Computer-driven development of ylide functionalized phosphines for palladium-catalyzed Hiyama couplings

  • Palladium-catalyzed couplings of silicon enolates with aryl electrophiles are of great synthetic utility, but often limited to expensive bromide substrates. A comparative experimental study confirmed that none of the established ligand systems allows to couple inexpensive aryl chlorides with α-trimethylsilyl alkylnitriles. In contrast, ylide functionalized phosphines (YPhos) led to encouraging results. A statistical model was developed that correlates the reaction yields with ligand features. It was employed to predict catalyst structures with superior performance. With this cheminformatics approach, YPhos ligands were tailored specifically to the demands of Hiyama couplings. The newly synthesized ligands displayed record-setting activities, enabling the elusive coupling of aryl chlorides with α-trimethylsilyl alkyl nitriles. The preparative utility of the catalyst system was demonstrated by the synthesis of pharmaceutically meaningful α-aryl alkylnitriles, α-arylcarbonyls and biaryls.

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Metadaten
Author:Jonas F. GoebelORCiDGND, Julian LöfflerORCiDGND, Zhongyi ZengORCiDGND, Jens HandelmannGND, Albert HermannGND, Ilja RodsteinGND, Tobias GenschORCiDGND, Viktoria H. Däschlein-GessnerORCiDGND, Lukas J. GooßenORCiDGND
URN:urn:nbn:de:hbz:294-118842
DOI:https://doi.org/10.1002/anie.202216160
Parent Title (German):Angewandte Chemie International Edition
Publisher:Wiley-VCH
Place of publication:Weinheim
Document Type:Article
Language:English
Date of Publication (online):2025/03/14
Date of first Publication:2022/12/20
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Tag:Hiyama; machine learning; nitrils; palladium; phosphane ligands
Volume:62
Issue:9, Artikel e202216160
First Page:e202216160-1
Last Page:e202216160-9
Note:
Dieser Beitrag ist auf Grund des DEAL-Wiley-Vertrages frei zugänglich.
Institutes/Facilities:Lehrstuhl für Organische Chemie I
Dewey Decimal Classification:Naturwissenschaften und Mathematik / Chemie, Kristallographie, Mineralogie
open_access (DINI-Set):open_access
faculties:Fakultät für Chemie und Biochemie
Licence (English):License LogoCreative Commons - CC BY-NC 4.0 - Attribution-NonCommercial 4.0 International

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