Photo-NOCAS reaction

The presence of hetero-atoms within the system, remote from the alkene double bonds, does not have an adverse influence on the SET processes that occur. Thus irradiation of the diene 33 in benzene solution with 1,4-dicyanonaphthalene as the electron-transfer sensitizer affords the cyclobutane 34 in 78% yield. Various examples of the reaction were described giving cyclobutane derivatives in 54-69% yield. Benzene, or an arene solvent, is vital for the success of the reaction. When acetonitrile is used, allylation of the sensitizer (akin to the photo-NOCAS reaction) results in the formation of the three products 35-3718. (2 + 2)-Cyclization of this type described for 33 is also seen with the dialkenyl ether 38. When 38 is irradiated using X > 350 nm or X > 450 nm in acetonitrile... 

The photochemical nucleophile-olefin combination aromatic substitution (photo-NOCAS) reaction received considerable attention from many groups not only because of its synthetic value because the yields of nucleophile-olefm-arene (1 1 1) adducts can be high but also because of interesting mechanistic details (Scheme 48). 

Scheme 48 Basic mechanism of photo-NOCAS reactions.

Various substituted cyclopropanes have been shown to undergo nucleophilic addition of alcoholic solvents. For example, the electron transfer reaction of phenylcyclopropane (43, R = H) with p-dicyanobenzene resulted in a ring-opened ether 44. This reaction also produced an aromatic substitution product (45, R = H) formed by coupling with the sensitizer anion. This reaction is the cyclopropane analog of the photo-NOCAS reaction, but preceded it by almost a decade. 

The photochemical nucleophile olefin combination, aromatic substitution (photo-NOCAS) reaction, formulated below for 2,3-dimethylbutene-methanol-p-dicyano-benzene, has some synthetic utility. The final step, loss of cyanide ion, is not shown. 

There has been a study of photo-induced intramolecular cyclization of some o-haloarylheterylamines which may lead to pyridof 1,2-a]benzimidazole derivatives.51 Several studies have been reported of photochemical nucleophile-olefin combination, aromatic substitution (photo-NOCAS) reactions with fluoride,52 cyanide,53 or acetonitrile54 acting as the nucleophile, hi the example illustrated in Scheme 3,... 

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... 

In some cases the nucleophilic capture of a radical cation is followed by coupling with the radical anion (or possibly with the neutral acceptor), resulting ultimately in an aromatic substitution reaction. Thus, irradiation of 1,4-dicyanobenzene in acetonitrile-methanol (3 1) solution containing 2,3-dimethylbutene or several other olefins leads to capture of the olefin radical cation by methanol, followed by coupling of the resulting radical with the sensitizer radical anion. Loss of cyanide ion completes the net substitution reaction [144]. This photochemical nucleophile olefin combination, aromatic substitution (photo-NOCAS) reaction has shown synthetic utility (in spite of its awkward acronym). 

The photochemical Nucleophile-Olefin Combination, Aromatic Substitution (Photo-NOCAS) reaction, in Handbook of Organic Photochemistry and Photobiology, 2nd edn (eds W. Horspool and F. Lenci), CRC Press, Boca Raton, pp. 40-1-40-17. 

On the other side, coupling of radical anions with radicals is a key step in the electrochemical reductive t-butylation of aromatic compounds [228], in the photo-NOCAS reaction [229], and for other combinations [87]. 

Scheme 27. Radical anion-radical coupling in the photo-NOCAS reaction [229].

Arnold, D. R., Chan, M. S. W., McManus, K. A., Photochemical Nucleophile Olefin Combination, Aromatic Substitution (Photo NOCAS) Reaction. 12. Factors Controlling the Regiochemistry of the Reaction with Alcohol as the Nucleophile, Can. J. Chem. 1996, 74, 2143 2166. 

In the presence of methanol as solvent and 1,4-dicyanobenzene as acceptor, photoinduced electron transfer from 1,4-bis(methylene)cyclohexane gives 4-(methoxymethyl)-1 -methylenecyclohexane and 4-(4-cyanophenyl)-4-(methoxy-methyl)-l-methylenecyclohexane which arise by nucleophilic attack of the solvent on the radical cations, followed either by reduction and protonation, or by combination with the radical anion of the electron acceptor.These observations are in accordance with the proposed mechanism of the nucleophile-olefin combination, aromatic substitution (photo-NOCAS) reaction. The same group has also investigated the use of cyanide ion as nucleophile and report that irradiation of a mixture of 1,4-dicyanobenzene in the presence of biphenyl as donor, KCN, and 18-crown-6 gives a mixture of (79) and (80). These workers have also extended the scope of NOCAS to fluoride ion. In particular, use of 2,3-dimethylbut-2-ene and 2-methylbut-2-ene gives 4-cyanophenyl substituted... 

The scope of the photochemical nucleophile-olefin combination, aromatic substitution (photo-NOCAS) reaction has been extended to include cyanide. 

The phenanthridine ring of 45 is constmcted via a hydrogen bond-controlled enamide photocyclization. Alkyation of the enamide nitrogen is necessary, otherwise, the substrate decomposes <97SL547>. Spirocyclohexylisoquinolines are obtained photochemically from N-arylenamides of cyclohexyl aldehyde <97SC453>. A dihydroisoquinoline is formed in the photo-NOCAS reaction of isobutylene with 1,4-dicyanobenzene in acetonitrile <97JOC8432>. 

Some interesting photo-NOCAS-type reaction (photochemical nucleophile-olefin combination, aromatic substitution) have been reported by three groups. Arnold has developed the photo-NOCAS reaction as three components photoaddition.Xu et al., reported the intramolecular photocyclization of A-(co-hydroxyalkyl)-tetrachlorophthalimide (138, 141) with alkenes to give medium- and large-ring heterocycles (140,143). These photoreactions proceeded via 1, n-biradicals generated from the nucleophilic attack of alcohols to alkenes between the radical anions of phthalimides and the radical cations of alkenes. 

Mizuno et al., reported a new photo-NOCAS reaction catalyzed by phenanthrene (145). Both of a catalytic amount of tetrabutylammonium cyanide and a cyanide anion eliminated from / -dicyanobenzene (144) were used as a nucleophile in this photoreaction. Yasuda et al., reported a temperature elfect of this photoreaction using flow-microreactor. The quantum yields for the formation of photo-NOCAS products were remarkably enhanced at lower temperatures. ... 

Solvent addition to the alkene radical cation is often preferred to fragmentation in nucleophilic media such as alcohols (this gives rise to another useful photosubstitution process on aromatics, the photo-NOCAS reaction discussed elsewhere in this Handbook). 

The photo-NOCAS reaction was first described by McMahon and Arnold and is a photonucleophilic Sfj2Ar aromatic substitution between dicyanobenzene and an olefin in the presence of electron donor photosensitizers (phenanthrene or biphenyl) in acetonitrile-methanol solutions. This reaction system has been researched extensively in recent times. As shown in Scheme 6, the single electron transfer from olefin to photo-excited electron-deficient dicyanobenzene forms the cation radical of the olefin, which initiates a quenching reaction with nucleophile solvent methanol molecules and forms the methoxyalkyl radical. Addition of an electron transfer photosensitizer (phenanthrene or biphenyl) to the reaction mixture increases the efficiency of the reaction simply by absorbing more Hght. The excited state of the photosensitizer donates an electron to dicyanobenzene to give the photosensitizer radical cation and dicyanobenzene radical anion. The photosensitizer radical cation then oxidizes the olefin. 

The photo-NOCAS reaction with 2,6-dimethyl-l,6-heptadiene gave two major cyclic aryl-methoxy adducts (a cyclohexane and a cycloheptane) as well as an acyclic heptene adduct Variation in concentration of the nucleophile, methanol, and co-donor, biphenyl, has been shown to affect the product ratios. Further applications of the photo-NOCAS S 2Ar reactions with the aUeyl-4-enols, a-terpineol, limonene, 2-methyl-2-butene, 2,3-dimethyl-2-butene, (3-myrcene, and 1,4-bis (methylene) cyclohexene have been reported.The aryl-methoxy adduct product ratios have been investigated and discussed in terms of the stability of radical intermediates and the factors controlling the regiochemistry of reaction with the nucleophiles alcohols, cyanide, and fluoride attempts to justify the results by ab initio molecular orbital calculations have been made. The photo-NOCAS reaction with 2-methylpropene in the absence of methanol and a donor molecule has shown that solvent acetonitrile can act as a nucleophile. Under these conditions a tetrahydroisoquinoline product is formed, prior to HCN elimination, in high yield as illustrated in Scheme 8. The adduct product formation was rationalized on the basis of the relatively high oxidation potential of the olefin. 

Arnold, R.D. and Du, X., The photochemical nucleoplule-olefin combination, aromatic substitution (photo-NOCAS) reaction. Part 5 methanol-monoterpenes (a- and P-pinene, tricyclene and nopol), 1,4-dicyanobenzene, Can. J. Chem., 72,403, 1994. 

The Photochemical Nucleophile-Olefin Combination, Aromatic Substitution (Photo-NOCAS) Reaction... 

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