A Short Approach to N-Aryl-1,2,3,4-tetrahydroisoquinolines from N-(2-Bromobenzyl)anilines via a Reductive Amination/Palladium-Catalyzed Ethoxyvinylation/Reductive N-Alkylation Sequence

Abstract

N-Aryl-1,2,3,4-tetrahydroisoquinolines are obtained via a convenient and short protocol with a broad range of substituents on both aromatic rings and high functional group tolerance. Starting from readily available ortho-brominated aromatic aldehydes and primary aromatic amines, condensation of these building blocks under reductive conditions gives N-aryl 2-bromobenzylamines. The C-3/C-4-unit of the tetrahydroisoquinoline is introduced using commercially available 2-ethoxyvinyl pinacolboronate under Suzuki conditions. Finally, the obtained crude ortho-ethoxyvinyl benzylamines are cyclized via an intramolecular reductive amination using the combination of triethylsilane/TFA to give the desired N-aryl-1,2,3,4-tetrahydroisoquinolines.

Key words

N-aryl-1,2,3,4-tetrahydroisoquinolines - reductive cyclization - Pd-catalyzed ethoxyvinylation - reductive N-alkylation - cross-coupling

Publication History

Received: 20 October 2020

Accepted after revision: 30 November 2020

Article published online:
07 January 2021

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