Transition-Metal-Free Strategies for the Synthesis of C-1 Aryl-Substituted Tetrahydroisoquinolines

Abstract

1-Aryl-1,2,3,4-tetrahydroisoquinolines are important structural motifs and are widely found in bioactive molecules, pharmaceuticals and synthetic drugs. In view of increasing environmental awareness, the development of transition-metal-free strategies for the synthesis of these compounds is highly desirable. Metal-free oxidative coupling and lithiation methodologies have emerged as effective tools in this area as they exclude the use of transition-metal catalysts and help in reducing unwanted and toxic-metal-based chemical waste in the environment. This review highlights recent advances on the direct arylation of tetrahydroisoquinolines for the synthesis of the title compounds in the absence of a metal salt. Also, the emphasis has been placed on mechanistic considerations of these reactions.

1 Introduction

2 Arylation of Tetrahydroisoquinolines via Oxidative Coupling

2.1 Arylation Using Grignard Reagents

2.2 Arylation Using Other Organometallic Reagents

2.3 Arylation Using Aryl Organoboranes or Arenes

3 Arylation of Tetrahydroisoquinolines via Lithiation

3.1 Intermolecular Arylation

3.2 Intramolecular Arylation

4 Conclusion and Outlook

Key words

arylation - tetrahydroisoquinolines - oxidative coupling - lithiation - C–H activation - coupling reactions

Publication History

Received: 05 November 2020

Accepted after revision: 30 December 2020

Accepted Manuscript online:
30 December 2020

Article published online:
27 January 2021

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