Enantioselective desymmetrization of prochiral cyclohexanones by organocatalytic intramolecular Michael additions to α,β-unsaturated esters.

Angewandte Chemie
Adam D Gammack YamagataDarren J Dixon

Abstract

A new catalytic asymmetric desymmetrization reaction for the synthesis of enantioenriched derivatives of 2-azabicyclo[3.3.1]nonane, a key motif common to many alkaloids, has been developed. Employing a cyclohexanediamine-derived primary amine organocatalyst, a range of prochiral cyclohexanone derivatives possessing an α,β-unsaturated ester moiety linked to the 4-position afforded the bicyclic products, which possess three stereogenic centers, as single diastereoisomers in high enantioselectivity (83-99% ee) and in good yields (60-90%). Calculations revealed that stepwise C-C bond formation and proton transfer via a chair-shaped transition state dictate the exclusive endo selectivity and enabled the development of a highly enantioselective primary amine catalyst.

References

Jul 30, 2004·Organic Letters·Toshiyuki KanTohru Fukuyama
May 12, 2005·Chemical Reviews·Michael E Jung, Grazia Piizzi
Nov 17, 2005·Journal of the American Chemical Society·Yujiro HayashiMitsuru Shoji
Feb 24, 2006·Chemical Communications : Chem Comm·Yongmei Xu, Armando Córdova
Mar 4, 2006·Chemistry : a European Journal·Stephen J Connon
Mar 22, 2006·Chemical Communications : Chem Comm·Svetlana B Tsogoeva, Shengwei Wei
Jun 1, 2006·Journal of the American Chemical Society·Hongbing Huang, Eric N Jacobsen
Dec 13, 2007·Chemical Reviews·Santanu MukherjeeBenjamin List
Dec 18, 2007·Journal of the American Chemical Society·Ngoc T VoMatthew J Gaunt
Jan 12, 2008·Accounts of Chemical Research·Yan Zhao, Donald G Truhlar
Mar 26, 2009·Chemical Communications : Chem Comm·Li-Wen XuYixin Lu
Aug 7, 2009·Angewandte Chemie·Gustav DickmeissKarl Anker Jørgensen
Mar 9, 2010·Journal of the American Chemical Society·Qing GuShu-Li You
May 17, 2011·Journal of the American Chemical Society·Jordi BurésDonna G Blackmond
Mar 29, 2012·Journal of the American Chemical Society·Jordi BurésDonna G Blackmond
May 1, 2013·Organic Letters·Ben BradshawJosep Bonjoch
Jul 25, 2013·Nature Chemistry·Zhaoyong LuAng Li
Sep 24, 2013·Organic & Biomolecular Chemistry·Olga V SerdyukSvetlana B Tsogoeva
Mar 7, 2014·Natural Product Reports·Baldip KangDarren J Dixon
May 7, 2014·Angewandte Chemie·Roberto BalletteJoan Bosch
Jun 27, 2014·Journal of the American Chemical Society·Yu-hong Lam, K N Houk
Jan 12, 2010·Journal of Chemical Theory and Computation·Martin KorthPavel Hobza

❮ Previous
Next ❯

Citations

Apr 15, 2016·Journal of the American Chemical Society·Ren-Rong LiuYi-Xia Jia
Mar 31, 2017·Organic Letters·Adam D Gammack Yamagata, Darren J Dixon
Oct 6, 2015·Chemical Communications : Chem Comm·Shivakrishna KallepuRambabu Chegondi
Oct 10, 2018·Chemistry, an Asian Journal·Maddalen AgirreFernando P Cossío
Jun 25, 2016·Beilstein Journal of Organic Chemistry·Giorgos KoutoulogenisChristoforos G Kokotos
Jan 24, 2020·Organic & Biomolecular Chemistry·Weigang HeWeiqing Xie
Jun 28, 2016·Chemical Society Reviews·A BorissovD J Dixon
Jun 8, 2021·Chemical Science·Benjamin D A ShennanDarren J Dixon
Jul 22, 2021·Dalton Transactions : an International Journal of Inorganic Chemistry·Ademola Soyemi, Tibor Szilvási
Oct 20, 2018·Journal of the American Chemical Society·David M H AscoughRobert S Paton
Aug 11, 2018·Journal of Chemical Theory and Computation·Yanfei GuanSteven E Wheeler

❮ Previous
Next ❯

Methods Mentioned

BETA
column chromatography
1
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.