Asymmetric allylic substitution-isomerization to axially chiral enamides via hydrogen-bonding assisted central-to-axial chirality transfer.

Chemical Science
Chao SunYing He

Abstract

Axially chiral enamides bearing a N-C axis have been recently studied and were proposed to be valuable chiral building blocks, but a stereoselective synthesis has not been achieved. Here, we report the first enantioselective synthesis of axially chiral enamides via a highly efficient, catalytic approach. In this approach, C(sp2)-N bond formation is achieved through an iridium-catalyzed asymmetric allylation, and then in situ isomerization of the initial products through an organic base promoted 1,3-H transfer, leading to the enamide products with excellent central-to-axial transfer of chirality. Computational and experimental studies revealed that the 1,3-H transfer occurs via a stepwise deprotonation/re-protonation pathway with a chiral ion-pair intermediate. Hydrogen bonding interactions with the enamide carbonyl play a significant role in promoting both the reactivity and stereospecificity of the stepwise 1,3-H transfer. The mild and operationally simple formal N-vinylation reaction delivered a series of configurationally stable axially chiral enamides with good to excellent yields and enantioselectivities.

References

Feb 3, 2007·Natural Product Reports·Joseph P Michael
May 21, 2010·Journal of the American Chemical Society·Yutaka SagaMasakatsu Shibasaki
Aug 27, 2010·FEMS Microbiology Reviews·Stephan HeebMiguel Cámara
Sep 30, 2010·Accounts of Chemical Research·John F Hartwig, Levi M Stanley
Jul 20, 2011·Journal of the American Chemical Society·Yongwei WuLi Deng
Aug 13, 2011·Chemical Reviews·Vellaisamy SridharanJ Carlos Menéndez
Jan 3, 2012·Journal of the American Chemical Society·Seiji ShirakawaKeiji Maruoka
Mar 13, 2012·Organic & Biomolecular Chemistry·Paolo TosattiStephen P Marsden
Aug 22, 2012·Journal of the American Chemical Society·Yongwei Wu, Li Deng
Jun 6, 2014·Chemical Communications : Chem Comm·Evgeny LarionovClément Mazet
Jun 13, 2014·Angewandte Chemie·Rebecca L DavisKarl Anker Jørgensen
Jul 10, 2014·Journal of the American Chemical Society·Nicola Di IorioGiorgio Bencivenni
Sep 17, 2016·Journal of the American Chemical Society·Samuel Martinez-ErroBelén Martín-Matute
May 4, 2017·Nature Communications·Sheng-Cai ZhengBin Tan
Sep 25, 2017·Accounts of Chemical Research·Jianping Qu, Günter Helmchen
May 22, 2018·Journal of the American Chemical Society·Shiqi JiaHailong Yan
Oct 20, 2018·Journal of the American Chemical Society·David M H AscoughRobert S Paton
Nov 23, 2018·Journal of the American Chemical Society·Yu TanHailong Yan
Dec 26, 2018·Chemical Reviews·Qiang ChengShu-Li You
May 14, 2019·Angewandte Chemie·Xi-Jia LiuShu-Li You
Jun 28, 2019·Accounts of Chemical Research·Simon L RösslerErick M Carreira

❮ 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.