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. 2018 Jan 22;9(8):2295-2300.
doi: 10.1039/c7sc04900e. eCollection 2018 Feb 28.

Oxidative β-C-H sulfonylation of cyclic amines

R J Griffiths  1   2 , W C Kong  1   3 , S A Richards  1 , G A Burley  2 , M C Willis  3 , E P A Talbot  1
Affiliations

Oxidative β-C-H sulfonylation of cyclic amines

R J Griffiths et al. Chem Sci. .

Abstract

A transition metal-free strategy for the dehydrogenative β-sulfonylation of tertiary cyclic amines is described. N-Iodosuccinimide facilitates regioselective oxidative sulfonylation at C-H bonds positioned β to the nitrogen atom of tertiary amines, installing enaminyl sulfone functionality in cyclic systems. Mild reaction conditions, broad functional group tolerance and a wide substrate scope are demonstrated. The nucleophilic character of the enaminyl sulfone is harnessed, demonstrating potential application for scaffold diversification.

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Figures

Scheme 1
Scheme 1. (a) The C–H functionalization of piperidines, and (b) this work: the preparation cyclic enaminyl sulfones.
Scheme 2
Scheme 2. Radical-clock experiment with 3p, indicating that the reaction does not proceed via a radical-based mechanism. Isolated yields shown; values in parentheses show conversion to product as measured by 1H NMR analysis of crude product mixture using an internal standard. Tol = para-tolyl.
Scheme 3
Scheme 3. Cyclic enaminyl sulfones as templates for synthesis. Tol = para-tolyl.
See this image and copyright information in PMC

References

    1. Vitaku E., Smith D. T., Njardarson J. T. J. Med. Chem. 2014;57:10257–10274. - PubMed
    2. Petukhov P. A., Zhang J., Wang C. Z., Ye Y. P., Johnson K. M., Kozikowski A. P. J. Med. Chem. 2004;47:3009–3018. - PubMed
    3. Nakanishi M., Tashiro C., Munakata T., Araki K., Tsumagari T., Imamura H. J. Med. Chem. 1970;13:644–648. - PubMed
    4. Pati B., Banerjee S. J. Pharma Res. 2012;5:5493–5509.
    1. Cernak T., Dykstra K. D., Tyagarajan S., Vachal P., Krska S. W. Chem. Soc. Rev. 2016;45:546–576. - PubMed
    1. Spangler J. E., Kobayashi Y., Verma P., Wang D.-H., Yu J.-Q. J. Am. Chem. Soc. 2015;137:11876–11879. - PMC - PubMed
    2. Pastine S. J., Gribkov D. V., Sames D. J. Am. Chem. Soc. 2006;128:14220–14221. - PubMed
    3. He J., Hamann L. G., Davies H. M. L., Beckwith R. E. J. Nat. Commun. 2015;6:5943–5951. - PubMed
    4. Shi L., Xia W. Chem. Soc. Rev. 2012;41:7687. - PubMed
    5. Mitchell E. A., Peschiulli A., Lefevre N., Meerpoel L., Maes B. U. W. Chem.–Eur. J. 2012;18:10092–10142. - PubMed
    1. Topczewski J. J., Cabrera P. J., Saper N. I., Sanford M. S. Nature. 2016;531:220–224. - PMC - PubMed
    2. Affron D. P., Davis O. A., Bull J. A. Org. Lett. 2014;16:4956–4959. - PubMed
    3. Asensio G., Gonzalez-Nunez M. E., Bernardini C. B., Mello R., Adam W. J. Am. Chem. Soc. 1993;115:7250–7253.
    4. Lee M., Sanford M. S. J. Am. Chem. Soc. 2015;137:12796–12799. - PMC - PubMed
    5. Takasu N., Oisaki K., Kanai M. Org. Lett. 2013;15:1918–1921. - PubMed
    6. Chen W., Kang Y., Wilde R. G., Seidel D. Angew. Chem., Int. Ed. 2014;53:5179–5182. - PMC - PubMed
    7. Ma L., Paul A., Breugst M., Seidel D. Chem.–Eur. J. 2016;22:18179–18189. - PMC - PubMed
    8. Howell J. M., Feng K., Clark J. R., Trzepkowski L. J., White M. C. J. Am. Chem. Soc. 2015;137:14590–14593. - PMC - PubMed
    9. Schultz D. M., Lévesque F., DiRocco D. A., Reibarkh M., Ji Y., Joyce L. A., Dropinski J. F., Sheng H., Sherry B. D., Davies I. W. Angew. Chem., Int. Ed. 2017;56:15274–15278. - PubMed
    1. Fromm E., Wittmann J. Ber. Dtsch. Chem. Ges. 1908;41:2264–2273.
    2. Tucker H., Crook J. W., Chesterson G. J. J. Med. Chem. 1988;31:954–959. - PubMed
    3. Couderchet M., Schmalfuß J., Böger P. Pestic. Sci. 1998;52:381–387.
    4. Smithkline Beecham Corporation, Busch-Petersen J. and Glaxosmithkline Llc, Ca. Pat., CA2650009 C, 2014.
    5. Vertex Pharmaceuticals Incorporated, US Pat., US2013/115310, 2013.
    6. Bristol-Myers Squibb Company, WO2015/103510, 2015.