Issue 5, 2017

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

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

Supplementary files

Article information

Article type
Edge Article
Submitted
19 jan 2017
Accepted
24 feb 2017
First published
06 mar 2017
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2017,8, 3512-3522

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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