SRNI reactions

Although the nitro group plays a crucial role in most of these SrnI reactions, reactions of this type have synthetic application beyond the area of nitro compounds. The nitromethyl groups can be converted to other functional groups, including aldehydes and carboxylic acids.Nitro groups at tertiary positions can be reductively removed by reaction with the methanethiol anion.This reaction also appears to be of the electron-transfer type, with the methanethiolate anion acting as the electron donor ... 

The unique feature of the SrnI reactions of substituted alkyl nitro compounds is the facility with which carbon-carbon bonds between highly branched centers can be formed. This point is illustrated by several of the examples in Scheme 12.7. 

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." ... 

The ability of a nitro group in the substrate to bring about electron-transfer free radical chain nucleophilic substitution (SrnI) at a saturated carbon atom is well documented.39 Such electron transfer reactions are one of the characteristic features of nitro compounds. Komblum and Russell have established the SrnI reaction independently the details of the early history have been well reviewed by them.39 The reaction of p-nitrobenzyl chloride with a salt of nitroalkane is in sharp contrast to the general behavior of the alkylation of the carbanions derived from nitroalkanes here, carbon alkylation is predominant. The carbon alkylation process proceeds via a chain reaction involving anion radicals and free radicals, as shown in Eq. 5.24 and Scheme... 

Crozet and co-workers have used S l reactions for synthesis of new heterocycles, which are expected to be biologically active (see also Section 7.3, which discusses synthesis of alkenes). For example, 2-chloromethyl-5-nitroimidazole reacts with the anion of 2-nitropropane to give 2-isopropylidene-5-nitroimidazole. It is formed via C-alkylation of the nitronate ion followed by elimination of HN02 (Eq. 5.33).51a Other derivatives of nitroimidazoles are also good substrates for SrnI reactions.5113 0... 

Crozet and coworkers have used SrnI reactions followed by elimination of HN02 for the synthesis of various new heterocyclic compounds substituted with alkenyl groups. These compounds are expected to be important for pharmaceutical use (see Eq. 7.139).185... 

From the foregoing it can be seen that the nitro group can be activated for C C bond formation in various ways. Classically the nitro group facilitates the Henry reaction, Michael addition, and Diels-Alder reaction. Kornblum and Russell have introduced a new substitution reaction, which proceeds via a one electron-transfer process (SrnI). The SrnI reactions have recently been recognized as useful tools in organic synthesis. All these reactions can be used for the preparation of alkenes as described in this chapter. 

The chlorodifluoromethylated ketone 130 proved to be a valuable substrate for promoting SrnI subtitution reaction with sodium phenylthiolate and to generate a new a-(phenylthio)-a,a-difluoroacetophenone derivative 131 (Equation 57) <2001TL3459>. Upon treatment with nitronate anions under classical SrnI reaction conditions or MW irradiation, 6-chloromethyl-5-nitro-imidazo[2,l- ]thiazole 132 yielded 5-nitroimidazothiazoles bearing a trisubstituted ethylenic double bond at the 6-position (Equation 58) <2001SC1257>. 

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). 

As shown in Section 2.2.7, chemical reactions may be triggered by electrons or holes from an electrode as illustrated by SrnI substitutions (Section 2.5.6). Instead of involving the electrode directly, the reaction may be induced indirectly by means of redox catalysis, as illustrated in Scheme 2.15 for an SrnI reaction. An example is given in Figure 2.30, in which cyclic voltammetry allows one to follow the succession of events involved in this redox catalysis of an electrocatalytic process. In the absence of substrate (RX) and of nucleophile (Nu-), the redox catalysis, P, gives rise to a reversible response. A typical catalytic transformation of this wave is observed upon addition of RX, as discussed in Sections 2.2.6 and 2.3.1. The direct reduction wave of RX appears at more negative potentials, followed by the reversible wave of RH, which is the reduction product of RX (see Scheme 2.21). Upon addition of the nucleophile, the radical R is transformed into the anion radical of the substituted product, RNu -. RNu -... 

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. 

The SrnI reaction thus appears as a reaction in which single electron transfer plays a pre-eminent role but is by no means a single elementary step. A different problem is that of the possible involvement of single electron transfer in reactions that are not catalysed by electron injection (or removal). A typical example of such processes is another substitution reaction, namely. 

There are few examples of SrnI reactions leading to organometallic compounds. This does not seem to result from lack of reactivity but rather from a limited number of investigations. The reaction of secondary and... 

The question we address now is that of the possible role of single electron transfer in substitution reactions that, unlike SrnI reactions, are not catalysed by electron injection. The problem is twofold. One side of it consists in answering the questions do bond breaking and bond formation belong to two different and successive processes, i.e. (135) followedhy (136), or, more... 

The sulphur, selenium and tellurium nucleophiles required for these SrnI reactions can be generated in a preliminary step by reduction of a sacrificial cathode of graphite mixed with elemental sulphur, selenium or tellurium [160,162]. 

Aromatic substitution by the SrnI reaction, 54, 1 Arsinic acids, 2, 10 Arsonic acids, 2, 10... 

Photoirradiation of a mixture of the 1,3-dioxane (46) and triazole in acetonitrile containing potassium carbonate gave a mixture of the N(l) and N(4) derivatives (47a) and (47b) probably by an SrnI reaction (Equation (16)) <86TL6209>. 

JCS(P1)249>. In an interesting alternative to direct acylation of this heterocycle, Pierini and Rossi examined the photostimulated SrnI reaction of the enolate of 2-acetyl-1-methylpyrrole 36 with haloarenes (e.g., iodobenzene, 37) as well as neopentyl iodides to afford a-substituted acetyl pyrroles 38 <99JOC6487>. 

SrnI reactions have a fairly wide scope. There is no requirement for activating groups or strong bases. Alkyl, alkoxy, aryl, and COO groups do not interfere, although Me2N, O, and N02 groups do interfere. Cine substitution is not found. 

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. 

Although the SRNi reaction is of considerable utility in heterocyclic synthesis (80JOC1546, 80TL1943), its scope is restricted by the poor... 

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