High-Throughput Discovery and Evaluation of a General Catalytic Method for N-Arylation of Weakly Nucleophilic Sulfonamides
| Autor: | Graham E. Dobereiner, David C. Leitch, Janelle E. Steves, Damian P. Hruszkewycz, Joseph Becica, Jennifer M. Elward |
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| Rok vydání: | 2019 |
| Předmět: |
chemistry.chemical_classification
Steric effects 010405 organic chemistry Organic Chemistry chemistry.chemical_element 010402 general chemistry 01 natural sciences Biochemistry Combinatorial chemistry Coupling reaction 0104 chemical sciences Sulfonamide Catalysis chemistry Nucleophile Moiety Physical and Theoretical Chemistry Throughput (business) Catalytic method Palladium |
| Popis: | Sulfonamides are poor nucleophiles in Pd C-N coupling catalysis, hindering synthesis of densely-functionalized N,N-diaryl sulfonamide motifs relevant to medicinal chemistry. Through targeted high-throughput experimentation (HTE), we have identified the Pd/AdBippyPhos catalyst system as an effective and general method to construct this difficult to access moiety. In particular, AdBippyPhos is critical for the installation of heteroaromatic groups. Computational steric parameterization of the investigated ligands reveals the potential importance of remote steric demand, where a large cone angle combined with an accessible Pd center is correlated to successful catalysts for C-N coupling reactions. |
| Databáze: | OpenAIRE |
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