Indoles photocyclization reactions

Two classes of photocyclization reactions of indoles are well exemplified in the literature. One is based on a 6-ti electrocyclic closure of trienes to cyclohexadienes where the indole C2-C3 bond forms part of the triene. The other involves photolysis of m-haloalkylindoles whereupon the halogen-substituted carbon becomes attached to an indole ring position. The first example of the former reaction was reported by Szmuszkovicz [75], who found that UV light irradiation of 2,3-bis-(para-methoxyphenyl)indole in the presence of iodine gave the carbazole 71 (Scheme 37). By analogy with the photocyclization reaction of other 1,2-diarylethenes [76], this reaction presumably proceeds via conrotatory closure of the indole singlet excited... 

Numerous other examples of the dienamide photocyclization reaction in the synthesis of berbine, protoberberine, benzophenanthridine, Amaryllidaceae, and indole alkaloids have been discussed elsewhere. ... 

The photocyclization of iV-vinylanilines is an e.xarnple of a general class of photocyclizations[l]. If the vinyl substituent has a potential leaving group or the reaction is carried out so that oxidation occurs, the cyclization intermediate can aromatize to an indole. 

Enamides 163 undergo photochemical conrotatory six-electron electrocyclic reactions to yield the dihydro intermediate 164, which in turn yields the fraws-fused cyclic product 165 (equation 105) by a (l,5)-suprafacial hydrogen shift. Several natural product syntheses like that of benzylisoquinoline and indole type alkaloids can be achieved by this type of photocyclization (equations 106163, 107164, 108165 and 109166). 

The first method for the preparation of tetrahydroazocino[4,5,6-cd]indoles was reported in 1966. In succeeding years, this reaction came to be known as the Witkop photocyclization. 

Beccalli et al. reported a new synthesis of staurosporinone (293) from 3-cyano-3-(lH-indol-3-yl)-2-oxo propionic acid ethyl ester (1464) (790). The reaction of 1464 with ethyl chlorocarbonate and triethylamine afforded the compound 1465, which, on treatment with dimethylamine, led to the corresponding hydroxy derivative 1466. The triflate 1467 was prepared from 1466 by reaction with trifluoromethanesulfonic anhydride (Tf20) in the presence of ethyldiisopropylamine. The palladium(O)-catalyzed cross-coupling of the triflate 1467 with the 3-(tributylstannyl)indole 1468 afforded the vinylindole 1469 in 89% yield. Deprotection of both nitrogen atoms with sodium ethoxide in ethanol to 1470, followed by photocyclization in the presence of iodine as the oxidizing agent provided the indolocarbazole 1471. Finally, reductive cyclization of 1471 with sodium borohydride-cobaltous chloride led to staurosporinone (293) in 40% yield (790) (Scheme 5.248). 

It is well established that 3-alkyl pyridines are selectively reduced at N1-C2, to produce 3-alkyl-l,2-DHPs [58,59,60], 5-Alkyl-l,2-DHPs, which result from hydride addition at C-6, are potentially valuable synthetic intermediates [61]. Substituent effects on the regiochemistry of the reduction of A-carbalkoxypyridinium salts have been studied in detail by Sundberg [62]. These DHPs have served as useful dienes for the synthesis of ISQs. Methyl 2-[l-phenylsulfonyl-lH-indol-2-yl]-2-propenoate (62) served as dienophile in most of these reactions [61,62,63,64,65,66,67,68]. Palladium-catalyzed radical cyclization [63], photocyclization [64] or thermal cyclization [61,65,66,67,68] reactions have all been employed to furnish the Diels-Alder adducts (e.g., 63). 

As can be seen from the foregoing, phthalimide photocyclizations have provided useful synthetic routes to a variety of heterocyclic products. Machida et al. have used the reaction to yield the spiro compounds (325) from the irradiation (in methanol) of the phthalimide derivatives (326). The products are presumed to be formed via bond formation in the biradical produced by the addition of methanol to the radical cation/r ulical anion pair. The indoles (327) undergo photochemical (2-f-2)-addition with A methyl phthalimide to afford the oxetan adducts (328). This work has also been the subject of a patent application. " ... 

Photocyclization of iV-chloroacetyl amines has been used previously in the synthesis of nitrogen heterocycles, and the reaction of the substituted amine (166) leads to a benzazepinone that can be elaborated to give pseudoprotopine alkaloids. Y-Chloroacetyl derivatives of the seven isomeric indolylethylamines give azepinoindoles and azocinoindoles by photocyclization. Quantum yields for the reaction are correlated with calculated (CNDO/2 and INDO) electron densities, and on this basis mechanisms are suggested the conclusion is that both indole radical cations and indolyl radicals (for the 1-substituted compounds) are... 

Indoles substituted at C-3 with butadienyl or styryl groups undergo electrocyclic reactions to give carbazole derivatives. The silyl enol ether (275) can be converted thermally directly into the carbazole (276), as the result of ready elimination of methanol this sequence is crucial for a hyellazole synthesis (Equation (96)) <89CC43>. Several related 3-styrylindole sequences have been developed and differ with respect to the placement of ethyl carbonate groups on the alkene. Both the substrates (277) and (279) undergo photocyclization to the respective benzocarbazoles (278) and (280) as a result of... 

Experimental data on photocyclization of stilbenes and related indolic compounds such as bisphenylazostilbene were reported in Ref [5]. The stereoselectivity of the formation of macrocyclic stilbenes as well as the regioselectivity of their photocyclization are strongly influenced by the length of the connecting alkanediyl chain [6]. Photochemical cyclization reaction in cis-3,3, 5,5 -tetramethoxystilbene was investigated [7]. The reaction occurred to give dihydrophenanthrene-type... 

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