Brønsted acid catalyzed C3-selective propargylation and benzylation of indoles with tertiary alcohols

Synlett

Volumn , Issue 7, 2008, Pages 975-978

  Sanz, Roberto ^a   Miguel, Delia ^a   Álvarez Gutiérrez, Julia M ^a   Rodríguez, Félix ^b  

^a UNIVERSITY OF BURGOS   (Spain)

^b UNIVERSITY OF OVIEDO   (Spain)

Author keywords

Alcohols; Alkylations; Catalysis; Indoles; Nucleophiles

Indexed keywords

BENZYL ALCOHOL; BRONSTED ACID;

ARTICLE; BENZYLATION; CATALYST; CHEMICAL REACTION; CHEMICAL STRUCTURE; MASS FRAGMENTOGRAPHY; METHODOLOGY; STATISTICAL SIGNIFICANCE; SYNTHESIS;

EID: 42949118893     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2008-1072584     Document Type: Article

References (37)

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24. (a) While preparing this manuscript some works about this reaction using different Lewis acids as catalysts appeared (see ref. 10b-e). We have also reported a single example about the Brønsted acid catalyzed alkylation of indoles with propargylic alcohols: Sanz, R.; Martínez, A.; Álvarez-Gutiérrez, J. M.; Rodríguez, F. Eur. J. Org. Chem. 2006, 1383.
25. (b) Remarkably, in all these reactions only secondary propargylic alcohols are used.
26. The absence of examples where tertiary alcohols are used is probably due to their high tendency to undergo elimination processes under the acidic conditions. Only the alkylation of N-methylindole with 2-phenylpropan-2-ol has been reported. See ref. 10c and 11a.
27. See ref. 12 and also: (a) Sanz, R.; Martínez, A.; Miguel, D.; Álvarez-Gutiérrez, J. M.; Rodríguez, F. Adv. Synth. Catal. 2006, 348, 1841.
28. (b) Sanz, R.; Miguel, D.; Martínez, A.; Álvarez- Gutiérrez, J. M.; Rodríguez, F. Org. Lett. 2007, 9, 717.
29. (c) Sanz, R.; Miguel, D.; Martínez, A.; Álvarez- Gutiérrez, J. M.; Rodríguez, F. Org. Lett. 2007, 9, 2027.
30. (d) Sanz, R.; Martínez, A.; Álvarez-Gutiérrez, J. M.; Rodríguez, F. Synthesis 2007, 3252.
31. (e) Sanz, R.; Martínez, A.; Guilarte, V.; Álvarez- Gutiérrez, J. M.; Rodríguez, F. Eur. J. Org. Chem. 2007, 4642.
32. Alkynols 2 were synthesized by nucleophilic addition of the alkynylcerium reagents to the corresponding aryl alkyl ketones as previously described: Imamoto, T.; Sugiura, Y.; Takiyama, N. Tetrahedron Lett. 1984, 25, 4233.
33. 23N: 349.1830; found: 349.1836.
34. A dialkyl-substituted alkynol, such as 2-methyl-4-phenyl-3-butyn-2-ol, gave a low yield (28%) of the corresponding propargylated indole when reacted with 1a.
35. Alkynols 4 were prepared by addition of phenylethynyllithium to the corresponding 2-cycloalken-1-one at low temperature in THF.
36. Trace amounts of the corresponding product coming from a direct attack of the indole on the propargylic position were observed in the crude of the reactions when alcohols 4b and 4c were used.
37. Alcohols 6a and 6c are commercially available. Alcohol 6b was synthesized by addition of n-BuLi to acetophenone at low temperature in THF.