Metal-free C–H alkylation of heteroarenes with alkyltrifluoroborates: a general protocol for 1°, 2° and 3° alkylation† †Electronic supplementary information (ESI) available: Experimental details and spectral data. See DOI: 10.1039/c7sc00283a Click here for additional data file

• Published in: Chemical science (Cambridge) Vol. 8; no. 5; pp. 3512 - 3522
• Main Authors: Matsui, Jennifer K., Primer, David N., Molander, Gary A.
• Format: Journal Article
• Language: English
• Published: Royal Society of Chemistry 06.03.2017
• Subjects: Chemistry
• DOI: 10.1039/c7sc00283a
• ISSN: 2041-6520

A photoredox-catalyzed C–H functionalization of heteroarenes using a variety of primary, secondary, and tertiary alkyltrifluoroborates is reported. 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 1 H and 13 C NMR a distinct heteroaryl species was observed in the presence of acid catalyst and BF 3 .