Epimerization of Tertiary Carbon Centers via Reversible Radical Cleavage of Unactivated C(sp3)-H Bonds

Yaxin Wang, Xiafei Hu, Cristian A. Morales-Rivera, Guo Xing Li, Xin Huang, Gang He, Peng Liu, Gong Chen

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Reversible cleavage of C(sp3)-H bonds can enable racemization or epimerization, offering a valuable tool to edit the stereochemistry of organic compounds. While epimerization reactions operating via cleavage of acidic C(sp3)-H bonds, such as the Cα-H of carbonyl compounds, have been widely used in organic synthesis and enzyme-catalyzed biosynthesis, epimerization of tertiary carbons bearing a nonacidic C(sp3)-H bond is much more challenging with few practical methods available. Herein, we report the first synthetically useful protocol for the epimerization of tertiary carbons via reversible radical cleavage of unactivated C(sp3)-H bonds with hypervalent iodine reagent benziodoxole azide and H2O under mild conditions. These reactions exhibit excellent reactivity and selectivity for unactivated 3° C-H bonds of various cycloalkanes and offer a powerful strategy for editing the stereochemical configurations of carbon scaffolds intractable to conventional methods. Mechanistic study suggests that the unique ability of N3 to serve as a catalytic H atom shuttle is critical to reversibly break and reform 3° C-H bonds with high efficiency and selectivity.

Original languageEnglish (US)
Pages (from-to)9678-9684
Number of pages7
JournalJournal of the American Chemical Society
Volume140
Issue number30
DOIs
StatePublished - Aug 1 2018

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Carbon
Bearings (structural)
Cycloparaffins
Synthetic Chemistry Techniques
Carbonyl compounds
Stereochemistry
Azides
Biosynthesis
Iodine
Organic compounds
Scaffolds
Enzymes
Atoms
2-iodoxybenzoic acid

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Wang, Yaxin ; Hu, Xiafei ; Morales-Rivera, Cristian A. ; Li, Guo Xing ; Huang, Xin ; He, Gang ; Liu, Peng ; Chen, Gong. / Epimerization of Tertiary Carbon Centers via Reversible Radical Cleavage of Unactivated C(sp3)-H Bonds. In: Journal of the American Chemical Society. 2018 ; Vol. 140, No. 30. pp. 9678-9684.
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Wang, Y, Hu, X, Morales-Rivera, CA, Li, GX, Huang, X, He, G, Liu, P & Chen, G 2018, 'Epimerization of Tertiary Carbon Centers via Reversible Radical Cleavage of Unactivated C(sp3)-H Bonds', Journal of the American Chemical Society, vol. 140, no. 30, pp. 9678-9684. https://doi.org/10.1021/jacs.8b05753

Epimerization of Tertiary Carbon Centers via Reversible Radical Cleavage of Unactivated C(sp3)-H Bonds. / Wang, Yaxin; Hu, Xiafei; Morales-Rivera, Cristian A.; Li, Guo Xing; Huang, Xin; He, Gang; Liu, Peng; Chen, Gong.

In: Journal of the American Chemical Society, Vol. 140, No. 30, 01.08.2018, p. 9678-9684.

Research output: Contribution to journalArticle

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AU - Wang, Yaxin

AU - Hu, Xiafei

AU - Morales-Rivera, Cristian A.

AU - Li, Guo Xing

AU - Huang, Xin

AU - He, Gang

AU - Liu, Peng

AU - Chen, Gong

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