Homolytic substitution reaction

An interesting method for the substitution of a hydrogen atom in rr-electron deficient heterocycles was reported some years ago, in the possibility of homolytic aromatic displacement (74AHC(16)123). The nucleophilic character of radicals and the important role of polar factors in this type of substitution are the essentials for a successful reaction with six-membered nitrogen heterocycles in general. No paper has yet been published describing homolytic substitution reactions of pteridines with nucleophilic radicals such as alkyl, carbamoyl, a-oxyalkyl and a-A-alkyl radicals or with amino radical cations. 

Homolytic substitution reactions including homolytic allylation, radical [2,3]-migrations and stereochemical reactions been reviewed. The review also highlights the possible applications of homolytic substitution reactions. ni reactions at silicon (by carbon-centred radicals in the a-position of stannylated silyl ethers) are efficient UMCT reactions producing cyclized alkoxysilanes. Bimolecular reactions can also be facilitated in good yield (Schemes 32 and 33). ... 

Homolytic Substitution Reactions of Heteroaromatic Compounds in Solution K. C. Bass and P. Nababsing, Adv. Free-Radical Chem., 1972, 4, 1-48. 

In homolytic substitution reactions, the 2-position of thiophene is the preferred site of attack. This is easily rationalized in terms of frontier orbital theory (B-76MI31401). Because of symmetry, both HOMO and LUMO of thiophene have the same absolute values for the coefficients (as shown in 216). Thus it is immaterial whether the [SOMO (radical)-HOMO (thiophene)] or the [SOMO (radical)-LUMO (thiophene)] interaction determines the site of attack only the 2-position is the point at which the radical would attack. The same conclusion is iso reached by consideration of product development control (74AHC(16)123). Attack at the 2-position would result in a transition state with an allylic radical, which would be stabilized to a greater extent than the one arising from attack at position 3 (Scheme 57). 

Redox and homolytic substitution reactions almost never directly form C—C, C—N and C—O bonds. Such bonds are generated in radical addition reactions (Scheme 14). Intermolecular addition reactions are presented in this chapter. Cyclization reactions have important similarities with, and differences from, bimolecular additions, and they are presented in Chapter 4.2 of this volume. Falling under the umbrella of addition reactions are radical eliminations (the reverse of addition) and radical migrations (which are usually, but not always, comprised of an addition and an elimination). 

Photolysis of PTOC imidate esters generated amidyl radicals which can undergo intramolecular homolytic substitution reactions (Scheme 29).152 The ratio of exo to endo products observed for die reaction of each of die diiocarbonylimidazolide diastereomers (70) and (71) with B113S11H was found to be different indicating tiiat die intermediate radical (72) produced in each case was generated and reacted in a different conformation, respectively (Scheme 30).153... 

FIGURE 65. Homolytic substitution reactions which were investigated in Reference 187. The calculated transition states are shown in Figure 66... 

FIGURE 66. Optimized transition states at MP2 for the homolytic substitution reaction of the CH3 substituent in HYCH3 (Y = S, Se, Te) by H3E (E = Si, Ge, Sn). Bond distances are in A, angles in deg. The calculated activation energies (kcalmol-1) at QCISD//MP2 refer to the forward reaction (AE ) and the reverse reaction (A 2 ), respectively (see Figure 65). Reprinted from Reference 187 with permission from Elsevier Science... 

On the other hand, it was shown more recently that radicals could be generated from suitable substrates 33 in the coordination sphere of a SET active metal complex. The metal changes its oxidation state in this process by one (Fig. lib). In such a coordinative chain reaction, the coordinated radical 33A is subject to the subsequent process. The product 34 is in this case released from radical 33B by a homolytic substitution reaction (Sni) with respect to the coordinated atom or group and by SET at the metal. 

Minisci s group developed homolytic substitution reactions of electron-poor arenes or hetarenes providing alkylarenes and -hetarenes extensively (see also Part 2, Sect. 2.5). The state of the art was reviewed thoroughly, so that the methodology is illustrated only by selected examples [435, 436, 437]. A protocol using silver nitrate as the catalyst and sodium peroxydisulfate as the stoichiometric oxidant proved to be very useful for the catalytic oxidative generation of radicals [438]. 

A detailed discussion on the properties of Mils is given in Section V.D.l and its calculated structure is shown in Figure 9. In this section we will discuss the role of pentacoordinated MRs in free-radical homolytic substitution reactions. 

The calculations predict that the degenerate homolytic substitution by silyl radical at the silicon atom of disilane proceeds by mechanisms that involve either a back-side or a front-side attack, having similar activation barriers of 12.6 and 13.9 kcalmol-1, respectively. Similar conclusions were obtained for the degenerate homolytic substitution reactions involving GeH3 and SnH3, with barriers of 15.6 kcalmol-1 ( back-side ) and... 

One of us, as well as Bottoni, recently investigated homolytic substitution reactions of silyl radicals at the halogen atom of halomethanes (CH3X, X = Cl, Br, I), and the chalcogen atom in methanechalcogenols (CH3EH, E = S, Se, Te) and alkyltellurols, with expulsion of alkyl radical (equations 12 and 13)40-43. 

Aromatic heterocycles may, of course, give rise to tr-radicals, e.g., 2-pyridyl (14). This review does not treat of these except incidentally where there is ambiguity as to whether a radical is a or n in character, or where a tr-radical occurs unexpectedly. Equally, transient radical adducts arising in homolytic substitution reactions which may contain a heteroaromatic moiety are not systematically considered. These have been discussed already in this Series.6... 

The homolytic substitution reactions of thiophene have been extensively surveyed in CHEC(1984) and CHEC-11(1996) <1984CHEC(4)741, 1996CHEC-II(2)491>. Not much work seems to have been done in this area since. 

In a thorough study on the homolytic substitution reaction at silicon, Studer and Steen reported a mild method for the formation of cyclic five-membered alkoxysilanes based on tandem intermolecular add-ition/intramolecular homolytic substitution [137], whereby the reaction of homoallylic stannylated silylether 149 with ethyl iodoacetate in the presence of (Me3Sn)2 led to the desired Sni product 150 in high yield as the sole trans diastereoisomer (Scheme 49). While the 1,2 induction proved to be very high, leading in some cases to a unique diastereoisomer, 1,3 stereoselectivities were... 

The reaction was initially believed to be a homolytic substitution reaction by ano-dically generated cyano radicals [214]. However, while significant oxidation of CN takes place at a potential as low as 0.5 V versus SCE, the cyanation process will occur only in the region around or above "1/2 of the substrate. This strongly implies a direct mechanism [215,219,220] analogous to that for acetoxylation. 

---