Modular radical cross-coupling with sulfones enables access to sp3-rich (fluoro)alkylated scaffolds

Article abstract of DOI:10.1126/science.aar7335

Cross-coupling chemistry is widely applied to carbon-carbon bond formation in the synthesis of medicines, agrochemicals, and other functional materials. Recently, single-electron-induced variants of this reaction class have proven particularly useful in the formation of C(sp²)-C(sp³) linkages, although certain compound classes have remained a challenge. Here, we report the use of sulfones to activate the alkyl coupling partner in nickel-catalyzed radical cross-coupling with aryl zinc reagents. This method's tolerance of fluoroalkyl substituents proved particularly advantageous for the streamlined preparation of pharmaceutically oriented fluorinated scaffolds that previously required multiple steps, toxic reagents, and nonmodular retrosynthetic blueprints. Five specific sulfone reagents facilitate the rapid assembly of a vast set of compounds, many of which contain challenging fluorination patterns.

Full text of DOI:10.1126/science.aar7335

Cite as: R. R. Merchant et al., Science
10.1126/science.aar7335 (2018).
α
First release: 18 February 2018
www.sciencemag.org
(Page numbers not final at time of first release) 1

α
α
First release: 18 February 2018
www.sciencemag.org
(Page numbers not final at time of first release)
2

→
→
α
First release: 18 February 2018
www.sciencemag.org
(Page numbers not final at time of first release)
3

α
α
α
α
α
α
First release: 18 February 2018
www.sciencemag.org
(Page numbers not final at time of first release)
4

β
β
α
First release: 18 February 2018
www.sciencemag.org
(Page numbers not final at time of first release)
5

β
First release: 18 February 2018
www.sciencemag.org
(Page numbers not final at time of first release)
6

First release: 18 February 2018
www.sciencemag.org
(Page numbers not final at time of first release)
7

First release: 18 February 2018
www.sciencemag.org
(Page numbers not final at time of first release)
8

⋅
First release: 18 February 2018
www.sciencemag.org
(Page numbers not final at time of first release)
9

First release: 18 February 2018
www.sciencemag.org
(Page numbers not final at time of first release) 10

First release: 18 February 2018
www.sciencemag.org
(Page numbers not final at time of first release) 11

Modular radical cross-coupling with sulfones enables access to sp3-rich (fluoro)alkylated
scaffolds
Rohan R. Merchant, Jacob T. Edwards, Tian Qin, Monika M. Kruszyk, Cheng Bi, Guanda Che, Deng-Hui Bao, Wenhua Qiao, Lijie
Sun, Michael R. Collins, Olugbeminiyi O. Fadeyi, Gary M. Gallego, James J. Mousseau, Philippe Nuhant and Phil S. Baran
published online February 18, 2018
ARTICLE TOOLS
http://science.sciencemag.org/content/early/2018/02/16/science.aar7335
SUPPLEMENTARY
MATERIALS
http://science.sciencemag.org/content/suppl/2018/02/16/science.aar7335.DC1
REFERENCES
This article cites 71 articles, 3 of which you can access for free
http://science.sciencemag.org/content/early/2018/02/16/science.aar7335#BIBL
PERMISSIONS
http://www.sciencemag.org/help/reprints-and-permissions
Use of this article is subject to the Terms of Service
Science (print ISSN 0036-8075; online ISSN 1095-9203) is published by the American Association for the Advancement of
Science, 1200 New York Avenue NW, Washington, DC 20005. 2017 © The Authors, some rights reserved; exclusive licensee
American Association for the Advancement of Science. No claim to original U.S. Government Works. The title Science is a
registered trademark of AAAS.