Palladium and Lewis-Acid-Catalyzed Intramolecular Aminocyanation of Alkenes: Scope, Mechanism, and Stereoselective Alkene Difunctionalizations

Journal of the American Chemical Society
Zhongda PanChristopher J Douglas

Abstract

An expansion of methodologies aimed at the formation of versatile organonitriles, via the intramolecular aminocyanation of unactivated alkenes, is herein reported. Importantly, the need for a rigid tether in these reactions has been obviated. The ease-of-synthesis and viability of substrates bearing flexible backbones has permitted for diastereoselective variants as well. We demonstrated the utility of this methodology with the formation of pyrrolidones, piperidinones, isoindolinones, and sultams. Furthermore, subsequent transformation of these motifs into medicinally relevant molecules is also demonstrated. A double crossover 13C-labeling experiment is consistent with a fully intramolecular cyclization mechanism. Deuterium labeling experiments support a mechanism involving syn-addition across the alkene.

References

Jan 5, 1999·Bioorganic & Medicinal Chemistry Letters·T R BelliottiL D Wise
Nov 21, 2001·Accounts of Chemical Research·P C KamerJ N Reek
Dec 26, 2001·Chemical Reviews·P W van LeeuwenP Dierkes
Jun 6, 2003·Journal of the American Chemical Society·Michinori SuginomeMasahiro Murakami
Dec 7, 2007·Chemical & Pharmaceutical Bulletin·Norimasa KanamitsuManabu Soga
Dec 14, 2007·Journal of the American Chemical Society·Guillaume Barbe, André B Charette
Aug 5, 2009·The Journal of Organic Chemistry·Danielle M NortonMichael C Baird
Apr 3, 2012·Journal of the American Chemical Society·Dennis C KoesterYoshiaki Nakao
Nov 8, 2012·Angewandte Chemie·Jinho KimSukbok Chang
Jan 29, 2013·Angewandte Chemie·Hongwei ZhangQian Zhang
Mar 4, 2014·Journal of the American Chemical Society·Yosuke MiyazakiYoshiaki Nakao
Apr 11, 2014·Angewandte Chemie·Zhongda PanChristopher J Douglas
Jul 2, 2014·Chemical Communications : Chem Comm·Naveen R RondlaChristopher J Douglas

❮ Previous
Next ❯

Citations

Sep 14, 2018·Organic & Biomolecular Chemistry·Manthena Chaitanya, Pazhamalai Anbarasan
Jan 23, 2019·Organic & Biomolecular Chemistry·Joseph Becica, Graham E Dobereiner
Jul 17, 2019·Angewandte Chemie·Feiyang XuDonald A Watson
Mar 19, 2021·Organic & Biomolecular Chemistry·Ziying WuHuanfeng Jiang
May 10, 2020·Organic Letters·Yungeun Kwon, Qiu Wang
Jun 12, 2019·Chemical Reviews·Katerina M Korch, Donald A Watson
Sep 5, 2018·The Journal of Organic Chemistry·Nicholas W M MichelSophie A L Rousseaux

❮ Previous
Next ❯

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.