Alkyl radical addition

This synthesis is only one example of a wide range of reactions which involve aryl (or alkyl) radical addition to electron-deficient double bonds resulting in reduction.The corresponding oxidative reaction using aryl radicals is the well known Meerwein reaction, which uses copper(II) salts. 

Alkyl radical addition reactions to styrene chromium tricarbonyl can be accomplished using alkyl halides (10 equiv) and (TMSlsSiH (5 equiv) in the presence of AIBN in refluxing benzene, for 18 h (Reaction 66). " These reactions are believed to proceed through intermediates in which the unpaired electron is interacting with the adjacent arene chromium tricarbonyl moiety since the analogous reaction with styrene affords only traces of addition products. 

Iron(II) salts, usually in conjunction with catalytic amounts of copper(II) compounds, have also been used to mediate radical additions to dienes91,92. Radicals are initially generated in these cases by reductive cleavage of peroxyesters of hydroperoxides to yield, after rearrangement, alkyl radicals. Addition to dienes is then followed by oxidation of the allyl radical and trapping by solvent. Hydroperoxide 67, for example, is reduced by ferrous sulfate to acyclic radical 68, which adds to butadiene to form adduct radical 69. Oxidation of 69 by copper(H) and reaction of the resulting allyl cation 70 with methanol yield product 71 in 61% yield (equation 29). 

The use of Et3B as a radical initiator makes it possible to carry out the addition of other alkyl radicals to nitrone (286) using alkyl iodides. Good yields have been obtained of products (288b-d) when an excess of the appropriate alkyl iodide was used (Scheme 2.110). It has been established that the yield of alkyl by-products (288a) tends to decrease with the increase of the reaction temperature. The stereochemical features of this reaction are explained by the alkyl radical addition taking place predominantly from the less hindered re-face of (286) to avoid steric interaction with the phenyl group (525). 

Excellent diastereoselectivity of alkyl radical addition was also observed in a number of other nitrones (291-293) (Scheme 2.111) (526). 

The tri-t-butylnitrosobenzene, TNB, is monomeric even in the solid state, but the principal advantage of this scavenger, exemplified in the mechanistic studies described in Section 3 (p. 47), is that it functions as an ambident spin trap (Terabe and Konaka, 1973). Thus, primary alkyl radicals add to form nitroxides in the normal way, but with t-alkyl radicals, addition occurs at oxygen, alkoxyaminyl radicals (ArNOR) being formed. Secondary alkyl radicals give mixtures of both species (Fig. 5). The alkoxyaminyl radicals have a lower g-value than the nitroxides (ca. 2.004 vs. 2.006) and their spectra are therefore centred at slightly higher field positions than those of the nitroxides. 

Cobalamin catalysed reduction of alkyl halides has found use in organic synthesis because, like square planar Ni(o), it allows formation of alkyl radicals in the bulk of the solution away from the electi ode surface. Alkyl radical addition to activated alkenes is achieved in high yields. In the cases of primary alkyl halides,... 

Additions of perfluoroalkyl groups generated from perfluoroalkyl iodides (Rpl) and perfluoroacyl peroxides [RpC(0)00(0)CRp] have also been carried out [50]. Another usable source of CEj radicals is the stable [(CF3)2CF]2 CCF2CE3 radical (Scheme 6.8) [51]. As with alkyl radical additions, ESR spectroscopic investigations... 

It should be noted that titanocene-catalyzed carbosilylation of alkenes and dienes, which uses alkyl halides and chlorosilanes, involves alkyl radical addition to styrenes and dienes [68]. The reaction uses butylmagnesiumchloride and a catalytic amount of titanocene dichloride, which would form the complex... 

Such relative lack of kinetic impact of olefinic fluorine substituents on alkyl radical addition reactions is consistent with Tedder s early studies on methyl affinities, the results of which are shown in Table 16, where the range of reactivities observed for the addition of methyl radical to ethylenes with varying fluorine content is seen to be relatively small [93,163],... 

One feature of the correlations is the scatter in the points for unsubstituted alkyl radicals, and this is particularly serious for the reaction of methyl radicals with ethylene. The experimental A-factor of this process is probably the most accurately known of any radical addition, and AS°9S is also very well established yet the point lies well away from the line through the other data. A possible explanation may be that in methyl radical, and other nucleophilic alkyl radical additions, the transition state is more like the reactants, so that the correlation with /15°98, a quantity calculated from product properties, is less likely. The early nature of the transition state in methyl radical reactions is... 

In the presence of an alkyl iodide, selective alkyl radical addition to the C-atom of the imine generated in situ occurs, overcoming the competitive phenylation reaction (Equation 14.20) [30]. The Ph- radical, generated by decomposition of the diazonium salt, as described before, generates the alkyl radical by selective iodine atom transfer (Equation 14.21). 

Intermolecular alkyl radical addition to imino compound can be also carried out as shown in eq. 4.12 with RI/Bu3SnH/Et3B system or Rl/In (indium) system. Here indium is used as an electron transfer agent to RI [31-33]. 

Highly diastereoselective alkyl radical addition to Oppolzer s camphorsultam derivative (33) of oxime provides enantiomerically pure a-alkyl-a-amino acid derivative (34) at — 78 °C by the same method as shown in eq. 10.16. Moreover, enantioselective tandem radical 1,2-difunctionalization of cinnamamide (35) can be carried out with high stereoselectivity, using the chelation manner of the cinnamamide and a chiral bisoxazoline ligand on Mgl2, as shown in eq. 10.17. 

When pyrrole 987 was subjected to the usual reaction conditions, l-(2,3-dihydro-17/-pyrrolizin-5-yl)-l-ethanone 988 was obtained as the major product. The desired diketone 989 was isolated in very low yield together with a small amount of the unexpected sulfone 984 (Equation 234). This compound is formed by alkyl radical addition at C-5, and subsequent aromatization by the loss of an acetyl radical. When pyrrole 987 was reacted with BusSnH/AIBN in the absence of CO, dihydropyrrolizines 988 and 984 were isolated in 74% and 23% yields, respectively <2000TL3035>. 

Kinetic data for the 5-exo cyclization of alkyl radical additions to the yV-aziridinylimino groups were obtained by competitive 5-exo cyclization to the A-aziridinylimino group versus an alkenyl group (Eq. 15). Reaction of compound 59 with BujSnH in benzene at 20 °C at 350 nm yielded only 61. Apparently, the primary alkyl radical... 

Figure 5. Kinetic data for alkyl radical additions to C=N bonds.

Furthermore, we also performed kinetic studies for alkyl radical additions onto different types of C=N bonds such as imines and oxime ethers. The kinetic data are summarized in Figure S. Kinetic analysis of the intramolecular addition of alkyl radicals to C=N bonds provides several experimentally important results. First, alkyl radical additions to C=N bonds are much faster than the corresponding additions to C=C bonds, indicating that C=N bonds are much better radical acceptors than C=C bonds. Furthermore, 5-exo cyclization is faster than 6-exo cyclization. Second, the intramolecular additions of alkyl radicals to C=N bonds are essentially irreversible. Third, alkyl radical additions to oxime ethers and hydrazones are faster than alkyl radical additions to imines, suggesting the possibility of a dependence of the cyclization rate on the electron density at the carbon atom of the radical acceptor. 

Scheme 22 Alkyl radical additions to phenylsulfonyl oxime ethers by Kim and Kim [ 14]...

Scheme 24 Alkyl radical addition to oxime ethers by Naito [15,16]...

Scheme 29 Alkyl radical additions to tetrafluorophenol-linked acrylate by Caddick [19]...

Scheme 46 Alkyl radical addition-cyclization by Naito [16,32]...

Scheme 7.6 Alkyl radical addition to glyoxylic oxime initiated by Et3B and proposed mechanism.

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