Radical reactions selectivity

The purpose of this chapter is to provide an introduction to the scope and limitations of radical cyclization reactions. Emphasis will be placed on the reactivity profile of radicals with respect to chemo-, regio-and stereo-selectivity. Because most sequential radical reactions include at least one cyclization, they are also presented in this chapter. The organization of this chapter is similar to the previous chapter on radical additions. However, the basic principles of radical reactions, selectivity requirements, methods to conduct radical reactions (including experimental techniques), and mechanisms are extensively discussed in the previous chapter, and these aspects will be reiterated rather sparingly. A reader who is not familiar with the principles of radical reactions as applied to synthesis should read the addition chapter (Chapter 4.1, this volume) first. 

In many instances, reaction rates are limited by diffusion in the liquid phase. The rate of these reactions can be increased if the reaction is carried out in the supercritical phase. Typical examples are enzyme-catalyzed reactions as well as very fast reactions such as some free radical reactions. Selectivity considerations usually dominate in complex reactions. If some steps of the complex reaction are controlled by diffusion, changing the diffusivity changes relative rates of the reaction steps and affects the selectivity. 

High Peroxide Process. An alternative to maximizing selectivity to KA in the cyclohexane oxidation step is a process which seeks to maximize cyclohexyUiydroperoxide, also called P or CHHP. This peroxide is one of the first intermediates produced in the oxidation of cyclohexane. It is produced when a cyclohexyl radical reacts with an oxygen molecule (78) to form the cyclohexyUiydroperoxy radical. This radical can extract a hydrogen atom from a cyclohexane molecule, to produce CHHP and another cyclohexyl radical, which extends the free-radical reaction chain. 

Despite some recent discoveries, free radical reactions are still very much less common in azole chemistry than those involving electrophilic or nucleophilic reagents. In some reactions involving free radicals, substituents have little orienting effect however, rather selective radical reactions are now known. 

The enhanced selectivity of alkane bromination over chlorination can be explained by turning once again to the Hammond postulate. In comparing the abstractions of an alkane hydrogen by Cl- and Br- radicals, reaction with Br- is less exergonic. As a result, the transition state for bromination resembles the alkyl radical more closely than does the transition state for chlorination, and the stability of that radical is therefore more important for bromination than for chlorination. 

Until the early 1970s, the absence of suitable techniques for probing the detailed microstructure of polymers or for examining the selectivity and rates of radical reactions prevented the traditional view front being seriously questioned. In more recent times, it has been established that radical reactions, more often than not, are under kinetic rather than thermodynamic control and the preponderance of... 

Until the early 1970s, views of radical reactions were dominated by two seemingly contradictory beliefs (a) that radical reactions, in that they involve highly reactive species, should not be expected to show any particular selectivity,... 

Even though the rate of radical-radical reaction is determined by diffusion, this docs not mean there is no selectivity in the termination step. As with small radicals (Section 2.5), self-reaction may occur by combination or disproportionation. In some cases, there are multiple pathways for combination and disproportionation. Combination involves the coupling of two radicals (Scheme 5.1). The resulting polymer chain has a molecular weight equal to the sum of the molecular weights of the reactant species. If all chains are formed from initiator-derived radicals, then the combination product will have two initiator-derived ends. Disproportionation involves the transfer of a P-hydrogen from one propagating radical to the other. This results in the formation of two polymer molecules. Both chains have one initiator-derived end. One chain has an unsaturated end, the other has a saturated end (Scheme 5.1). 

Stable radicals can show selectivity for particular radicals. For example, nitroxides do not trap oxygcn-ecntcrcd radicals yet react with carbon-ccntcrcd radicals by coupling at or near diffusion controlled rates.179,184 This capability was utilized by Rizzardo and Solomon181 to develop a technique for characterizing radical reactions and has been extensively used in the examination of initiation of radical polymerization (Section 3.5.2.4). In contrast DPPH, w hile an efficient... 

The ends of polymer chains are often not representative of the overall chain composition. This arises because the initiator and transfer agent-derived radicals can show a high degree of selectivity for reaction with a particular monomer type (Section 3.4). Similarly, there is specificity in chain tennination. Transfer agents show a marked preference for particular propagating species (Section 6.2.2 and 6.2.3). The kinetics of copolymerization are such that the probability for termination of a given chain by radical-radical reaction also has a marked dependence on the nature of the last added units (Section 7.4.3). 

The N,0- and N,S-heterocyclic fused ring products 47 were also synthesized under radical chain conditions (Reaction 53). Ketene acetals 46 readily underwent stereocontrolled aryl radical cyclizations on treatment with (TMSlsSiH under standard conditions to afford the central six-membered rings.The tertiary N,0- and N,S-radicals formed on aryl radical reaction at the ketene-N,X(X = O, S)-acetal double bond appear to have reasonable stability. The stereoselectivity in hydrogen abstractions by these intermediate radicals from (TMSlsSiH was investigated and found to provide higher selectivities than BusSnH. 

This paper reviews the recent studies in the field of radical reactions of organobromine compounds. A special attention is paid to the use of metal-complex systems based on iron pentacarbonyl as catalysts this makes it possible to perform the initiation and chain transfer reactions selectively at C-Br bond. 

The use of metal-complex initiating systems proved to be especially promising in carrying out the reactions with acrylic monomers which can be easily polymerized, when the common initiators of radical reactions are excepted. The use of Fe(CO)s -I- DMFA system allows us to perform homolytical addition of bromoform to acrylic monomers selectively at C-Br bond with no essential polymerization (ref. 10). 

Methylene bromide is essentially less effective in radical reactions as a chain transfer agent as a result, the reactions with methylene bromide proceed non-selectively and with small conversion of starting substrate. 

Fischer H (2001) The persistent radical effect a principle for selective radical reactions and living radical polymerizations. Chem Rev 101 3581-3610... 

In the context of diagenesis in recent anoxic sediments, reduced carotenoids, steroids, and hopanoids have been identified, and it has been suggested that reduction by sulhde, produced for example, by the reduction of sulfate could play an important part (Hebting et al. 2006). The partial reduction of carotenoids by sulfide has been observed as a result of the addition of sulfide to selected allylic double bonds, followed by reductive desulfurization. This is supported by the finding that the thiol in allylic thiols could be reductively removed by sulhde to produce unsaturated products from free-radical reactions (Hebting et al. 2003). 

The reaction of P-H bonds with unsaturated substrates often proceeds without a metal catalyst [2]. In addition, add or base-catalyzed [3] as well as radical reactions [4] have been reported and extensively reviewed. Metal-catalyzed transformations like the ones described here, however, often offer improvements in rate, selectivity,... 

Adams, G.E. and Redpath, J.L. (1974). Selective free-radical reactions with proteins and enzymes pulse radiolysis and inactivation studies on papain. Int. J. Badiat. Biol. 25, 129-136. 

The fundamental mechanisms of free radical reactions were considered in Chapter 11 of Part A. Several mechanistic issues are crucial in development of free radical reactions for synthetic applications.285 Free radical reactions are usually chain processes, and the lifetimes of the intermediate radicals are very short. To meet the synthetic requirements of high selectivity and efficiency, all steps in a desired sequence must be fast in comparison with competing reactions. Owing to the requirement that all the steps be fast, only steps that are exothermic or very slightly endothermic can participate in chain processes. Comparison between addition of a radical to a carbon-carbon double bond and addition to a carbonyl group can illustrate this point. 

There is a good deal of information available about the absolute rates of free radical reactions. A selection from these data is given in Table 11.3 of Part A. If the steps in a projected reaction sequence correspond to reactions for which absolute rates are known, this information can allow evaluation of the kinetic feasibility of the reaction sequence. 

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