Carbanions SrnI reactions

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... 

Carbanions derived from side chain tertiary amides have also been cyclized to provide isoquinolones and isoindoles (equation 36).125 126 While benzyne intermediacy in the formation of the former is likely, the latter seems to arise through a SrnI reaction pathway. Synthesis of indole from the meta bromo compound (87), on the other hand, clearly involves an aryne cyclization. 27 A more versatile route to indoles is based on intramolecular addition of aminyl anions to arynes (equation 38).128 A somewhat similar dihydroindole preparation constitutes the first step in a synthesis of lycoranes (equation 39).129 The synthesis of (88) also falls in the same category of reactions, but it is noteworthy because only a few examples of ring closure of heteroarynes are mentioned in literature.27 28... 

Photostimulated SrnI reactions of carbanion nucleophiles in DMSO have been used to advantage in C—C bond formation (Scheme 1).25-27 Thus, good yields of substitution products have been obtained from neopentyl iodide on reaction with enolates of acetophenone and anthrone, but not with the conjugate base of acetone or nitromethane (unless used in conjunction, whereby the former acts as an entrainment agent).25 1,3-Diiodoadamantane forms an intermediate 1-iodo monosubstitution product on reaction with potassium enolates of acetophenone and pinacolone and with the anion of nitromethane subsequent fragmentation of the intermediate gives derivatives of 7-methylidenebicyclo[3.3.1]nonene. Reactions of 1,3-dibromo- and 1-bromo-3-chloro-adamantane are less effective.26... 

Bromopyridine undergoes photoassisted SrnI reaction with a variety of stabilized carbanions <1997JOC6152>. The reaction is carried out in the presence of potassium amide in liquid ammonia at —33 °C under photoirradiation at 350 nm and proceeds in moderate to good yield with anions derived from 2-benzyl-4,4-dimethyloxazoline, 2,4-dialkylthiazoles, and dimethyl methylphosphonate and also with carboxamide and ester enolates. 

Direct C-G bond formation at the 2-position of imidazole and benzimidazole was reported when imidazole was deprotonated with potassium /-butoxide in liquid ammonia via electrochemically induced SrnI. Coupling products 340 and 341 were isolated in a 4 1 ratio when the reaction started from 4-methylimidazole 338. Only one product 343 was obtained when 2-methylimidazole was used. It was proposed that delocalization of the negative charge of 345 resulted in some carbanion character (resonance contributors 346-348), and thus subsequent SrnI reaction with an electron deficient aryl chloride at carbon (Scheme 81) <1995JOC8015>. 

Various carbon- and heteroatom-centered nucleophiles have been successfully used in the SrnI arylation. Hence, carbanions readily obtained by deprotonation can be employed as nucleophiles. The reaction with phenolates leads to the formation of carbon-carbon bonds (ortho-arylation) [5], while aryl-heteroatom bond formation occurs when using Sn, P, As, Sb, S, Se and Te-centered anions. SrnI reactions are not sensitive to steric hindrance, and good yields are usually obtained for ortho-substituted aryl radicals [6]. Many functional groups such as OR, SAr, CF3, NH2, SO2R and CN are tolerated however, the niho group as aryl substituent leads to chain termination [7]. 

The reactivities of the substrate and the nucleophilic reagent change vyhen fluorine atoms are introduced into their structures This perturbation becomes more impor tant when the number of atoms of this element increases A striking example is the reactivity of alkyl halides S l and mechanisms operate when few fluorine atoms are incorporated in the aliphatic chain, but perfluoroalkyl halides are usually resistant to these classical processes However, formal substitution at carbon can arise from other mecharasms For example nucleophilic attack at chlorine, bromine, or iodine (halogenophilic reaction, occurring either by a direct electron-pair transfer or by two successive one-electron transfers) gives carbanions These intermediates can then decompose to carbenes or olefins, which react further (see equations 15 and 47) Single-electron transfer (SET) from the nucleophile to the halide can produce intermediate radicals that react by an SrnI process (see equation 57) When these chain mechanisms can occur, they allow reactions that were previously unknown Perfluoroalkylation, which used to be very rare, can now be accomplished by new methods (see for example equations 48-56, 65-70, 79, 107-108, 110, 113-135, 138-141, and 145-146)... 

Photo-stimulated reactions of neopentyl iodide with several carbanionic nucleophiles have been studied in which inhibition experiments with the TEMPO radical trap suggest the reaction occurs via an SrnI mechanism.76 Comparison of 22 nucleophiles in then. Srn 1 reactions with iodobenzene by Fe(II)- and photo-induction has revealed that both are enhanced by high electron-donation ability of the nucleophile. The radical anion Phl is a key intermediate.77 The SET reactions of perfluoroalkyl iodides have been reviewed.78 Flash photolysis of H2O2 was used to generate HO and 0 radicals which were reacted with a, a. z-trifluorotolucnc (TFT) and 4-fluorotoluene (4FT) and the rate constants calculated.79 The diminished reactivity of TFT towards HO or O with respect to toluene or benzene was consistent with radical addition to the aromatic ring, whilst the reactivity of 4FT was of the same order as electron-deficient toluenes, which favour H abstraction from the aliphatic side-chain. 

The photolysis of aromatic species with tetranitromethane in perfluoro alcohol solvent has been studied, in which the radical cations were observed by EPR spectroscopy.284 Photo-stimulated reaction of 1- and 2-haloadamantanes and 1,2- and 1,3-dihaloadamantanes with various carbanionic nucleophiles afforded products rationalized through an SrnI mechanism.285 286 Photolysis of the cycloadduct formed between a functionalized derivative of C6o and diazomethane has been shown to afford a pah of ling-opened structures (125) and (126) via a proposed biradical intermediate (127) (Scheme 19). The UV-photolytic fragments of /-butyl iodide (T and /-Bu ) have been ionized by resonance-enhanced multiphoton ionization for TOF mass spectro-metric analysis.287 A two-dimensional position-sensitive detector provided angular distribution and translational energy data. 

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... 

SET-induced chain reactions are usually much faster than Sn2 reactions, and if both pathways are accessible for a given pair of starting materials, products resulting from SrnI will usually predominate. This is, for example, observed for the first reaction sketched in Scheme4.4 [11, 16]. Electrochemical or zinc-mediated [17] reduction of the starting pyridinium salt yields a carbanion which, on reaction with Me2tBuS+, can either be methylated via Sn2 or tert-butylated via SrnI. Because the nucleophile... 

Reaction of o-iodoaniline 84 with carbanions under irradiation produced several 2-substituted indoles 85, or various fused indolic systems in moderate yields. The events leading to this outcome featured a C-C bond formation via the SrnI mechanism <03JOC2807>. 

Coupling of a carbanion with a free radical can also form a carbon-carbon bond. The overall result is substitution of some leaving group by a nucleophile, but the process can take place as a chain reaction (SrnI) involving radical-anion intermediates. Intermolecular radical-carbanion coupling is ex-... 

The SET mechanism is chiefly found, where X = 1 or NO2 (see 10-67). A closely related mechanism, the Sr I, takes place with aromatic substrates (Chapter 13). In that mechanism, the initial attack is by an electron donor, rather than a nucleophile. The SrnI mechanism has also been invoked for reactions of enolate anions with 2-iodobicyclo[4.1.0]heptane. An example is the reaction of 1-iodobicy-clo[2.2.1]heptane (20) with NaSnMe3 or LiPPh2, and some other nucleophiles, to give the substimtion product. Another is the reaction of bromo 4-bromoacetophe-none (21) with Bu4NBr in cumene. The two mechanisms, Sn2 versus SET, have been compared and contrasted." " There are also reactions where it is reported that radical, carbanion, and carbene pathways occur simultaneously.""... 

Phenylation of carbanions derived from olefins such as 1,3-pentadiene and l-(p-anisyl) propene and aromatics such as indene and fluorene are possible by the SrnI route in ammonia solvent. From the 1,3-pentadiene a mixture of mono-olefins and dienes is produced along with a small amount of di- and triphenylated material. Hydrogenation of the mixture gives 1-phenylpentane in 74% yield.106) Phenylation of 2- and 4-picolyl anions is conveniently effected in ammonia. When bromo- or iodobenzene is used for this purpose, reaction probably occurs by both SrnI and benzyne routes.111)... 

Reactions of 2-iodo- and 1,2-dihalo-adamantanes with carbanions in DMSO by the SrnI mechanism have been investigated, photo-stimulation or the presence of Fe(ll) bromide usually being necessary. Numerous experiments are described, e.g. 2-iodoadamantane (10) did not react with the enolate of acetophenone (11) in the dark, but under irradiation or in the presence of Fe(II) bromide gave the product (12) in yields of 62 and 88%, respectively. The photo-stimulated reaction was inhibited by p-dinitrobenzene, a good electron acceptor, a result in accord with an 5 rnI mechanism. 

The Photostimulated SrnI Process Reaction of Haloarenes with Carbanions... 

The photoinitiated reactions of 2-bromobenzonitrile and 2-bromo-3-cyano-pyridine with the carbanion of ethyl cyanoacetate afford the substitution product in good yields (90 and 80%, respectively) by an SrnI process. On the other hand, a non-chain radical nucleophilic mechanism is proposed to occur in the almost quantitative substitution of o-Cl, o-Br, and P-O2NQH4X (F, Cl, Br, I) with this anion in... 

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