenyl radicals which can initiate free-radical chain reactions. 

A concerted, spiro-structured, oxenoid-type transition state has been proposed for C-H oxidation by dioxiranes (Scheme 5). This mechanism is based mainly on the stereoselective retention of configuration at the oxidized C-H bond [20-22], but also kinetic studies [29], kinetic isotopic effects [24], and high-level computational work support the spiro-configured transition structure [30-32], The originally proposed oxygen-rebound mechanism [24, 33] was recently revived in the form of so-called molecule-induced homolysis [34, 35] however, such a radical-type process has been experimentally [36] and theoretically [30] rigorously discounted. 

Concerted bimolecular reactions, such as H2-transfer by donor molecules (24) or direct H2-addition (15), are often thermochemically plausible and may play a role in bond breaking by converting thermally stable structures into structures that may decompose by free radical reactions. For example, the following H2-transfer leads to a structure that may readily dissociate by bond homolysis or 3-bond scission. 

Isomerizations occurring from the appropriate vibrational levels of the singlet state could be concerted reactions involving a photochemically allowed, suprafacial 1,3-acyl migration with a transition state as represented by E below. Alternatively, homolysis could lead to a shfart-lived singlet biradical F which could rebond either... 

In summary, most nitrenes exhibit some chemoselectivity in their intermolecular C—insertion reactions, with the order of reactivity being tertiary > secondary > primary C—bonds. Hence the ease of homolysis of the C—H bond in question would appear to be a good guide to its reactivity towards nitrene insertion, despite the fact that the reaction almost certainly involves a concerted reaction of the singlet nitrene and not a radical process. 

FIGURE 16. Concerted and kinetically coupled mechanisms for CooC bond homolysis and hydrogen atom abstraction, illustrated for the reaction catalyzed by glutamate mutase. Either mechanism could give rise to the deuterium isotope effects observed in pre-steady state stopped flow experiments. 

As discussed above, homolysis of AdoCbl and hydrogen abstraction from the substrate to form a substrate radical appear to be closely coupled or concerted reactions. This leaves isomerisation of the substrate radical to... 

---