A synthesis of 3-fluoroindoles and 3,3-difluoroindolines by reduction of 3,3-difluoro-2-oxindoles using a borane tetrahydrofuran complex

Tetrahedron

Volumn 55, Issue 7, 1999, Pages 1881-1892

  Torres, José C ^a   Garden, Simon J ^a   Pinto, Angelo C ^a   Da Silva, Filipe S Q ^b   Boechat, Núbia ^b  

^a FEDERAL UNIVERSITY OF RIO DE JANEIRO   (Brazil)

^b INSTITUTO OSWALDO CRUZ   (Brazil)

Author keywords

Halogenation; Indoles; Indolinones; Reduction

Indexed keywords

BORANE DERIVATIVE; INDOLE DERIVATIVE; TETRAHYDROFURAN DERIVATIVE;

ARTICLE; CHEMICAL ANALYSIS; CHEMICAL REACTION; CHEMICAL STRUCTURE; HALOGENATION; PRIORITY JOURNAL; SYNTHESIS;

EID: 0033548108     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4020(98)01229-0     Document Type: Article

References (61)

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35. CCF 30].
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54. The question that therefore arises is, what is the mechanism that results in the formation of the small quantity of 3 (f and g) during the reduction reaction? We speculate that the formation of these 3-fluoroindoles maybe the result of Lewis acid assisted fluoride ion elimination during reduction of 2 (f and g) or that alternatively either before or after reduction of the amide carbonyl to the borate ester (scheme 1) the gem-difluoromethylene is reduced to a mono-fluoromethylene group. Either possibility may allow elimination of the boronate without participation of the nitrogen, thus forming the respective indoles.
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60. 3-Fluoroindole (3a) has been previously prepared by the treatment of N-acetyl-1,2-difluoroindoline with ethanolic potassium hydroxide. The melting point was described as room temperature, see reference 4a.
61. H2 appears as a triplet due to similar magnitudes of coupling with fluorine and NH. For a further example see Powers, J. C. J. Org. Chem. 1966, 31, 2627-2631, where H2 of 3-chloroindole was observed to couple with the NH (J 2.5Hz).