Efficient C(sp3)–H Bond Arylation of Tetrahydroisoquinolines with Knochel-Type Arylzinc Reagents under Oxidative Conditions

Batra²,

et al. 2020

Synthesis

Abstract1-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 Introduction2 Arylation of Tetrahydroisoquinolines via Oxidative Coupling2.1 Arylation Using Grignard Reagents2.2 Arylation Using Other Organometallic Reagents2.3 Arylation Using Aryl Organoboranes or Arenes3 Arylation of Tetrahydroisoquinolines via Lithiation3.1 Intermolecular Arylation3.2 Intramolecular Arylation4 Conclusion and Outlook

Section: Arylation Using Other Organometallic Reagentsmentioning

confidence: 99%

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

Batra²,

et al. 2020

Synthesis

“…The group of Menche revealed CuCl 2 -catalyzed alkylation and benzylation of THIQ derivatives with organozinc reagents . In 2017, our group has demonstrated a novel transition-metal-catalyst-free C(sp 3 )–H bond arylation of tetrahydroisoquinoline (THIQ) derivatives with Knochel-type arylzinc reagents . However, the reports on the reaction of the corresponding less reactive C(sp 3 )–H bonds next to an oxygen atom with less reactive organozinc reagents are scarce.…”

Section: Introductionmentioning

confidence: 99%

“…11 In 2017, our group has demonstrated a novel transition-metal-catalyst-free C(sp 3 )−H bond arylation of tetrahydroisoquinoline (THIQ) derivatives with Knochel-type arylzinc reagents. 12 However, the reports on the reaction of the corresponding less reactive C(sp 3 )−H bonds next to an oxygen atom with less reactive organozinc reagents are scarce. One case was reported by Muramatsu in which Ph 2 Zn was used in the catalytic C(sp 3 )−H bond arylation of isochroman during the optimization process.…”

Section: ■ Introductionmentioning

confidence: 99%

Direct Arylation of Benzyl Ethers with Organozinc Reagents

Peng

Wang

et al. 2018

J. Org. Chem.

Self Cite

“…Palladium-catalyzed migratory insertion of carbon monoxide in the presence of O - and N -nucleophiles, i.e., the alkoxycarbonylation and aminocarbonylation reactions, is among the most widely used homogeneous catalytic reactions in synthetic chemistry. 1 Their importance could be illustrated by the synthesis of simple building blocks and by the functionalization of compounds of biological relevance. 2…”

Section: Introductionmentioning

confidence: 99%

Palladium-Catalyzed Synthesis of Amidines viatert-Butyl isocyanide Insertion

2018

Para -substituted iodobenzenes were reacted with tert -butyl isocyanide and piperidine as nucleophiles in the presence of palladium–diphosphine catalysts. Both single and double insertion of the isocyanide was observed and the corresponding amidines and ketimine–amidines were obtained in yields of practical interest. With the increase of the tert -butyl isocyanide/iodobenzene ratio, 100% chemoselectivity toward the ketimine–amidine was achieved. The formation of the products was rationalized on the basis of a catalytic cycle analogous to that of the aminocarbonylation reactions. Clear connection was found between the activity and the electronic structure of the proposed catalyst Pd(diphosphine) by computational studies, as the more negative partial charge on palladium resulted in higher conversion. Among five isocyanide substrates, only tert -butyl isocyanide was proved to be active.