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Updated: Jul 19, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
A practical synthetic route to functionalized THBCs and oxygenated analogues via intramolecular Friedel-Crafts
Marco Angeli1, Marco Bandini, Andrea Garelli
1Dipartimento di Chimica G. Ciamician, Università di Bologna, via Selmi 2, 40126, Bologna, Italy.
Abstract:
A practical catalytic approach to the synthesis of 4-substituted 1,2,3,4-tetrahydro-beta-carbolines (THBCs, 1) and 1,2,3,9-tetrahydropyrano[3,4-b]indoles (2) via InBr3-catalyzed intramolecular Friedel-Crafts (F-C) cyclization is described. The use of cross-metathesis reaction represents a direct route to the cyclization precursors and the use of InBr3 (5 mol%) allowed polycyclic indole compounds to be isolated in high yields under mild reaction conditions (rt, DCM, minutes). Finally, efforts toward the development of a stereocontrolled version of the present cyclization are presented, highlighting [salenAlCl] and bimetallic [(salenAlCl)2-InBr3] system as promising chiral Lewis acids (ee up to 60%).
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