SRN1 reaction initiation

A similar goal can be achieved using the conditions of the SRN1 reaction. The anion of DMSO is generated by NaNH2 in DMSO andtheSRNl reaction is initiated by sunlight402 (Scheme 6). 

Cleavage of a C—S bond in the initially formed anion radical has been shown to be the first chemical step in the electrochemically induced rearrangement of 5,5-diarylbenzene-1,2-dicarbothioates to 3,3-bis(arylthio)phthalides in dimethylformamide. The reaction can be effected with 0.1 F/mol and is considered a kind of internal SRN1 reaction (Praefke et al. 1980). 

SRN1 reactions are, in general, eased up sterically. This feature is employed for synthetic purposes. For instance, the cyanoacetate substituent was inserted in the sterically shielded position of a benzene ring (Suzuki et al. 1983) (Scheme 8-14). The reaction proceeds in hexamethylphosphorotriamide. Photoirradiation results in the formation of undesirable by-products, but initiation with cuprous iodide leads to the target substance, at more than 60% yield. 

Substituted 2,3-dihydro-l-H-indoles 26 are accessible by the versatile application of a 5-exo ring closure process during the propagation cycle in the SRN1 reaction [67]. Following the initial ET and fragmentation of the radical anion of the substrate, the... 

Argiiello, J.E., Penenory, A.B. and Rossi, R.A. (2000) Quantum yields of the initiation step and chain propagation turnovers in SRN1 reactions photostimulated reaction of l-iodo-2-methyl-2-phenyl propane with carbanions in DMSO. Journal of Organic Chemistry, 65, 7175-7182. 

Photochemical aromatic substitution initiated by a reductive step as in SRN1 reactions can be used for the synthesis of cephalotaxinone (15). The corresponding iodoketone precursor cyclizes in liquid ammonia under photolysis [15]. 

It is known that acetone enolate anion does not react with primary alkyl radicals, and that nitromethane anion is not capable of initiating the SRN1 reactions even under irradiation [99]. Thus, the photo stimulated reactions of 25 with nitromethane anion as nucleophile and acetone enolate anion as entrainment reagent (which enables SRN1 initiation but cannot compete with the coupling of the methylene radical with nitromethane anion after cyclization) render the cyclized products 26 (Sch. 25) [98]. 

The fragmentation of radical anions and the reverse reaction, the addition of anions to radicals, are the critical steps of SRN1 reactions [110] which constitute perhaps the largest class of fragmentation reactions initiated by photoinduced electron transfer. These reactions are chain processes and photoinduced ET is involved only in the initiation step, which is usually poorly defined. The reactions may also be initiated by other means, not involving absorption of a photon. The SRN1 reactions and related redox-activation processes have been recently extensively reviewed [72a, 110,127] and will not be discussed here. 

Photoreactions employing an electron transfer are discussed. Among these are recent examples of photochemical SRN1 reactions, photoalkylations of carbanions and photoreductions initiated by oxyanions and radical anions. Anions used in their ground state as electron donating quenchers are also considered. Intra ion pair electron transfers as well as the use of anion-like precursors in charge transfer complexes or charge transfer excited states are presented. 

The possibility of a thermally activated electron transfer from an anion to an acceptor is not always excluded. As explained by Bordwell [106], this will of course depend on the oxidation potential of the anion or on its related basicity and this author has shown that the electron transfer reactivity of carbanions rapidly decreases with a decrease of basicity. It is thus possible that among the dark SRN1 reactions some of them are activated by an initial ground state electron transfer from the anion to the accepting substrate. 

SRN1 reactions in which anions are not the initial excited species will of course take their place among these reactions but we shall not comment again about these systems. 

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... 

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... 

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). 

In the initially proposed mechanism, the intermediate 2-nitro-2-propyl radicals, Me2(N02)C, undergo two reactions with the more basic (nucleophilic) thiolates addition of thiolates leading to SRN1 products (Equation 10.20 in Scheme 10.32), and SET to yield the nitro anion and thiyl radicals (RS ), Equation 10.21, which combine to give disulfide. 

For nucleophiles which are unable to initiate the reaction but are quite reactive in the propagation steps, the addition of minute amounts of another nucleophile capable of initiating the reaction increases the generation of intermediates. This allows the less-reactive initiation-nucleophile to start its own propagation. This entrainment reaction allows an extension of the SRN1 mechanism to nucleophiles that are poor donors, supporting the chain nature of the reaction [9]. 

Electron-catalyzed (or electron-stimulated) processes constitute a relatively new class of reactions of great potential synthetic interest (Zelenin and Khidekel, 1970 Linck, 1971). Foremost among these ranks the SRN1 mechanism, which is an electron-initiated radical-chain mechanism of nucleophilic substitution (21-24 X- = halide ion) (for reviews, see Kornblum, 1975 Bunnett, 1978, 1982). The initiation step (21) can be performed photochemically, electrochemically, or by adding alkali metal (Pinson and Saveant, 1978 Amatore et al., 1979 van Tilborg et al., 1977, 1978 Saveant, 1980). 

The best known PET bond cleavage reaction involves the substitution of aryl halides by the S l mechanism. This mechanism was first recognized by Bunnett and Rossi in 1970 [55]. The SRN1 mechanism [56,57] requires one-electron reduction of an aryl halide to initiate the substitution reaction. The anion-radical undergoes... 

Electro chemically reducible nitro- and cyanoarenes are used as mediators for SRN1 per-fluoroalkylation of heteroaromatics such asuracils (17) [15], purines (18), pyrimidines (19) [16], indoles (20), and imidazoles (21) [17] where the electroreductively generated arene anion radicals initiate the SET reaction [18] (Scheme 2.37). 

An Sn2 reaction, depicted in equation 1, seems to come about by an electron pair on the nucleophile displacing a second electron pair—the R-X a bond. Four valence electrons appear to be involved. The problem with this representation is that the electronic rearrangement seems radically different from that in a SET process, such as the initiation step of the SRN1 process (7), equation 2. Clearly, just a single electron has been transferred from the nucleophile to RX. As a consequence of these quite different descriptions, the relationship between the two processes becomes obscure. What factors encourage one pathway over the other is not clear. 

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