Electron transfer initiated cyclization

Intramolecular electron transfer initiated cyclization reaction of 7V-allyliminium salt systems may also generate 3-pyrrolidinyl ethers or alcohols in monocyclic and bridged or fused bicyclic systems (e.g. equations 63 - 65)122,123. 

Kumar, V.S. and Floreancig, P.E. (2001) Electron transfer initiated cyclizations cyclic acetal synthesis through carbon-carbon 0-bond activation. Journal of the American Chemical Society 123, 3842-3843. 

Development and applications of electron-transfer-initiated cyclization reactions, particularly, applications to heterocycle synthesis 07SL191. 

A new synthetic pathway for the construction of cyclic acetals (41) from homobenzylic ethers (40) has been recently developed by Floreancig et al. [44]. The electron transfer initiated oxidative cyclization is efficiently catalyzed by A-methylquinolinium hexafluorophosphate (NMQPE6) in the presence of oxygen (Sch. 22). For gram-scale preparations solid Na2S203 has to be used as an additive to suppress decomposition caused by the reactive oxygen species involved. 

Addition Reactions.—As the years go by, the importance of electron transfer processes is becoming increasingly apparent, and hardly a month passes without the reinterpretation of a reaction as involving such a process. This has stimulated the publication of review articles such as that by Mattes and Farid on the electron transfer reactions of alkenes, and the more specific reviews by Mariano on the application of electron transfer photochemistry to iminium salts. In this area Mariano and his co-workers have reported further on the electron-transfer-initiated photochemistry of iminium salts (1), and in detail on the spiro-cyclization methodology of iminium salt cyclization. ... 

The electron-transfer initiated photoaddition of allylsilanes to iminium salts has been examined in detail. Irradiation of l-methyl-2-phenylpyrrolinium perchlorate (177) and the allylsilanes (178) in methanol, for example, gave the 2-allylpyrrolidines (179) " the proposed pathway is outlined in Scheme 11. Photoaddition is initiated by electron transfer and driven to completion by desilylation of the allylsilane-derived cation radical. Analogous conversions have been reported in the allyl iminium perchlorates (180), " and cyclization to the spiro-compounds (181) occurs on irradiation of the /3-enaminone-derived allyliminium salts (182). " A photocyclization of this type has been... 

There are examples of other halomethanes that can undergo radical addition. a-Haloesters have been successfully added to alkenes in the presence of copper metal. The copper serves as an electron transfer initiator. The 7-haloester adduct cyclizes to a lactone. The reaction works best when Nal is also used to convert the bromide to the more reactive iodide. " ... 

The distyrylbenzene derivative (141) is photochemically reactive on irradiation in solution. The solvent of choice is acetonitrile/benzene/water (7 2 1) saturated with ammonia. The reactions encountered with this system are derived from electron transfer initiated by p-dicyanobenzene as the electron accepting sensitizer. This process yields the radical cation (142) of the starting material and also the cyclized radical cation (143). These species are trapped by ammonia to yield the final products (144) and (145) in the yields shown. The naphthyl system [141, R-R = (CH=CH)2] is also reactive and affords the analogous products (146) and (147). A study has examined the photochemically-induced cyclization of tetraenes such as (148) under SET conditions in aqueous acetonitrile solution. A variety of electron accepting sensitizers was used. In the example cited the sensitizer (149) was effective and the cascade cyclization yielded the product (150). 

Horeancig and co-workers also observed neighboring group participation of acetal ethers in the formation of substituted furanoside in their electron transfer-initiated cationic cyclizations. ° Their efforts have provided a method for oxonium ion generation through the one-electron... 

Kumar VS, Aubele DL, Eloreancig PE. Electron transfer initiated heterogenerative cascade cyclizations polyether s3mthesis under nonacidic conditions. Org. Lett. 2002 4 2489-2492. 

The mechanism of the electroreductive cyclization reaction has been studied in some detail [22], The initial thought was that it occurred via the cyclization of the radical anion derived, for example, from 25 in the first reduction step. A moment s reflection, however, reveals that there are many more mechanistically viable pathways, especially when one realizes that the transformation involves five steps - two electron transfers (symbolized below by e and d , the latter corresponding to a homogeneous process), two protonations ( p ), and cyclization ( c ). In principle, these could occur in any order, and with any one of the steps being rate-determining. 

These observations are in accord with a scheme involving a reversible electron transfer, followed by a reaction that depletes the concentration of the initially formed reduced species, R. They are also reminiscent of the observations made earlier in regard to the electrohydrocyclization process. The greater the rate of the follow-up process, the more significant its effect on the concentration of R in a given time period, that associated with the CV scan rate, for example. From a moments consideration of the Nernst equation, it is clear that this event should manifest itself in terms of a shift in the peak potential to a more positive value, as observed for 255 and 257b [4]. In the present instance, it is suggested that a rapid or concerted loss of the mesylate anion in the reductive cyclization is likely to be associated with this so-called kinetic shift of the peak potentials [69]. 

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 electroreductive cyclization reaction of 6-heptene-2-one 166, producing CIS-1,2-dimethylcyclopentanol 169, was discovered more than twenty years ago [166]. In agreement with Baldwin s rules, the 5-exo product is obtained in a good yield. Since that time, the mechanism of this remarkable regio- and stereoselective reaction has been elucidated by Kariv-Miller et al. [167-169]. Reversible cyclization of the initially formed ketyl radical anion 167 provides either the cis or the trans distonic radical anion. Subsequent electron transfer and protonation from the kinetically preferred 168 leads to the major cis product 169. The thermodynamically preferred 170 is considered as a source of the trace amounts of the trans by-product 171 (Scheme 32). 

Intensive studies concerning the photoreductive cyclization of distinct ketones and aldehydes are made by Cossy et al. [170], They describe how bicyclic tertiary cycloalkanols 173 and 174 can be prepared from, s-un-saturated ketones 172 in good yields, initiated by photoinduced electron transfer from triethylamine in acetonitrile or by photoionization in pure hexamethyl-phosphoric triamide (HMPA) [171, 172], The reaction is stereo-, chemo- and... 

Various transition metals have been used in redox processes. For example, tandem sequences of cyclization have been initiated from malonate enolates by electron-transfer-induced oxidation with ferricenium ion Cp2pe+ (51) followed by cyclization and either radical or cationic termination (Scheme 41). ° Titanium, in the form of Cp2TiPh, has been used to initiate reductive radical cyclizations to give y- and 5-cyano esters in a 5- or 6-exo manner, respectively (Scheme 42). The Ti(III) reagent coordinates both to the C=0 and CN groups and cyclization proceeds irreversibly without formation of iminyl radical intermediates.The oxidation of benzylic and allylic alcohols in a two-phase system in the presence of r-butyl hydroperoxide, a copper catalyst, and a phase-transfer catalyst has been examined. The reactions were shown to proceed via a heterolytic mechanism however, the oxidations of related active methylene compounds (without the alcohol functionality) were determined to be free-radical processes. 

With respect to photoinitiation, generally, it is important to be very careful in one s choice of sensitizers. For example, attempts to initiate the cyclization of homobenzylic ethers failed if 1,4-dicyanobenzene was used as a sensitizer. Rapid regeneration of the starting material by back-electron transfer from the dicyanobenzene anion-radical to the substrate cation-radical was the cause of cyclization inefficiency. To slow this unproductive process, a mixture of A-methylquinolinium hexafluorophosphate (sensitizer), solid sodium acetate (buffer), and tert-butylbenzene (cosensitizer) in 1,2-dichloroethane was employed. This dramatically increased the efficiency of the reaction, providing cyclic product yields of more than 90% in only 20 min (Kumar and Floreancig 2001, Floreancig 2007). 

Electroreductive one-electron initiation of cyclization was described for the series of E,E-, 1-dibenzoyl-l,6-heptadiene and its derivatives (Roh et al. 2002, Felton and Bauld 2004). In this case, the catalytic effect was also observed (the actual consumption of electricity was substantially less than theoretical). The same bis(enones) can also be cyclized on the action of the sodium salt of chrysene anion-radical in THF, but with no catalytic effect. Optimum yields were obtained only when 70-120 mol% of the initiator was used, relative to a substrate (Yang et al. 2004). The authors suggest that tight ion pairing of the sodium cation with the product anion-radical in THF (which is a somewhat nonpolar solvent) slows down the intermolecular electron transfer to the bis(enone) molecules. Such an electron transfer would be required for chain propagation. 

Pandey and co-workers developed two photosystems useful for initiating one-electron reductive chemistry and applied them to activate a, 3-unsaturated ketones. The resulting carbon-centered radicals cyclize stereoselectively with proximate olefins. Their concept involved a secondary and dark electron transfer from... 

Triethylamine as the electron donor was also used by Mattay and co-workers in tandem fragmentation cyclization reactions of a-cyclopropylketones. The initial electron transfer on the ketone moiety is followed by the fast cyclopropyl-carbinyl-homoallyl rearrangement, yielding a distonic radical anion. With an appropriate unsaturated side chain within the molecule both annealated and spi-rocyclic ring systems are accessable in moderate yields (Scheme 41) [62]. 

In summary, it would appear that the oxidation of a catecholamine probably first involves the formation of a semi-quinone radical (this can be brought about by an one-electron transfer, e.g. from Cu++ ions,14 or by photoactivation 1) which rapidly undergoes further oxidation (e.g. with atmospheric oxygen) to an intermediate open-chain quinone (such as adrenaline-quinone) and then cyclizes by an oxidative nucleophilic intramolecular substitution to the amino-chrome molecule. Whilst the initial formation of a leucoaminochrome by non-oxidative cyclization of the intermediate open-chain quinone in some cases cannot be entirely excluded at the moment (cf. Raper s original scheme for aminochrome formation72), the... 

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