SrnI reaction mechanism

This is called the SrnI mechanism," and many other examples are known (see 13-3, 13-4,13-6,13-12). The lUPAC designation is T+Dn+An." Note that the last step of the mechanism produces ArT radical ions, so the process is a chain mechanism (see p. 895)." An electron donor is required to initiate the reaction. In the case above it was solvated electrons from KNH2 in NH3. Evidence was that the addition of potassium metal (a good producer of solvated electrons in ammonia) completely suppressed the cine substitution. Further evidence for the SrnI mechanism was that addition of radical scavengers (which would suppress a free-radical mechanism) led to 8 9 ratios much closer to 1.46 1. Numerous other observations of SrnI mechanisms that were stimulated by solvated electrons and inhibited by radical scavengers have also been recorded." Further evidence for the SrnI mechanism in the case above was that some 1,2,4-trimethylbenzene was found among the products. This could easily be formed by abstraction by Ar- of Ft from the solvent NH3. Besides initiation by solvated electrons," " SrnI reactions have been initiated photochemically," electrochemically," and even thermally." ... 

Furthermore, Saveant et al. have shown elegant examples of electrochemi-cally induced nucleophilic substitution of perfluoroalkyl halides. The reaction mechanism is a slightly modified version of the classical SRNI mechanism in... 

More complicated mechanisms of the same category are encountered in SrnI reactions (Section 2.5.6) where the electrocatalytic reaction, which corresponds to a zero-electron stoichiometry, is opposed to two-electron consuming side reactions (termination step in the chain process). 

Microelectrolytic techniques such as cyclic voltammetry are very well suited to observation of the electrochemical triggering of SrnI reactions and detailed investigation of their mechanism. A typical example of the evolution of the cyclic voltammetric responses of an Srn 1 substrate upon addition of increasing amounts of a nucleophile is shown in Figure 2.39. 

FIGURE 2.39. Example of the cyclic voltammetric observation of an SrnI reaction upon addition of the nucleophile. Upper scheme ECE-DISP reduction of the substrate in the absence of nucleophile. Lower scheme SrnI mechanism. 

Similarly, several examples of reactions of perliuoroalkyl halides have been demonstrated to follow an SrnI -type mechanism (Section 3, p. 75). Since, here too, dissociative electron transfer is likely under the conditions of the reactions [Section 2, pp. 54-56 (Andrieux et ai, 1990b)], the substitution process most probably also follows mechanism (134) rather than (103). The same is also likely to be true with alkyl mercurials (Russell, 1989). 

Unactivated aryl iodides undergo the conversion Arl — ArCHj when treated with tris(diethylamino)sulfonium difluorotrimethylsilicate and a palladium catalyst.131 A number of methods, all catalyzed by palladium complexes, have been used to prepare unsymmetrical biaryls (see also 3-16). In these methods, aryl bromides or iodides are coupled with aryl Grignard reagents,152 with arylboronic acids ArB(OH)2,153 with aryltin compounds Ar-SnR3,154 and with arylmercury compounds.155 Unsymmetrical binaphthyls were synthesized by photochemically stimulated reaction of naphthyl iodides with naphthoxide ions in an SrnI reaction.156 Grignard reagents also couple with aryl halides without a palladium catalyst, by the benzyne mechanism.157 OS VI, 916 65, 108 66, 67. 

Protic solvents (other than ammonia) are generally unsuitable on account of their high acidity relative to that of most nucleophiles used in SrnI reactions. Water was found to be unsuitable, even with water-soluble substrates and weakly basic nucleophiles.46 The reported reaction of halobenzenes with PhO in 50% aqueous Bu OH, catalyzed by sodium amlagam,51 was shown to be unreproducible.52 Methanol was used as solvent in an unusual reaction, believed to be occurring by the Srn 1 mechanism and catalyzed by MeO" at 147 °C, in which PhS replaces the bromine in 3-bromoisoquinoline.53 Other protic solvents have been reported to give acceptable yields in SrnI reactions, but on the whole these involve substrates which give good yields in other solvents as well. 

The solution of the riddle posed by Komblum s dark SrnI reaction is as follows. The nucleophile does work as a single electron-transfer initiator of the chain process. However, the mechanism of initiation does not consist of a mere outer-sphere electron transfer from the nucleophile to form the anion radical of the substrate. Rather, it involves a dissociative process in which electron transfer and bond breaking are connected (Costentin Saveant 2000). Scheme b at the beginning of Section 8.2 (p. 387) illustrates this mechanism. 

SrnI reactions with aryl halides were also observed. Their general mechanism is presented in Scheme 194b and illustrated in the subsection on SET reactions. 

Electron transfer is also the first step of the SrnI substitution mechanism (Chapter 2). In reactions that proceed by the SrnI mechanism, the electron donor is usually the nucleophile. The nucleophile may be photoexcited to give its electron more energy and make it more prone to transfer. 

There is good evidence that some nucleophilic substitution reactions do involve a single electron transfer, but the best established use a slightly different mechanism. These are the SrnI reactions, with the subscript RN standing for radical nucleophilic. Examples are the reaction of the nitronate anion 4.14 with p-nitrobenzyl chloride 4.15, 251 and the reaction of the pinacolone enolate 4.16 with bromobenzene.252 The former might have been a straightforward SN2 reaction, but actually takes the S l pathway because the nitro groups make the electron transfer exceptionally easy. The latter cannot take place by a conventional Sn2 reaction, because aryl (and vinyl) halides are not susceptible to direct displacement, and the S l pathway overcomes this difficulty. 

Some unusual organizational decisions have been made, too. SrnI reactions and carbene reactions are treated in the chapter on polar reactions under basic conditions. Most books on mechanism discuss SrnI reactions at the same time as other free-radical reactions, and carbenes are usually discussed at the same time as carbocations, to which they bear some similarities. I decided to place these reactions in the chapter on polar reactions under basic conditions because of the book s emphasis on teaching practical methods for drawing reaction mechanisms. Students cannot be expected to look at a reaction and know immediately that its mechanism involves an electron-deficient intermediate. Rather, the mech-... 

Subsequent research showed the SrnI mechanism to occur with many other aromatic compounds. The reaction was found to be initiated by solvated electrons, by electrochemical reduction, and by photoinitiated electron transferNot only I, but also Br, Cl, F, SCeHs, N(CH3)3, and 0P0(0CH2CH3)2 have been foimd to serve as electrofuges. In addition to amide ion, phosphanions, thiolate ions, benzeneselenolate ion (C HsSe"), ketone and ester enolate ions, as well as the conjugate bases of some other carbon acids, have been identified as nucleophiles. The SrnI reaction was observed with naphthalene, phenanthrene, and other polynuclear aromatic systems, and the presence of alkyl, alkoxy, phenyl, carboxylate, and benzoyl groups on the aromatic ring does not interfere with the reaction. ... 

Since the pioneering studies of Bunnett [3], the scope of the unimolecular radical nucleophilic substitution (SrnI) reaction has increased considerably, and today this approach is well established for the formation of aryl-carbon and aryl-heteroatom bonds. The SrnI reaction is a chain process which includes radicals and radical anions as intermediates the reaction mechanism is depicted in Scheme 13.1 [1]. 

Eq. 11.45 shows an example of an SrnI reaction. It does not seem to fit the criteria of either Sn2 or SnI. Substitution takes place on a tertiary center that has a very electron withdrawing group on it. The tertiary center impedes an Sn2 reaction, while the electron withdrawing group impedes an SnI reaction. In addition, the nucleophile seems too bulky for a standard Sn2 reaction. The SrnI mechanism allows otherwise unfavorable substitutions to occur. Even 1-adamantyl systems can undergo facile substitution, and the leaving groups can be NO2, N3, and sometimes even phenyl ... 

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