SRN1 reactions mechanism

The base may deprotonate either C3 or C4. Deprotonation of C3 makes it nucleophilic. We need to form a new bond from C3 to C8 via substitution. The mechanism of this aromatic substitution reaction could be addition-elimination or Sr I. The requirement of light strongly suggests SRN1. See Chap. 2, section C.2, for the details of drawing an SRN1 reaction mechanism. 

The mechanistic aspects of the SRN1 reaction were discussed in Section 11.6 of Part A. The distinctive feature of the SRN1 mechanism is an electron transfer between the nucleophile and the aryl halide.181 The overall reaction is normally a chain process. 

The mechanism of the reaction depicted in Scheme 4-6 differs from the SN1 or SN2 mechanism in that it involves the stage of one-electron oxidation reduction. The impetus of this stage may be the easy detachment of the bromine anion followed by the formation of the fluorenyl radical. The latter is unsaturated at position 9, near three benzene rings that stabilize the radical center. The radical formed is intercepted by the phenylthio anion. That leads to the anion radical of the substitution product. Further electron exchange produces the substrate anion radical and the final product in its neutral state. The reaction takes place and consists of radical (R) nucleophilic (N) monomolecular (1) substitution (S), with the combined symbol of SRN1. Reactions of SrnI type may have both branch-chain and nonchain character. 

Several reviews have been published in relation to aromatic SRN1 reactions [6-9], and to the synthetic applications of the process [10,11]. In this chapter an introductory short survey of the general mechanistic aspects, the aromatic substrates and nucleophiles involved in the photoinduced SRN1 mechanism will be presented. The main emphasis being related to its synthetic capability, target applications and to the more recent advances in the field. 

Intramolecular examples of photostimulated SRN1 reactions implying excited anions with a demonstrated chain mechanism have been reported as in the case of anilide anions and JV-acyl benzylamines used as precursors of oxindoles and isoquinolines [129]. 

Perhaps the most common use of carbanions in organic photochemistry is in the synthetically useful SRN1 reaction. The reaction proceeds via a radical chain mechanism, which requires the transfer of an electron in an initiation step. Photoinduced electron transfer from a carbanion, which also serves as the nucleophile, is a convenient and mild method of initiation. A generalized mechanism is shown in Scheme 9. The excited state anion, with its enhanced... 

A different mechanism for the SRN1 reaction has been proposed in an attempt to unify conceptually the SN2, SRN1 and SN1 mechanisms (Shaik, 1985). As sketched in Scheme 14, one electron is transferred, thermally or... 

Several reports have appeared concerning photostimulated Srn1 reactions of aryl halides. In these processes substitution occurs via a chain mechanism as follows ... 

Substitution reactions by anions at carbon are also known to occur by initial electron transfer. The mechanism of such transformations was first characterized by Russell and Danen (14) and Kornblum et al. (15), and Bunnett (16) significantly developed its applications and named it the SRN1 reaction an... 

A potential advantage of the SRN1 mechanism is that it is not particularly sensitive to the nature of other aromatic ring substituents, although EWG substituents favor the nucleophilic addition step. For example, chloropyridines and chloroquinolines are excellent reactants.182 A variety of nucleophiles undergo the reaction, although not always in high yield. The nucleophiles that have been found to participate in... 

We may now ask the question What are the factors which govern whether the reaction between a nucleophile N and a substrate RX will take place by an Sn2 process or by an electron transfer mechanism in which radical species are generated The first step (89) in the SRN1 pathway exemplifies electron transfer. 

The procedure reported here is based on a reaction discovered by Bunnett and Creary, and was first employed for preparative purposes by Bunnett and Traber.3 It is attractive because of the high yield obtained, the ease of work-up, and the cleanliness of the reaction. The reaction is believed to occur by the SRN1 mechanism, which involves radical and radical anion intermediates.2,4 The SRN1 arylation of other nucleophiles, especially ketone enolate ions,5 ester enolate ions,6 picolyl anions,7 and arenethiolate ions,8 has potential application in synthesis. 

The preceding examples show the possibilities and also the present limitations of PTC. The conversion of the heterocycle to its /V-oxide or complex-ation of benzene with Cr(CO)3 promote reaction of unactivated compounds. But these approaches are based on a multistep procedure. A very promising new method is the one-step reaction of unactivated aryl (and heteroaryl) halides by way of the SRN1 mechanism developed by Bunnett.232,233 This has been applied to heterocyclic molecules mainly by Wolfe and Carver.234 A pyridine derivative serves as an example. 

Just as in phenyl halides, the halogen can be replaced by hydrogen, by a metal, or be coupled. Two of the four mechanisms of such nucleophilic substitutions are also familiar from benzene chemistry via arynes and by the SRN1 mechanism. However, of the two further mechanisms of nucleophilic replacement, the ANRORC is unique to heterocycles, and SAE reactions occur only with strongly activated benzenoid systems. 

Unactivated aryl halides also undergo nucleophilic displacement via electron transfer in the initial step the so-called SRN1 mechanism. It is now clear that in the case of heteroaromatic compounds, nucleophilic substitution by the Srn process often competes with the addition-elimination pathway. The SRN reactions are radical chain processes, and are usually photochemically promoted. For example, ketone (895) is formed by the SRN1 pathway from 2-chloroquinoxaline (894) (82JOC1036). 

Intramolecular nucleophilic substitution by the anions of o-haloanilides is another viable oxindole synthesis. This is a special example of the category Ic process described in Section 3.06.2.3. The reaction is photo-stimulated and the mechanism is believed to be of the electron-transfer type SRN1 rather than a classical addition-elimination mechanism. The reaction is effective when R = H if 2 equivalents of the base are used to generate the dianion (equation 202) (80JA3646). 

The reactions of 1,3-dihaloadamantanes with various carbanions in DMSO have been studied.18 For example, potassium enolates of acetophenone and pinacolone and the anion of nitromethane react with 1,3-diiodoadamantane (19) under photo-stimulation a free-radical chain process forms a 1-iodo monosubstitution product (20) as an intermediate, which undergoes concerted fragmentation to yield derivatives of 7-methylidenebicyclo[3.3.1]nonene (21). These and other results were interpreted in terms of the Srn1 mechanism. The work has been extended to the reactions of 1- and 2-halo- and 1,2-dichloro-adamantanes, examples of the SrnI mechanism again being found.19... 

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