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

1-Aryl-1,2,3,4-tetrahydroisoquinolines are important structural motifs and are widely found in bioactive molecules, pharmaceutical 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 the recent advances in direct arylation of tetrahydroisoquinolines for the synthesis of title compounds in the absence of metal salt. Also, the emphasis has been put on the 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 Conclusions and Outlook