Useful procedures for fluorocyclization of tryptamine and tryptophol derivatives to 3a-fluoropyrrolo[2,3-b]indoles and 3a-fluorofuro[2,3-b]indoles

• Published in: Journal of fluorine chemistry 2014-09, Vol.165, p.7-13
• Main Authors: Fujiwara, Tomoya, Seki, Takayuki, Yakura, Takayuki, Takeuchi, Yoshio
• Format: Article
• Language: English
• Subjects: Bearing; Derivatives; Fluorination; Fluorine; Fluorocyclization; Furo[2,3-b]indole; Indoles; Pyrrolo[2,3-b]indole; Synthesis; Tryptamine; Tryptamines; Tryptophol
• ISSN: 0022-1139; 1873-3328
• DOI: 10.1016/j.jfluchem.2014.05.011

Versatile procedures for fluorocyclization of various kinds of tryptamine and tryptophol derivatives to obtain the corresponding 3a-fluoropyrrolo(furo)[2.3-b]indoles were developed. •Versatile procedures for fluorocyclization of tryptamine and tryptophol derivatives were developed.•Various kinds of 3a-fluoropyrrolo(furo)[2.3-b]indoles were obtained successfully according to our procedures.•N-fluoro-2,4,6-trimethylpyridinium triflate (FP-T300) or Selectfluor™ is effective for fluorocyclization.•Electron-withdrawing groups at the indole nitrogen or 5-position lowers reactivity of fluorocyclization.•Use of NaHCO3 as an acid trap can improve the yields of acid-labile 3a-fluoropyrrolo(furo)[2.3-b]indoles. Versatile procedures for fluorocyclization of various tryptamine and tryptophol derivatives to obtain the corresponding 3a-fluoropyrrolo[2.3-b]indoles and 3a-fluorofuro[2.3-b]indoles, respectively were developed employing N-fluoro-2,4,6-trimethylpyridinium triflate (FP-T300) or Selectfluor™ as the electrophilic fluorinating agent. The use of NaHCO3 for fluorocyclization was effective in improving the yield of acid-labile fluoropyrrolo(furo)indoles. Our procedures are especially useful for the synthesis of fluoropyrrolo(furo)indoles bearing a free NH indole group.