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

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

University of Bonn

Research output: Contribution to journal › Article › peer-review

52 Scopus citations

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 sp³ C-H bond activation allowing for an sp³-sp³ 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.

Original language	English
Pages (from-to)	3982-3985
Number of pages	4
Journal	Organic Letters
Volume	17
Issue number	16
DOIs	https://doi.org/10.1021/acs.orglett.5b01845
State	Published - 2 Jul 2015
Externally published	Yes

Access to Document

10.1021/acs.orglett.5b01845

Cite this

@article{dae6ad3e5f964804bc7cf373b18010de,

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

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 sp3 C-H bond activation allowing for an sp3-sp3 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.",

author = "Tongtong Wang and Michael Schrempp and Andreas Berndh{\"a}user and Olav Schiemann and Dirk Menche",

note = "Publisher Copyright: {\textcopyright} 2015 American Chemical Society.",

year = "2015",

month = jul,

day = "2",

doi = "10.1021/acs.orglett.5b01845",

language = "English",

volume = "17",

pages = "3982--3985",

journal = "Organic Letters",

issn = "1523-7060",

publisher = "American Chemical Society",

number = "16",

}

TY - JOUR

T1 - Efficient and General Aerobic Oxidative Cross-Coupling of THIQs with Organozinc Reagents Catalyzed by CuCl2

T2 - Proof of a Radical Intermediate

AU - Wang, Tongtong

AU - Schrempp, Michael

AU - Berndhäuser, Andreas

AU - Schiemann, Olav

AU - Menche, Dirk

PY - 2015/7/2

Y1 - 2015/7/2

N2 - 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 sp3 C-H bond activation allowing for an sp3-sp3 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.

AB - 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 sp3 C-H bond activation allowing for an sp3-sp3 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.

UR - http://www.scopus.com/inward/record.url?scp=84939811085&partnerID=8YFLogxK

U2 - 10.1021/acs.orglett.5b01845

DO - 10.1021/acs.orglett.5b01845

M3 - Article

AN - SCOPUS:84939811085

SN - 1523-7060

VL - 17

SP - 3982

EP - 3985

JO - Organic Letters

JF - Organic Letters

IS - 16

ER -

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

Abstract

Access to Document

Other files and links

Fingerprint

Cite this