Tunable and Cooperative Catalysis for Enantioselective Pictet-Spengler Reaction with Varied Nitrogen-Containing Heterocyclic Carboxaldehydes.


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:
08 11 2021
Historique:
revised: 24 08 2021
received: 20 07 2021
pubmed: 7 9 2021
medline: 15 12 2021
entrez: 6 9 2021
Statut: ppublish

Résumé

Herein we report an organocatalytic enantioselective functionalization of heterocyclic carboxaldehydes via the Pictet-Spengler reaction. Through careful pairing of novel squaramide and Brønsted acid catalysts, our method tolerates a breadth of heterocycles, enabling preparation of a series of heterocycle conjugated β-(tetrahydro)carbolines in good yield and enantioselectivity. Careful selection of carboxylic acid co-catalyst is essential for toleration of a variety of regioisomeric heterocycles. Utility is demonstrated via the three-step stereoselective preparation of pyridine-containing analogues of potent selective estrogen receptor downregulator and U.S. FDA approved drug Tadalafil.

Identifiants

pubmed: 34487418
doi: 10.1002/anie.202109694
pmc: PMC8556314
mid: NIHMS1738955
doi:

Substances chimiques

Aldehydes 0
Benzaldehydes 0
Carbolines 0
Carboxylic Acids 0
Heterocyclic Compounds 0
3-pyridinaldehyde 840R4IDQ1T
Nitrogen N762921K75
benzaldehyde TA269SD04T

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

24573-24581

Subventions

Organisme : NIGMS NIH HHS
ID : R35 GM132092
Pays : United States
Organisme : NIH HHS
ID : R35 GM132092
Pays : United States
Organisme : eli lilly and company

Informations de copyright

© 2021 Wiley-VCH GmbH.

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Auteurs

Yuk-Cheung Chan (YC)

Department of Chemistry, Yale University, New Haven, CT, 06520, USA.

Marcus H Sak (MH)

Department of Chemistry, Yale University, New Haven, CT, 06520, USA.

Scott A Frank (SA)

Synthetic Molecule Design and Development, Eli Lilly and Company, Indianapolis, IN, 46285, USA.

Scott J Miller (SJ)

Department of Chemistry, Yale University, New Haven, CT, 06520, USA.

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Classifications MeSH