2- ethyl photocyclization

Scheme 27.—Photocyclization of 2-(2-Azidophenyl)ethyl Esters and 5-Azido-4-(hy-droxymethyl)-l-methoxynaphthalene Esters.

Scheme 44 Tandem intramolecular photocyclization of 2-(l-naphthyl)ethyl w-aniU-noaUcanoate.

Yasuhara et al. reported a total synthesis of furostifoline (224) by the oxidative photocyclization of 3-(indol-2-yl)-2-(isopropenyl)furan (1146), which was obtained by Sonogashira coupling of ethyl 2-ethynylphenylcarbamate (1143) with 3-bromo-2-propenylfuran (1142) (693). 

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). 

Furthermore, it was shown that alpha- as well as ortho-substituents in such ketones retard the photocyclization due to other competing reactions. However, photocyclization showed interesting stereochemical trends, which were also strongly affected by the solvent polarity and the phase (Scheme 8.7). For example, the photocyclization of a-(o-ethyl phenyl acetophenone (27) either in benzene or as a solid favored the isomer with the methyl and phenyl group trans to R, due to the conformational preferences in the 1,5-biradical intermediate [9]. 

Horaguchi and coworkers [19, 20] have studied extensively the effect of solvents and the groups attached to the 8-carbon, and have concluded that polar solvents lower both photocyclization yield and diastereoselectivity. Studies with different substrates have revealed that the development of diastereoselectivity is the result of conformational preferences of the biradical rather than of the steric interactions between the two radicals. The same research group has also studied the photocyclization of ethyl oc-(o-benzoylphenoxy)carboxylates (59), and reported that the product yields and Z/E ratios (60a 60b) in benzene and acetonitrile are, interestingly, much the same as for other ketones in which R is not an electron-withdrawing group [20] (Table 8.2). 

Sharshira, E.M., Okamura, M., Hasegawa, E., and Horaguchi, T. (1997) Photocyclization reactions. Part 6 [1]. Solvent and substituent effects in the synthesis of dihydrobenzofuranols using photocyclization of 2-alkoxybenzo-phenones and ethyl 2-benzoylpheno-xyacetates. Journal of Heterocyclic Chemistry, 34, 861-869. 

Remote photocyclization of (dibenzylamino)ethyl benzoylacetate. Intramolecular hydrogen abstraction through a ten-membered cyclic transition state. Journal of the Chemical Society, Chemical Communications, 363-364. 

The key step in the synthesis of the azaphenanthrene alkaloid eupoulaur-amine 45, is an intramolecular SRN1 reaction of 3-bromo-Af-methyl-A-(2-oxo-2-phenyl-ethyl)-isonicotinamide 44, followed by in situ stilbene photocyclization, and further methylation (Sch. 46). 

The stereochemistry and photocyclization of the corresponding 1 -ethyli-deneenamide 136 has also been studied (24,109). Acylation of the 1-ethyl-isoquinoline with benzoyl chloride afforded a mixture of two enamides of geometrical isomers, the unstable E (136) and stable Z isomers (137), which were easily assigned from the nuclear Overhauser effect data in their NMR spectra (24). 

Archer and co-workers (103) have also employed the Snieckus oxidative pho-tocyclization in the key step of their synthesis of the 7//-pyrido[4,3-c]carbazole ring system (Scheme 40). Thus, a Wittig condensation between pyruvate 242 and pyridine 243 gave the unsaturated ester 244. Photocyclization gave the tetracyclic ester 245. Reduction and reaction with methyl isocyanate led to carbamate 247. Oxidation of alcohol 246 to aldehyde 248, followed by a standard one-carbon homologation, gave the desired ethyl derivative 249. These chemists also synthesized the 10-methoxyl derivative of each compound. 

Numerous examples of photocyclization accompanied by elimination of HCl, HBr or HI have again been described although in most cases details of the reaction mechanism are not clear. Noteworthy examples include the conversion of the N-(hydroxyphenyl-ethyl)-3-(bromophenyl)propionamide (132) into the 11-membered lactam (133) and the syntheses of 4,5,7a,8-tetrahydro-1,2-... 

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... 

In connection with total synthesis in this subgroup, mention may be made of a model synthesis of 5-oxodesethylcatharanthine (242) by the photocyclization of the chloro-amide (243). " Extension of this approach to the synthesis of catharanthine is at present being hindered by the non-availability of the dihydropyridine derivative required for the preparation of the 20-ethyl analogue of (243). 

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