Cyclization reactions donor radical cations

Cyclization Reactions Involving Radical Cations and Radical Anions in Linked Donor-Acceptor Systems... 

Intermolecular addition and addition-cyclization reactions of aminium cation radicals with electron-rich alkenes such as ethyl vinyl ether (EVE) allow an entry into products containing the N—C—C—O moiety of 13-amino ethers 70 or the equivalent of /3-amino aldehydes 71. The mild conditions under which aminium cation radicals are generated from PTOC carbamates makes the reactions described in Scheme 22 possible. In the absence of hydrogen atom donors, the /3-amino ethoxy(2-pyridylthio) acetal 71 was the major product. The mixed acetal can easily be converted... 

A further variation of these functionalizations of cyanoarenes is the NOCAS process [14, 15]. As shown in Scheme 14.2, path g, this involves the addition of a nucleophile (which is often the solvent) to the donor radical cation. The thus-formed neutral radical adds to the acceptor radical anion, while rearomatization by the loss of an anion leads again to an overall ipso-substitution. AUenes could be used as the donors in these reactions, as shown recently by Arnold [50]. Accordingly, the irradiation of TCB in the presence of tetramethylaUene (15) in a 3 1 MeCN/MeOH mixture afforded 1 1 1 arene-allene-methanol adduct 16 in 48% yield (Scheme 14.9, central part). Interestingly, the addition of methanol took place exclusively at the central allene carbon, while aromatic substitution occurred through the terminal carbons. co-Alkenols, in which an O-nucleophile and an easily oxidized moiety are both present, could also be used. In the latter case, the initial ET was followed by a cyclization, yielding aryl-substituted tetra-hydrofurans or tetrahydropyrans as the final products via a tandem Ar—C, C—O bond formation [51]. 

For clarity and convenience the following examples of radical-ion cyclization reactions are compiled according to the type of the electron donor from which the radical cation is generated. 

The photolysis of donor-acceptor systems shows a reaction pattern of unique synthetic value. Direct irradiation of the donor-acceptor pairs, such as arene-amine, leads by intramolecular electron transfer, to amine radical cations and arene radical anions. The generated radical cation and radical anion intermediates undergo cyclization reactions providing efficient synthetic routes to N-heterocycles with a variety of ring sizes. 

Likewise, benzyldihydroisoquinolinium derivatives can be used in a photochemical synthesis of tetrahydroisoquinolines. Thus, 2-(2-trimethyl-silylmethylphenylmethyl)-3,4-dihydroisoquinoliniun perchlorates have been successfully cyclized, as in the synthesis of the protoberbine alkaloids (+)xylopinine and (+)stylopine. The reaction proceeds via SET from the xylyl donor to the iminium moiety, fragmentation of the benzylsilane radical cation and carbon-carbon bond formation in the intermediate diradical. The synthesis is rather general and the yields compare favorably with those obtained from related substrates via a dipolar cycloaddition methodology [298] (Sch. 27). 

Interest in CdS mediated surface photochemistry has continued. The irradiation (wavelenyth > 420 nm) of the alkene (3) in an aerated suspension of CdS results in the formation of the products shown in Scheme 1. Under deaerated conditions all the products shown apart from the ketone (4) are formed. The results obtained are interpreted as involving electron transfer from the alkene to the CdS affording a radical cation (5). Subsequent cyclization and back electron transfer or disproportionation yields (6) and (7). Deprotonation followed by back electron transfer or disproportionation yields (8) and (9). The reactions described were all quenched when irradiation was carried out in the presence of the electron donor, 1,2,4,5-tetramethoxybenzene. A comparison of various CdS samples was carried out. 

The photo-NOCAS process has also been reported with P-myrcene (57) as the reactant. The resultant radical cation, generated using dicyanobenzene as the sensitiser, affords the five products (58-62) shown and cyclization within the myrcene radical cation is an essential feature of this reaction sequence. SET photochemistry of aliphatic electron donors can provide a source of radicals. Thus irradiation of donors such as (63), (64), (65) and (66) results in bond fission and the formation of alkyl radicals which undergo addition to alkenes e.g. 67) or alkynes e.g. 68) to give the adducts (69) and (70), respectively. ... 

As already indicated, carbonyl compounds such as ketones, aldehydes, enones, and quinones possess the property to act as effective electron acceptors in the excited state for generating radical anions in the presence of electron-donating partners such as alkenes, aromatics, ruthenium complexes, amines, and alcohols. We will not consider the reactivity of enones and quinones, but we will focus our attention on the behavior of the radical anions formed from ketones and aldehydes. Four different processes can occur from these radical anions including coupling of two radical anions and/or coupling of the radical anion with the radical cation formed from the donor, abstraction of hydrogen from the reaction media to produce alcohols, cyclization, in the case of ce-unsaturated radical anions, and fragmentation when a C -X bond (X=0, C) is present (Scheme 18). 

More elaborate functionalizations could be accomplished when the donor or the radical cation underwent more complex reactions. As an example, the above synthesis of alkyltricyanobenzenes could be varied into a ROCAS reaction (Scheme 14.9, right part) [48, 49]. Thus, photolysis of a mixture of TCB as acceptor, 2-methyl-2-phenyl-l,3-dioxolane (13) as donor and an electron-poor olefin formed a 3-aryl substituted 2-pentanone, which cyclized during purification on silica gel to afford isocoumarine 14 in 75% yield [48], This three-component reaction is based... 

More recently, elegant mechanistic studies on intramolecular Meer-wein reactions by Beckwith et al. considerably extended the utility of diazonium salts. They showed that many electron donors could convert an arenediazonium cation into an aryl radical which cyclized in good yield to form dihydrobenzofurans and indolines. The final radical was functionalized as a halide, sulfide, or ferrocene. Thus, the credentials of diazonium salts as electron acceptors were well established, and the stage was set to investigate the interaction between diazonium salts and TTF. 

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