Enantio- and Regioselective Copper-Catalyzed 1,2-Dearomatization of Pyridines.

Alkyne Asymmetric Catalysis Copper Dearomatization Pyridine Stackphos

Journal

Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543

Informations de publication

Date de publication:
27 Nov 2023
Historique:
received: 01 09 2023
medline: 11 10 2023
pubmed: 11 10 2023
entrez: 11 10 2023
Statut: ppublish

Résumé

A copper-catalyzed dearomative alkynylation of pyridines is reported with excellent regio- and enantioselectivities. The synthetically valuable enantioenriched 2-alkynyl-1,2-dihydropyridine products afforded are generated from the readily available feedstock, pyridine, and commercially available terminal alkynes. The three-component reaction between a pyridine, a terminal alkyne, and methyl chloroformate employs copper chloride and StackPhos, a chiral biaryl P,N- ligand, as the catalytic system. Under mild reaction conditions, the desired 1,2-addition products are delivered in up to 99 % yield with regioselectivity ratios up to 25 : 1 and enantioselectivities values of up to 99 % ee. Activated and non-activated terminal alkynes containing a wide range of functional groups are well tolerated. Even acetylene gas delivered mono-alkynylated products in high yield and ee. Application of the methodology in an efficient enantioselective synthesis of the chiral piperidine indolizidine, coniceine, is reported.

Identifiants

pubmed: 37820350
doi: 10.1002/anie.202312967
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e202312967

Subventions

Organisme : NIH HHS
ID : S10 OD021758-01A1
Pays : United States
Organisme : NIH HHS
ID : S10 OD021758-01A1
Pays : United States

Informations de copyright

© 2023 Wiley-VCH GmbH.

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Auteurs

Mukesh Pappoppula (M)

Department of Chemistry and Florida Center for Heterocyclic Compounds, University of Florida, P.O. Box 117200, Gainesville, FL 32611, United States.

Kathryn L Olsen (KL)

Department of Chemistry and Florida Center for Heterocyclic Compounds, University of Florida, P.O. Box 117200, Gainesville, FL 32611, United States.

Devin R Ketelboeter (DR)

Department of Chemistry and Florida Center for Heterocyclic Compounds, University of Florida, P.O. Box 117200, Gainesville, FL 32611, United States.

Aaron Aponick (A)

Department of Chemistry and Florida Center for Heterocyclic Compounds, University of Florida, P.O. Box 117200, Gainesville, FL 32611, United States.

Classifications MeSH