The quest for magic: recent advances in C(sp3)–H methylation
Name
10.1515_pac-2021-1203.pdf
Description
Published version
Size
1.53 MB
Format
Adobe PDF
Checksum (MD5)
43c52ec212dd7f02850a97c997bff5d0
Author(s)
Feng, Kaibo
Date Issued
April 21, 2022
Journal
Pure and Applied Chemistry
Publisher
Walter de Gruyter GmbH
Citation
Feng, Kaibo. "The quest for magic: recent advances in C(sp3)–H methylation" Pure and Applied Chemistry, vol. 94, no. 5, 2022, pp. 547-558.
Version
Final published version
Abstract
Frequently referred to as the “magic methyl” effect, the introduction of a methyl group into a biologically active molecule has the potential to drastically alter its physical and biological properties and significantly increase potency. This effect is most pronounced when the methyl group is added at the α-position of an aliphatic heterocycle or ortho to a large rotatable group on an aromatic ring. Although seminal developments in C–H activation strategies offered solutions to the latter, until recent years there had been no selective and functional-group-tolerant method for C(sp3)–H methylation at late stages of synthesis. For many years, the lack of a generally applicable methylation strategy necessitated arduous de novo synthesis approaches to access methylated drug candidates, and discouraged further investigation and understandings of the magic methyl effect. This review will provide a summary of the most recent advances that enabled non-directed late-stage C(sp3)–H methylation, including through hydride transfer, chemical or anodic oxidation, and photocatalytic hydrogen atom transfer.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivatives
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1515/pac-2021-1203
