Synlett 2018; 29(04): 375-382
DOI: 10.1055/s-0037-1609093
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© Georg Thieme Verlag Stuttgart · New York

Recent Progress in Methylation of (Hetero)Arenes by Cross-Coupling or C–H Activation

Lu Hu
a  Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing 100084, P. R. of China   Email: liaoxuebin@mail.tsinghua.edu.cn
,
b  Discovery Chemistry, Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA   Email: yliu2@gnf.org
,
a  Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing 100084, P. R. of China   Email: liaoxuebin@mail.tsinghua.edu.cn
› Author Affiliations
This work was supported by the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua–Peking Centre for Life Sciences and by the 1000 Talents Recruitment Program.
Further Information

Publication History

Received: 24 October 2017

Accepted after revision: 20 December 2017

Publication Date:
05 February 2018 (eFirst)

Abstract

Owing to the ‘magic methyl effect’ on a compound’s physical and biological properties, methylation is a strategy frequently used by medicinal chemists in structure–activity relationship studies or in lead optimization. This article highlights the most recent reported methods for the direct methylation of (hetero)arenes, which mainly involve either C–H functionalization or cross-coupling of methylating reagents with (hetero)aryl halides. Methylation of C–H bonds of (hetero)-arenes, which is atom economical, has been explored by several research groups in recent years. Given the unmatchable availability of (hetero)aryl halides, we believe that Ni-catalyzed methylation using iodomethane or deuterated iodomethane as the methyl source is one of the most convenient methods.

 
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