Synthesis 2021; 53(20): 3815-3826
DOI: 10.1055/a-1509-8624
paper

Direct Approach to 3-Fluoroindoles and 3,3-Difluoroindolines from 2,2-Difluoro-2-phenylethan-1-amines via C–H/N–H Coupling

Lanfei Zhang
a   Department of Chemistry, Shanghai University, 99 Shang Da Road, Shanghai 200444, P. R. of China
b   State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Science, 555 Zu Chong Zhi Road, Shanghai 201203, P. R. of China
,
Xiaofei Zhang
b   State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Science, 555 Zu Chong Zhi Road, Shanghai 201203, P. R. of China
,
Yongmei Cui
a   Department of Chemistry, Shanghai University, 99 Shang Da Road, Shanghai 200444, P. R. of China
,
Chunhao Yang
b   State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Science, 555 Zu Chong Zhi Road, Shanghai 201203, P. R. of China
› Author Affiliations
This work was supported by grants from Science and Technology Commission of Shanghai Municipality (18431907100), and by the State Key Laboratory of Drug Research (SIMM193ZZ-03).


Abstract

Herein, a direct method for the synthesis of 3-fluoroindoles and 3,3-difluoroindolines from easily accessible 2,2-difluoro-2-phenyl­ethan-1-amines is presented. This protocol was performed by Pd-catalyzed direct C–H/N–H coupling and employed picolinamide as a directing group. By controlling the temperature for this transformation, various 3,3-difluoroindolines and 3-fluoroindoles could be isolated with moderate to good yields.

Supporting Information



Publication History

Received: 21 April 2021

Accepted after revision: 17 May 2021

Accepted Manuscript online:
17 May 2021

Article published online:
15 June 2021

© 2021. Thieme. All rights reserved

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