Electron Transfer-Initiated Cyclization Reactions

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. 

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

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. ... 

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). 

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). 

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]. 

A significant enhancement of reactivity of the carbonyl compound by complexation with Mg2+ has also been applied to a novel type of carbon-carbon bond formation via photoinduced electron transfer from unsymmet-rically substituted acetal (5) with benzophenone (6) (Scheme 26) [211]. This photochemical reaction takes place in the absence of Mg2+ in MeCN. However, the yield of the desired carbon-carbon coupling product 7 is only 15% together with radical dimers 8 (28%) and 9 (2%). Addition of Mg(C104)2 to this system results in a much higher yield of 7 (e.g., 78%) at the expense of radical dimer formation [211]. Thus, the initial photoinduced electron transfer may be catalyzed by Mg2+ to produce a radical ion pair (6 "-Mg2+5 +), where 6 is stabilized by the complexation with Mg2+, as shown in Scheme 26 [211]. The efficient C-C bond formation occurs in the radical ion pair, followed by cyclization before and after desilylation to produce various types of products (Scheme 26). 

In the course of the reaction, Michael adduct 43 cyclizes initially under base catalysis to the dihydropyridone 45, which forms dianion 46. Electron transfer (an SET process leads to radical anion 47, which is finally transformed into pyridone 44 through an aromati/ation that includes hydrogen transfer and another SET process. 

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 recent publications, Hasegawa et al. were able to show that aromatic (3-oxoesters are also capable for macrocyclization reactions initiated via photoinduced electron transfer. Upon irradiation in benzene, the thioether linked substrates 5 gave the eight-membered thia-lactones 6 in moderate yields (Sch. 7) [21]. Cyclization occurred exclusively at the remote position a to the heteroatom. 

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