A palladium-catalyzed asymmetric Markovnikov hydroaminocarbonylation of alkenes with anilines has been developed for the atom-economical synthesis of 2-substituted propanamides bearing an α-stereocenter. A novel phosphoramidite ligand was discovered which exhibited very high reactivity and selectivity in the reaction. This asymmetric Markovnikov hydroaminocarbonylation employs readily available starting materials and tolerates a wide range of functional groups, thus providing a facile and straightforward method for the regio- and enantioselective synthesis of 2-substituted propanamides under ambient conditions. Mechanistic studies revealed that the reaction proceeds through a palladium hydride pathway.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jacs.0c11249 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A Type of Chiral C-Symmetric Arylthiol Catalyst for Highly Enantioselective Anti-Markovnikov Hydroamination.
J Am Chem Soc
June 2024
Shanghai Key Laboratory of Green Chemistry and Chemical Processes, State Key Laboratory of Petroleum Molecular & Process Engineering, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
The development of chiral hydrogen donor catalysts is fundamental in the expansion and innovation of asymmetric organocatalyzed reactions via an enantioselective hydrogen atom transfer (HAT) process. Herein, an unprecedented type of chiral C-symmetric arylthiol catalysts derived from readily available enantiomeric lactate ester was developed. With these catalysts, an asymmetric anti-Markovnikov alkene hydroamination-cyclization reaction was established, affording a variety of pharmaceutically interesting 3-substituted piperidines with moderate to high enantioselectivity.
View Article and Find Full Text PDFEnantioselective synthesis of chiral α,α-dialkyl indoles and related azoles by cobalt-catalyzed hydroalkylation and regioselectivity switch.
Nat Commun
May 2024
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, 650500, Kunming, China.
General, catalytic and enantioselective construction of chiral α,α-dialkyl indoles represents an important yet challenging objective to be developed. Herein we describe a cobalt catalyzed enantioselective anti-Markovnikov alkene hydroalkylation via the remote stereocontrol for the synthesis of α,α-dialkyl indoles and other N-heterocycles. This asymmetric C(sp)-C(sp) coupling features high flexibility in introducing a diverse set of alkyl groups at the α-position of chiral N-heterocycles.
View Article and Find Full Text PDFCatalyst-Controlled Regiodivergent and Enantioselective Formal Hydroamination of N,N-Disubstituted Acrylamides to α-Tertiary-α-Aminolactam and β-Aminoamide Derivatives.
Angew Chem Int Ed Engl
May 2023
Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, P. R. China.
Enantioenriched α-tertiary-α-aminoacid and α-chiral-β-aminoacid derivatives play an important role in biological science and pharmaceutical chemistry. Thus, the development of methods for their synthesis is highly valuable and yet remains challenging. Herein, an unprecedented catalyst-controlled regiodivergent and enantioselective formal hydroamination of N,N-disubstituted acrylamides with aminating agents has been developed, accessing enantioenriched α-tertiary-α-aminolactam and α-chiral-β-aminoamide derivatives.
View Article and Find Full Text PDFNickel-catalyzed regio- and enantio-selective Markovnikov hydromonofluoroalkylation of 1,3-dienes.
Chem Sci
November 2022
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, Shanghai Key Laboratory of Green Chemistry and Chemical Processes, East China Normal University Shanghai 200062 China
A highly enantio- and regio-selective Markovnikov hydromonofluoro(methyl)alkylation of 1,3-dienes was developed using redox-neutral nickel catalysis. It provided a facile strategy to construct diverse monofluoromethyl- or monofluoroalkyl-containing chiral allylic molecules. Notably, this represents the first catalytic asymmetric Markovnikov hydrofluoroalkylation of olefins.
View Article and Find Full Text PDFProbing the Free Energy Landscape of Organophotoredox-Catalyzed Anti-Markovnikov Hydrofunctionalization of Alkenes.
J Am Chem Soc
September 2022
Department of Chemistry, Binghamton University, Binghamton, New York 13902, United States.
Experimental C kinetic isotope effects (KIEs) provide unprecedented mechanistic insight into three intermolecular anti-Markovnikov alkene hydrofunctionalization reactions─hydroesterification, hydroamination, and hydroetherification─enabled by organophotoredox catalysis. All three reactions are found to proceed via initial oxidation of the model alkenes to form a radical cation intermediate, followed by sequential nucleophilic attack and hydrogen-atom transfer to deliver the hydrofunctionalized product. A normal C KIE on the olefinic carbon that undergoes nucleophilic attack provides qualitative evidence for rate-limiting nucleophilic attack in all three reactions.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!