Copper-catalyzed oxidative benzylic C-H cyclization via iminyl radical from intermolecular anion-radical redox relay

Nature Communications
Xiang-Huan ShanYan-Biao Kang

Abstract

Base-promoted C-H cleavage without transition metals opens a practical alternative for the one based on noble metals or radical initiators. The resulting carbanion can pass through radical addition to unsaturated bonds like C-N or C-C triple bonds, in which stoichiometric oxidants are needed. When in situ C-H cleavage meets catalytic carbanion-radical relay, it turns to be challenging but has not been accomplished yet. Here we report the combination of base-promoted benzylic C-H cleavage and copper-catalyzed carbanion-radical redox relay. Catalytic amount of naturally abundant and inexpensive copper salt, such as copper(II) sulfate, is used for anion-radical redox relay without any external oxidant. By avoiding using N-O/N-N homolysis or radical initiators to generate iminyl radicals, this strategy realizes modular synthesis of N-H indoles and analogs from abundant feedstocks, such as toluene and nitrile derivatives, and also enables rapid synthesis of large scale pharmaceuticals.

References

Dec 4, 1998·Journal of Medicinal Chemistry·R GastparE von Angerer
Dec 9, 2004·Angewandte Chemie·Phil S BaranBenjamin D Hafensteiner
Jun 29, 2006·Journal of the American Chemical Society·Phil S BaranJohn D Gallagher
Jul 14, 2006·Chemical Reviews·Guy R Humphrey, Jeffrey T Kuethe
Sep 30, 2006·Angewandte Chemie·Phil S Baran, Michael P DeMartino
Dec 13, 2006·Angewandte Chemie·Aurore ServaisMax Malacria
Feb 8, 2007·Angewandte Chemie·Barry M Trost, Andrew McClory
May 26, 2007·Journal of the American Chemical Society·Benjamin J StokesTom G Driver
Aug 15, 2008·Angewandte Chemie·Sebastian WürtzFrank Glorius
Sep 11, 2008·ChemMedChem·Valentina AssoMarco Macchia
Sep 19, 2008·Journal of the American Chemical Society·Sun-Liang CuiYan-Guang Wang
Feb 28, 2009·Journal of the American Chemical Society·José BarluengaCarlos Valdés
Jun 26, 2009·Journal of the American Chemical Society·David R StuartKeith Fagnou
Mar 9, 2010·Journal of the American Chemical Society·Marie-Hélène LarraufieLouis Fensterbank
Dec 15, 2010·Journal of the American Chemical Society·Fenghai GuoRegan J Thomson
May 12, 2011·Chemical Reviews·Sandro Cacchi, Giancarlo Fabrizi
Mar 7, 2012·Chemical Reviews·Morteza Shiri
May 23, 2012·Journal of the American Chemical Society·Ye WeiNaohiko Yoshikai
May 16, 2013·Journal of the American Chemical Society·Chun-Xiang ZhuoShu-Li You
Oct 10, 2013·Journal of the American Chemical Society·Baoqing LiuJin Zhu
Jun 4, 2014·Angewandte Chemie·Laura FraKilian Muñiz
Sep 23, 2011·Tetrahedron·Douglass F Taber, Pavan K Tirunahari
Apr 20, 2016·Journal of the American Chemical Society·Lin HuangShu-Li You
May 24, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·John C Walton
Jun 22, 2016·Journal of the American Chemical Society·Jacob DaviesDaniele Leonori
Nov 29, 2016·Chemical Communications : Chem Comm·Chuanhua QuChengjian Zhu
Dec 23, 2016·Journal of the American Chemical Society·Laurean IliesEiichi Nakamura
May 26, 2017·Journal of the American Chemical Society·Takuma WatanabeShinichi Saito
Jun 18, 2017·Organic & Biomolecular Chemistry·Fu-Xiang WangShi-Kai Tian
Dec 28, 2017·Angewandte Chemie·Dan-Dan ZhaiBing-Tao Guan
Feb 3, 2018·Angewandte Chemie·Yu-Feng LiuBing-Tao Guan
Apr 17, 2018·Angewandte Chemie·Yasuhiro YamashitaShū Kobayashi
Aug 24, 2018·Nature Communications·Zhiting WangPatrick J Walsh

❮ Previous
Next ❯

Citations

May 8, 2019·Angewandte Chemie·Jianyou MaoPatrick J Walsh
Mar 13, 2020·Chemical Communications : Chem Comm·Xiang-Huan ShanYan-Biao Kang
Jul 28, 2021·The Journal of Organic Chemistry·Ke-Wei ChenFeng Shi
May 22, 2020·Organic Letters·Ya-Wei LiYan-Biao Kang

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.