Radical cyclization of 2-alkenylthioanilides: A Novel synthesis of 2,3- disubstituted indoles [7]

Journal of the American Chemical Society

Volumn 121, Issue 15, 1999, Pages 3791-3792

  Tokuyama, Hidetoshi ^a   Yamashita, Tohru ^a   Reding, Matthew T ^a   Kaburagi, Yosuke ^a   Fukuyama, Tohru ^a  

^a UNIVERSITY OF TOKYO   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ANILIDE; INDOLE DERIVATIVE; THIONAMIDE;

ANALYTIC METHOD; BROMINATION; CYCLIZATION; DRUG SYNTHESIS; HYDROLYSIS; LETTER; METHODOLOGY;

EID: 0033594438     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja983681v     Document Type: Letter

References (23)

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4. Reference 2, Chapter 7.
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14. While comparable results were obtained using benzene, acetonitrile, or THF as solvents, the reaction was sluggish in ethanol and tert-butyl alcohol.
15. 4. Filtration and concentration on a rotary evaporator afforded the crude product. The desired indole was purified by flash column chromatography on silica gel.
16. Under thermal conditions with AIBN as the radical initiator, however, cis and trans substrates afforded the corresponding indoles in comparable yields. For example, the reaction of trans-8 was complete in 45 min at 80°C to afford 9 in 75% yield.
17. The corresponding phenylthioamide and phenylethynylthioamide did not afford the desired indoles under the reaction conditions. Thioformamides afforded the corresponding formamide.
18. A reduction of enantiomeric excess occurred during the conversion of the corresponding amide to the starting thioanilide (Lawesson's reagent (2 equiv) and pyridine (5 equiv) in toluene at 100°C). Addition of pyridine was required to prevent further epimerization.
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23. See the Supporting Information for detailed experimental procedures.