Single-electron transfer radical cyclization

Amatore C, Thiebault A, Verpeaux J-N (1989) Unexpected single electron-transfer catalyzed cyclization of prenyl sufore dimer - evidence for radical-anion coupling in the outer-sphere oxidation of prenyl sulfone carbanion. J Chem Soc Chem Commun 20 1543-1545... 

Pandey and co-workers have generated arene radical cations by PET from electron-rich aromatic rings [119]. The photoreaction is apparently initiated by single-electron transfer from the excited state of the arene to ground state 1,4-dicyanonaphthalene (DCN) in an aerated aqueous solution of acetonitrile. Intramolecular reaction with nucleophiles leads to anellated products regio-specifically. The author explains the regiospecifidty of the cyclization step from... 

The cyclization process can be promoted by using a single electron transfer mediator. Electron transfer from the mediator generates the carbonyl radical-ion away from the electrode surface so that cyclization can occur before there is opportunity for a second electron transfer. Thus reduction of 16, R = Me, in dimethyl-forraaraide at mercury in the presence of tetraethylammonium fluoroborate leads only to conversion of the ketone function to the secondaiy alcohol. However addition of a low concentration of N,N-dimethyl pyrrolidinium fluoroborate alters the course of reaction and the cyclized tertiary alcohol is now formed. This pyrrolidinium salt is reduced at -2.7 V vs. see at mercuiy to yield a complex DMP(Hg5) which is thought to act as a single electron transfer mediator [94]. Cyclization can... 

A novel synthesis of 5,6-dihydro-4//-1,2-oxazines (20) is presented via the photo-induced cyclization of y. d-unsaturated oximes (21) see Scheme 4. Irradiation of (21) in the presence of 9,10-dicyanoanthraccnc (DCA) led to the heterocycle (20) only. The proposed mechanism proceeds via the radical cation (22), generated by single-electron transfer (SET) from the oxime (21) to the excited sensitizer (DCA. Cyclization of (22) affords the oxazine (20) after proton transfer to the DCA radical anion (DCA ) and H abstraction.61... 

The construction of the carbazole framework is completed by an iron-mediated oxidative cyclization which proceeds via an initial single electron transfer to generate a 17-electron radical cation intermediate. Iron-mediated oxidative... 

Photo-NOCAS reactions of p-dicyanobenzene with 2-methylpropene in acetonitrile afforded novel 3,4-dihydroisoquinoline derivatives, as shown in Scheme 132 [482], This photoreaction is initiated by a single electron transfer from olefin to p-dicyanobenzene. Acetonitrile as a nucleophile combined with the alkene radical cation and the resulting radical cation adds to the radical anion of 1,4-di-cyanobenzene. Cyclization to the ortho position of phenyl group followed by loss... 

MISCELLANEOUS REACTIONS OF DIHYDROPYRIDINES Additional tests for net hydride transfers initiated by single-electron transfer include the use of substrates in which such pathways would necessarily involve readily ring-opened cyclopropylmethyl or readily cyclized 5-hexenyl radicals. Products from these radical reactions are not formed in NAD+/ NADH dependent enzymic reductions or oxidations (Maclnnes et al., 1982, 1983 Laurie et al., 1986 Chung and Park, 1982). Such tests have also been applied in non-enzymic reductions. Thus cyclopropane rings in cyclopropyl 2-pyridyl ketones, or imines of formylcyclopropane (van Niel and Pandit, 1983, 1985 Meijer et al., 1984) survive Mg+2 catalysed reduction by BNAH or Hantzsch esters but are opened by treatment with tributylin hydride. 

In mechanistic matters, it has been demonstrated that co-alkenyl iodides undergo cyclization onto the vinyl function upon treatment with Me2CuLi, in competition with direct substitution. This, as well as the generation of trityl radical in the reaction of Me2CuLi with trityl chloride, constitutes evidence for single electron transfer in reactions of cuprates with iodides (and, to a lesser extent, bromides)16. The intermediacy of alkyl radicals in the substitution process (equation 12) is likely the source of the aforementioned racemization in reactions of secondary iodides4. 

Despite that the regioselective cyclization of 5-hexenyllithiums could be synthetically useful, in those years there was no real development of this methodology9, probably due to the lack of a convenient and efficient procedure for the preparation of unsaturated alkyllithiums and to the conventional belief that simple alkenes are not thought of as sites of nucleophilic attack. Moreover, this was a period when radical cyclizations and radical cascade reactions came to the fore10, and 5-hexenyl substrates were used as probes for radical intermediates in reactions suspected of proceeding via single-electron transfer (SET). 

Ueda et al. reported a tandem radical addition-cycUzation reaction in aqueous media [184]. This reaction was initiated by single-electron transfer from indium to an alkyl iodide. Fragmentation of the iso-propyl iodide radical anion generated the iso-propyl radical, which triggered the addition/cyclization tandem. Final SET and in situ hydrolysis delivered cyclic sulfonamides in good yield but low stereoselectivity. 

On the other hand, the amount of cyclized product depended strongly on the viscosity of the solvent used [76, 77]. An increase in solvent viscosity would be expected to increase the lifetime of radicals, thus facilitating the cyclization process at the site of single-electron transfer (SET), with subsequent formation of cyclized Grignard, and would reduce the mobility of R at the metal surface, thereby preventing this radical from encountering other radicals (see Table 8). 

Compared with the numerous efficient syntheses based on nucleophilic/electrophilic or concerted (c/. Section 4.2.4) cyclization reactions of carbonyl derivatives, very little synthetic applications have been described that rely on radical-induced ring closure reactions, such as the reductive cyclization of 8-un-saturated iminium salts like (129) using samarium diiodide, which affords (132) as the only bicyclic product (Scheme 62). 2 The reaction is believed to proceed by single electron transfer, going through the a-amino radical (130), which cyclizes in an exocyclic mode to give the denoted product (132) via the benzylic carbon radical (131). 

Jeon, Y. T., Lee, C. P, Mariano, P. S., Radical Cyclization Reactions of a Silyl Amine a,P Unsaturated Ketone and Ester Systems Promoted by Single Electron Transfer Photosensitization, J. Am. Chem. Soc. 1991, 113, 8847 8863. 

The process has been the subject of a patent99. Further study on the same system has clearly established the single electron transfer (SET) involvement of the Ag+ ion. This report gives additional evidence for the generation of the radical 40, formed from 41 by irradiation in benzene solution through a Pyrex filter of the enone/alkene/silver triflate system. The radical thus formed adds to the alkene, which then cyclizes to yield the... 

In several instances, Mannich-type cyclizations can be carried out expeditiously under photochemical conditions. The photochemistry of iminium ions is dominated by pathways in which the excited state im-inium ion serves as a one-electron acceptor. The photophysical and photochemical ramifications of such single-electron transfer (SET) processes as applied to excited state iminium ions have been expertly reviewed. In short, one-electron transfer to excited state iminium ions occurs rapidly from one of several electron donors electron rich alkenes, aromatic hydrocarbons, alcohols and ethers. Alternatively, an excited state donor, usually aromatic, can transfer an electron to a ground state iminium ion to afford the same reactive intermediates. Scheme 46 adumbrates the two pathways that have found most application in intramolecular cyclizations. Simple alkenes and aromatic hydrocarbons will typically suffer addition processes (pathway A). However, alkenic and aromatic systems with allylic or benzylic groups more electrofugal than hydrogen e.g. silicon, tin) commonly undergo elimination reactions (pathway B) to generate the reactive radical pair. 

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