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Synfacts 2022; 18(12): 1313
DOI: 10.1055/s-0042-1753122
Metals in Synthesis

Introducing the Magic Methyl: Enantioselective Hydro­methylation of Olefins under Copper Hydride Catalysis

Contributor(s):
Martin Oestreich
,
Hendrik F. T. Klare
,
Daniel Brösamlen
Dong Y, Shin K, Mai BK, Liu P, *, Buchwald SL. * University of Pittsburgh and Massachusetts Institute of Technology, Cambridge, USA
Copper Hydride-Catalyzed Enantioselective Olefin Hydromethylation.

J. Am. Chem. Soc. 2022;
144: 16303-16309
DOI: 10.1021/jacs.2c07489
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Key words

copper catalysis - hydromethylation - methyl group - olefins

Significance

Liu, Buchwald and co-workers have disclosed a copper hydride catalyzed direct enan­tioselective hydromethylation of styrene derivatives. The mild reaction protocol tolerates various functional groups, heterocycles and pharmaceutically relevant frameworks. The installation of a methyl group can have profound effects in drug discovery, also known as the ‘magic methyl effect’.


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Comment

Mechanistic studies including DFT calculations support the shown mechanism. The presence of catalytic amounts of iodide ions is crucial for the asymmetric hydromethylation, transforming the methyl tosylate into the active methylating agent, that is methyl iodide.


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Publication History

Article published online:
17 November 2022

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