Visible-Light-Driven Palladium-Catalyzed Radical Alkylation of C-H Bonds with Unactivated Alkyl Bromides

Angew Chem Int Ed Engl. 2017 Dec 4;56(49):15683-15687. doi: 10.1002/anie.201704513. Epub 2017 Nov 8.

Abstract

Reported herein is a novel visible-light photoredox system with Pd(PPh3 )4 as the sole catalyst for the realization of the first direct cross-coupling of C(sp3 )-H bonds in N-aryl tetrahydroisoquinolines with unactivated alkyl bromides. Moreover, intra- and intermolecular alkylations of heteroarenes were also developed under mild reaction conditions. A variety of tertiary, secondary, and primary alkyl bromides undergo reaction to generate C(sp3 )-C(sp3 ) and C(sp2 )-C(sp3 ) bonds in moderate to excellent yields. These redox-neutral reactions feature broad substrate scope (>60 examples), good functional-group tolerance, and facile generation of quaternary centers. Mechanistic studies indicate that the simple palladium complex acts as the visible-light photocatalyst and radicals are involved in the process.

Keywords: cross-coupling; halides; palladium; photochemistry; radicals.

Publication types

  • Research Support, Non-U.S. Gov't