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
