Metallaphotoredox-Catalyzed Cross-Electrophile C sp 3 -C sp 3 Coupling of Aliphatic Bromides

Russell T. Smith, Xiaheng Zhang, Juan A. Rincón, Javier Agejas, Carlos Mateos, Mario Barberis, Susana García-Cerrada, Oscar De Frutos, David W.C. Macmillan

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Abstract

A strategy for the installation of small alkyl fragments onto pharmaceutically relevant aliphatic structures has been established via metallaphotoredox catalysis. Herein, we report that tris(trimethylsilyl)silanol can be employed as an effective halogen abstraction reagent that, in combination with photoredox and nickel catalysis, allows a generic approach to C sp 3 -C sp 3 cross-electrophile coupling. In this study, we demonstrate that a variety of aliphatic drug-like groups can be successfully coupled with a number of commercially available small alkyl electrophiles, including methyl tosylate and strained cyclic alkyl bromides. Moreover, the union of two secondary aliphatic carbon centers, a long-standing challenge for organic molecule construction, has been accomplished with a wide array of structural formats. Last, this technology can be selectively merged with C sp 2 -C sp 3 aryl-alkyl couplings to build drug-like systems in a highly modular fashion.

Original languageEnglish (US)
Pages (from-to)17433-17438
Number of pages6
JournalJournal of the American Chemical Society
Volume140
Issue number50
DOIs
StatePublished - Dec 19 2018

All Science Journal Classification (ASJC) codes

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

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    Smith, R. T., Zhang, X., Rincón, J. A., Agejas, J., Mateos, C., Barberis, M., García-Cerrada, S., De Frutos, O., & Macmillan, D. W. C. (2018). Metallaphotoredox-Catalyzed Cross-Electrophile C sp 3 -C sp 3 Coupling of Aliphatic Bromides Journal of the American Chemical Society, 140(50), 17433-17438. https://doi.org/10.1021/jacs.8b12025