Installing the “magic methyl” – C–H methylation in synthesis
Daniya
Aynetdinova, 
†a
Mia C.
Callens,
†a
Harry B.
Hicks,
†a
Charmaine Y. X.
Poh,
†a
Benjamin D. A.
Shennan,
†a
Alistair M.
Boyd,
‡a
Zhong Hui
Lim,
‡a
Jamie A.
Leitch
*a
and
Darren J.
Dixon
*a
†a
Mia C.
Callens,
†a
Harry B.
Hicks,
†a
Charmaine Y. X.
Poh,
†a
Benjamin D. A.
Shennan,
†a
Alistair M.
Boyd,
‡a
Zhong Hui
Lim,
‡a
Jamie A.
Leitch
*a
and
Darren J.
Dixon
*a
Abstract
The selective and efficient C–H methylation of sp2 and sp3 carbon centres has become a powerful transformation in the synthetic toolbox. Due to the potential for profound changes to physicochemical properties attributed to the installation of a “Magic Methyl” group at a strategic site in a lead compound, such techniques have become highly desirable in modern drug discovery and synthesis programmes. This review will cover the diverse techniques that have been employed to enable the selective installation of the C–Me bond in a wide range of chemical structures, from simple building blocks to complex drug-like architectures.
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