Search

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 [ABSTRACT FROM AUTHOR]

A simple protocol for the C1 arylation of tetrahydroisoquinolines with aryl Grignard reagents via diethyl azodicarboxylate (DEAD) mediated oxidative C-H activation under metal-free conditions has been developed. The target compounds, including some naturally occurring alkaloids, were obtained in moderate to good yields. [ABSTRACT FROM AUTHOR]

Direct cross-coupling between N-methyltetrahydroiso-quinolines and alkynes using CuI-DEAD is presented. It affords the regioselective C-1-alkynylated products in good yield. This regio-selectivity is in contrast to the results reported earlier in the reaction of N,N-dimethylbenzyl amine where the N-methyl alkynylated product was formed exclusively or predominantly. The C-1-substi-tuted propargylic isoquinolines were easily reduced to phenethyl-isoquinolines with Pd/C. This reaction sequence provides a short route to synthesize methopholine, homolaudanosine and other phenethylisoquinoline alkaloids. [ABSTRACT FROM AUTHOR]