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Issue 5, 2017
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Metal-free C–H alkylation of heteroarenes with alkyltrifluoroborates: a general protocol for 1°, 2° and 3° alkylation

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Abstract

A photoredox-catalyzed C–H functionalization of heteroarenes using a variety of primary, secondary, and tertiary alkyltrifluoroborates is reported. Using Fukuzumi's organophotocatalyst and a mild oxidant, conditions amenable for functionalizing complex heteroaromatics are described, providing a valuable tool for late-stage derivatization. The reported method addresses the three major limitations of previously reported photoredox-mediated Minisci reactions: (1) use of superstoichiometric amounts of a radical precursor, (2) capricious regioselectivity, and (3) incorporation of expensive photocatalysts. Additionally, a number of unprecedented, complex alkyl radicals are used, thereby increasing the chemical space accessible to Minisci chemistry. To showcase the application in late-stage functionalization, quinine and camptothecin analogues were synthesized. Finally, NMR studies were conducted to provide a rationalization for the heteroaryl activation that permits the use of a single equivalent of radical precursor and also leads to enhanced regioselectivity. Thus, by 1H and 13C NMR a distinct heteroaryl species was observed in the presence of acid catalyst and BF3.

Graphical abstract: Metal-free C–H alkylation of heteroarenes with alkyltrifluoroborates: a general protocol for 1°, 2° and 3° alkylation

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Publication details

The article was received on 19 Jan 2017, accepted on 24 Feb 2017 and first published on 06 Mar 2017


Article type: Edge Article
DOI: 10.1039/C7SC00283A
Citation: Chem. Sci., 2017,8, 3512-3522
  • Open access: Creative Commons BY-NC license
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    Metal-free C–H alkylation of heteroarenes with alkyltrifluoroborates: a general protocol for 1°, 2° and 3° alkylation

    J. K. Matsui, D. N. Primer and G. A. Molander, Chem. Sci., 2017, 8, 3512
    DOI: 10.1039/C7SC00283A

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