Efficient and General Aerobic Oxidative Cross-Coupling of THIQs with Organozinc Reagents Catalyzed by CuCl2: Proof of a Radical Intermediate

Tongtong Wang; Michael Schrempp; Andreas Berndhäuser; Olav Schiemann; Dirk Menche

doi:10.1021/acs.orglett.5b01845

Efficient and General Aerobic Oxidative Cross-Coupling of THIQs with Organozinc Reagents Catalyzed by CuCl2: Proof of a Radical Intermediate

Org Lett. 2015 Aug 21;17(16):3982-5. doi: 10.1021/acs.orglett.5b01845. Epub 2015 Aug 7.

Authors

Tongtong Wang¹, Michael Schrempp¹, Andreas Berndhäuser², Olav Schiemann², Dirk Menche¹

Affiliations

¹ †Kekulé-Intitute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Strasse 1, D-53121 Bonn, Germany.
² ‡Institute of Physical and Theoretical Chemistry, University of Bonn, Wegelerstrasse 12, D-53115 Bonn, Germany.

PMID: 26252357
DOI: 10.1021/acs.orglett.5b01845

Abstract

A general new method for the highly concise synthesis of C-1-alkylated tetrahydroisoquinolines (THIQ) is reported. The CuCl2-catalyzed procedure is based on a coupling of nonfunctionalized THIQs with organozinc reagents under aerobic conditions. It proceeds in high yields and is broadly applicable to a wide range of substrates. It relies on a regioselective sp(3) C-H bond activation allowing for an sp(3)-sp(3) bond union under mild reaction conditions in a rapid and effective manner. Mechanistically it involves an iminium ion intermediate that is formed via an organic radical involving a single-electron-transfer process. For the first time for this type of reaction a radical intermediate has been proven by EPR spectroscopy.