Palladium-catalyzed acylation of a 1,2-disubstituted 3-indolylzine chloride

Tetrahedron Letters

Volumn 38, Issue 27, 1997, Pages 4749-4752

  Faul, Margaret M ^a   Winneroski, Leonard L ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INDOLE DERIVATIVE; PALLADIUM;

ACYLATION; ARTICLE; CATALYSIS; CHEMICAL REACTION; DRUG SYNTHESIS;

EID: 0030975042     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)01028-9     Document Type: Article

References (28)

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11. The 3-bromoindole 4a was prepared as follows: 0.95 equiv of N-bromosuccinimide in 100 mL THF was added to a suspension of 37 mmol of 3 in 100 mL of THF over 30 min at -10 °C. The reaction was worked up extractively after 15 min and the product crystallized from 4/1 hexanes/acetone to afford 77% of 4a.
12. Halogen metal exchange was confirmed by both deuterium quench experiments and reaction of Sa with methyl iodide.
13. The 3-iodoindole 4b was prepared as follows: 1.0 equiv of N-iodosuccinimide in 25 mL THF was added to a suspension of 11 mmol 3 in 25 mL of THF over 20 min at rt. The reaction was worked up extractively after 30 min and the product purified by flash chromatography using 4/1 hexanes/EtOAc to afford 78% of 4b
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22. The reactions were very selective and compound 3 was the major reaction by-product formed during preparation of 7a-e under the optimal conditions.
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25. Higher yields of 3-(2-haloacyl)indoles (49%) have been obtained by reaction of indole with N-acylpyridinium salts although preparation of 7e using these conditions was unsuccessful: Bergman, J.; Backvall, J. E.; Lindstrom, J. O. Tetrahedron 1973, 29, 971.
26. Reaction of 5a with 2-chloro-N-methoxy-N-methylacetamide afforded 7e in only a 14% yield.
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28. 2 Cl: C, 68.90; H, 5.14; N, 4.46; Found: C, 68.77; H, 5.04; N, 4.47.