Free radical addition efficiency

A highly efficient synthesis of geminally substituted dicyanocyclopropanes has been achieved by Boldt and coworkers using a free radical addition of bromodicyanomethane to aliphatic and cyclic alkenes under photolytic reaction conditions (equation 65) . The intermediate addition products, i.e. 2-bromoalkylmalononitriles (224), are easily isolated and can be transformed info the dicyanocyclopropanes by treatment with... 

Generalized methods of initiating the polymerization of these monomers have recently been reviewed in detail [9], and were also mentioned briefly earlier in this Chapter. As with vinyl monomers initiation can be efficient and rapid, with the production of a fixed number of active centres. Propagation appears to be much slower, however, and rates of polymerization are comparable to those in free radical addition polymerizations. Techniques such as dilatometry, spectrophotometry etc. are therefore convenient for kinetic investigation of this type of cationic reaction. 

The reaction shown in Scheme 6.1 occurs most of the time via free-radical addition to electron-rich/electron-poor C=C double bonds (this mechanism will be discussed in more detail below). However, in the case of addition to an cc,(0-unsaturation (Scheme 6.2), the reaction needs mild base/nucleophilic catalysis, which is slightly less efficient than the radical-mediated mechanism because the C=C double bond is electron-deficient and must be activated [5]. 

The first synthesis of an (a-haloalkyl)boronic ester [8], a free radical addition of a tetrahalomethane, was followed by mechanistic studies that indicated the potential for stereospecific alkylation with Grignard reagents via borate intermediates [9], if only there had been a way to obtain asymmetric examples. The discovery of the efficient reaction of (dichloromethyl)lithium with boronic esters to form (a-chloroalkyl)boron-ic esters by insertion of a CHCl group into the B-C bond opened a new opportunity [10]. Boronic esters of pinanediol, prepared from (+)-a-pinene by osmium tetroxide catalyzed oxidation, were soon found to undergo the insertion reaction with a strong asymmetric bias, with diastereomeric selectivities frequently in the 90-95% range [llj. It was subsequently found that anhydrous zinc chloride promotes the reaction and increases diastereoselectivity to as high as 99.5% in some cases [12]. 

Lewis acid catalyzed enantioselective conjugate free-radical addition/trapping reactions represent an efficient approach to the formation of adjacent chiral centers. 

Unsymmetrical dialkyl peroxides are obtained by the reaction of alkyl hydroperoxides with a substrate, ie, R H, from which a hydrogen can be abstracted readily in the presence of certain cobalt, copper, or manganese salts (eq. 30). However, this process is not efficient since two moles of the hydroperoxide are consumed per mole of dialkyl peroxide produced. In addition, side reactions involving free radicals produce undesired by-products (44,66). 

In contrast, antioxidants can have an opposite effect when peroxide curing. Because peroxide cross-linking involves a free-radical mechanism, and antioxidants are designed to scavenge free radicals, it is obvious that peroxide efficiency can be compromised by the addition of antioxidants. Thus the decomposition products of the ppds were acting as accelerators (29). 

While free radical attack in step (i) is by no means confined to carbon atom 4, the products obtained in the reactions involving the lower polyisoprenes indicate that this process is the dominant one. Likewise in step (ii) sulfur may frequently add at carbon atom 4 rather than at atom 2. Addition in the manner shown is indicated, however, by infrared spectra, which reveal the formation of —CH=CH— groups during vulcanization. The scheme accounts also for the observed constancy of the C/H ratio during vulcanization and for the relatively low efficiency of utilization of sulfur in the formation of cross-linkages in the absence of accelerators. A preponderance of the sulfur is involved in addition without formation of cross-linkages a considerable fraction of the thus-combined sulfur may occur in five- and six-membered heterocyclic rings formed by the mechanisms indicated. 

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. 

The same group recently disclosed a related free radical process, namely an efficient one-pot sequence comprising a homolytic aromatic substitution followed by an ionic Homer-Wadsworth-Emmons olefination, for the production of a small library of a,/3-unsaturated oxindoles (Scheme 6.164) [311]. Suitable TEMPO-derived alkoxy-amine precursors were exposed to microwave irradiation in N,N-dimethylformam-ide for 2 min to generate an oxindole intermediate via a radical reaction pathway (intramolecular homolytic aromatic substitution). After the addition of potassium tert-butoxide base (1.2 equivalents) and a suitable aromatic aldehyde (10-20 equivalents), the mixture was further exposed to microwave irradiation at 180 °C for 6 min to provide the a,jS-unsaturated oxindoles in moderate to high overall yields. A number of related oxindoles were also prepared via the same one-pot radical/ionic pathway (Scheme 6.164). 

The crosslinking efficiency of many peroxide-initiated free radicals is low. These labile radicals can be converted to more stable radicals by contact in situ with polyfunctional monomers to form a three-dimensional network. Crosslinking efficiency is thus increased by some 20%. In addition, these materials act as plasticisers during processing and in some cases also act as hardening agents. 

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