Synthesis of Indoline- and 1,2,3,4-Tetrahydroquinoline-Based Symmetrical Triarylmethanes

We present a novel and efficient, metal-free methodology for the regioselective synthesis of symmetrical triarylmethanes through C-H alkylation of indolines and 1,2,3,4-tetrahydroquinolines with aryl aldehydes. The transformation employs 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as both solvent and promoter, eliminating the need for traditional metal catalysts or directing groups. This method demonstrates exceptional regioselectivity, targeting the C5 position of indolines and the C6 position of tetrahydroquinolines exclusively. The protocol exhibits a broad substrate scope, accommodating diverse aryl aldehydes and heterocyclic substrates under mild conditions. Notably, the reaction proceeds efficiently with both N-H-free and N-benzyl-protected substrates. Mechanistic studies, based on control experiments and literature findings, indicate that the reaction proceeds via iminium intermediates and regioselective C-H functionalization. The practical utility of this methodology is demonstrated through gram-scale synthesis, high HFIP recyclability, and successful late-stage functionalization of complex bioactive molecules. This approach represents a significant advancement in the sustainable synthesis of symmetrical triarylmethanes, offering a valuable tool for applications in pharmaceutical and materials chemistry.

Journal

JOURNAL OF ORGANIC CHEMISTRY

Year

2025

Volume

90

Issue

28

Pages

9954-9964

ISSN

0022-3263

eISSN

1520-6904

DOI

10.1021/acs.joc.5c00960

WoS UID

WOS:001524021000001