Theoretical prediction of selectivity in kinetic resolution of secondary alcohols catalyzed by chiral DMAP derivatives

Journal of the American Chemical Society
Evgeny LarionovHendrik Zipse

Abstract

The mechanism of esterification of the secondary alcohol 1-(1-naphthyl)ethanol 9 by isobutyric anhydride catalyzed by 4-pyrrolidinopyridine (PPY, 11) and a series of single enantiomer atropisomeric 4-dialkylaminopyridines 8a-g has been studied computationally at the B3LYP/6-311+G(d,p)//B3LYP/6-31G(d) level. Comparison of the levels of enantioselectivity predicted computationally with the results obtained experimentally allowed the method to be validated. The value of the approach is demonstrated by the successful prediction that a structural modification of an aryl group within the catalyst from phenyl to 3,5-dimethylphenyl would lead to improved levels of selectivity in this type of kinetic resolution (KR) reaction, as was subsequently verified following synthesis and evaluation of this catalyst (8d). Experimentally, the selectivity of this type of KR is found to exhibit a significant deuterium isotope effect (for 9 vs d(1)-9).

References

Jun 9, 2005·Angewandte Chemie·Edwin Vedejs, Mara Jure
Oct 4, 2005·Journal of Computational Chemistry·William L Jorgensen, Julian Tirado-Rives
Mar 28, 2006·Organic Letters·Vladimir B Birman, Ximin Li
Aug 26, 2006·The Journal of Organic Chemistry·Shinji YamadaYukiko Akiyama
Oct 6, 2006·Organic Letters·Vladimir B Birman, Lei Guo
Nov 2, 2006·Journal of the American Chemical Society·Forrest O Arp, Gregory C Fu
Dec 13, 2007·Chemical Reviews·Ryan P Wurz
Jul 12, 2008·Angewandte Chemie·Christian E MüllerPeter R Schreiner
Sep 27, 2008·Journal of the American Chemical Society·Ximin LiVladimir B Birman
Jun 19, 2010·The Journal of Organic Chemistry·Trisha A DuffeyEdwin Vedejs
Feb 10, 2011·Organic Letters·Matthew R CrittallDavid R Carbery
Jun 22, 2011·Angewandte Chemie·Christian E Müller, Peter R Schreiner

❮ Previous
Next ❯

Citations

Mar 24, 2016·Journal of the American Chemical Society·David W PiotrowskiMark T Barrila
Mar 22, 2018·Organic & Biomolecular Chemistry·Gaoyuan MaMukund P Sibi
May 30, 2020·Chemical Communications : Chem Comm·Bo JiangYing-Chun Chen
Oct 25, 2016·Chemistry : a European Journal·Stefania F MusolinoAndrew D Smith
Aug 12, 2015·Angewandte Chemie·J Philipp Wagner, Peter R Schreiner
Oct 23, 2020·Angewandte Chemie·Benjamin PöllothHendrik Zipse
Dec 15, 2018·Chemistry : a European Journal·Shen QuAndrew D Smith
Feb 9, 2021·The Journal of Organic Chemistry·Stefanie MayrHendrik Zipse
Feb 23, 2021·The Journal of Organic Chemistry·Alexander SeitzPeter R Schreiner
Oct 17, 2013·Organic Letters·Alexander J Wagner, Scott D Rychnovsky
Nov 18, 2020·Organic Letters·Daniel MulryanMark R Crimmin
Oct 30, 2020·Journal of the American Chemical Society·Ming-Sheng XieHai-Ming Guo
Dec 7, 2018·Chemical Reviews·Shinji Yamada
Aug 1, 2014·The Journal of Organic Chemistry·Pascal PatschinskiHendrik Zipse

❮ 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.