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, Phil S. Baran

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)75-80
Number of pages6
JournalScience
Volume360
Issue number6384
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

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Sulfones
Carbon
Agrochemicals
Poisons
Halogenation
Nickel
Zinc
Electrons

ASJC Scopus subject areas

  • General

Cite this

Merchant, R. R., Edwards, J. T., Qin, T., Kruszyk, M. M., Bi, C., Che, G., ... Baran, P. S. (2018). Modular radical cross-coupling with sulfones enables access to sp3-rich (fluoro)alkylated scaffolds. Science, 360(6384), 75-80. https://doi.org/10.1126/science.aar7335

Modular radical cross-coupling with sulfones enables access to sp3-rich (fluoro)alkylated scaffolds. / Merchant, Rohan R.; Edwards, Jacob T.; Qin, Tian; Kruszyk, Monika M.; Bi, Cheng; Che, Guanda; Bao, Deng Hui; Qiao, Wenhua; Sun, Lijie; Collins, Michael R.; Fadeyi, Olugbeminiyi O.; Gallego, Gary M.; Mousseau, James J.; Nuhant, Philippe; Baran, Phil S.

In: Science, Vol. 360, No. 6384, 01.01.2018, p. 75-80.

Research output: Contribution to journalArticle

Merchant, RR, Edwards, JT, Qin, T, Kruszyk, MM, Bi, C, Che, G, Bao, DH, Qiao, W, Sun, L, Collins, MR, Fadeyi, OO, Gallego, GM, Mousseau, JJ, Nuhant, P & Baran, PS 2018, 'Modular radical cross-coupling with sulfones enables access to sp3-rich (fluoro)alkylated scaffolds', Science, vol. 360, no. 6384, pp. 75-80. https://doi.org/10.1126/science.aar7335
Merchant, Rohan R. ; Edwards, Jacob T. ; Qin, Tian ; Kruszyk, Monika M. ; Bi, Cheng ; Che, Guanda ; Bao, Deng Hui ; Qiao, Wenhua ; Sun, Lijie ; Collins, Michael R. ; Fadeyi, Olugbeminiyi O. ; Gallego, Gary M. ; Mousseau, James J. ; Nuhant, Philippe ; Baran, Phil S. / Modular radical cross-coupling with sulfones enables access to sp3-rich (fluoro)alkylated scaffolds. In: Science. 2018 ; Vol. 360, No. 6384. pp. 75-80.
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