@article{e5d38f84605a47c9bd7eeb51bfc131ec,
title = "Modular radical cross-coupling with sulfones enables access to sp3-rich (fluoro)alkylated scaffolds",
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.",
author = "Merchant, {Rohan R.} and Edwards, {Jacob T.} and Tian Qin and Kruszyk, {Monika M.} and Cheng Bi and Guanda Che and Bao, {Deng Hui} and Wenhua Qiao and Lijie Sun and Collins, {Michael R.} and Fadeyi, {Olugbeminiyi O.} and Gallego, {Gary M.} and Mousseau, {James J.} and Philippe Nuhant and Baran, {Phil S.}",
note = "Funding Information: We thank D.-H. Huang and L. Pasternack (TSRI) for assistance with NMR spectroscopy; J. Chen (TSRI Automated Synthesis Facility); A. Rheingold, C. E. Moore, and M. A. Galella (University of California, San Diego) for x-ray crystallographic analysis; J. J. Sabatini (U.S. Army Research Laboratory) for friction sensitivity testing of compounds 8 and 9; and J. E. Spangler (Pfizer) and E.-X. Zhang (Asymchem) for helpful discussions. Funding: Financial support for this work was provided by Pfizer and the National Institutes of Health (grant GM-118176). Vividion Therapeutics supported a predoctoral fellowship to R.R.M., the U.S. Department of Defense supported a predoctoral fellowship to J.T.E. (National Defense Science and Engineering Graduate Fellowship Program), the Innovation Fund Denmark supported a predoctoral fellowship to M.M.K. (grant 4135-00085B), and Nankai University supported C.B. Author contributions: R.R.M., J.T.E., T.Q., and P.S.B. conceived the work. R.R.M., J.T.E., T.Q., M.M.K., C.B., and P.S.B. designed the experiments and analyzed the data. R.R.M., J.T.E., T.Q., M.M.K., C.B., M.R.C., O.O.F., G.M.G., J.J.M., and P.N. performed the experiments. G.C., D.-H.B., W.Q., and L.S. performed molescale experiments. P.S.B. wrote the manuscript. R.R.M., J.T.E., and T.Q. assisted in writing and editing the manuscript. Competing interests: Authors declare no competing interests. Data and materials availability: Experimental procedures, frequently asked questions, optimization data, 1H NMR spectra, 13C NMR spectra, and mass spectrometry data are available in the supplementary materials. Crystallographic data are available free of charge from the Cambridge Crystallographic Data Centre under reference numbers CCDC 1590142-1590144, 1819895, and 1819896.",
year = "2018",
doi = "10.1126/science.aar7335",
language = "English (US)",
volume = "360",
pages = "75--80",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6384",
}