1. Coordination catalysts for Chan-Evans-Lam couplings
Chan-Evans-Lam (CEL) couplings are oxidative couplings of nucleophiles with an arylboronic acid. Compared to the Ullmann-Goldberg reaction or Buchwald-Hartwig aminations catalyzed by palladium or copper, CEL couplings proceed under much milder conditions, often at room temperature, and are thus more attractive for complicated and sensitive substrates. While CEL couplings have now been successfully employed for a large variety of N-, O-, S-, and even C-nucleophiles, from the very beginning researchers remarked the “somewhat capricious nature of this reaction”, and its exceedingly high substrate-dependency. Early – and even current – work on CEL couplings thus report optimized reaction conditions which differ strongly even for closely related substrates such as amines and anilines. Typical catalysts in CEL couplings are simple copper salts, in most cases copper acetate. We hypothesized that the large variety of reaction conditions in CEL couplings and the strong dependence of reactivity on them is related to the use of simple copper salts as catalysts. Solvent and added base are required to solubilize and activate the copper salt, and base and counteranion play a role in the formation of dinuclear copper-boron complexes as a first step in the transmetallation. Incorporating these features into the ligand of a coordination complex could provide catalysts with a more general reaction protocol and – hopefully – increased reactivities. We have recently reported the use of pyridylimino arylsulfonate complexes for which we reported a high reactivity towards amines, anilines, and N-heterocycles, and which showed some of the highest activities in CEL couplings, in particular for challenging substrates. Despite these advances, general catalysts for CEL couplings remain elusive. The following project aims to investigate electronic and steric factors governing reactivity in CEL couplings with coordination complexes and use these understandings in the design of improved catalysts.
Research area, student roles & skills
Research area: We are a synthetic inorganic chemistry group, with a strong focus on catalytic applications and green chemistry. A typical project involves preparation of ligands (sometimes known, sometimes new), coordination complexes (which might involve air-sensitive chemistry) and their application in catalysis. Evaluation of catalytic results is followed by complex optimization. Typically summer students participate in the project of a graduate student with an independent sub-project. Depending on the amount of results obtained, they might be co-authors of the resulting publications. Although not typical, some summer students were first authors of smaller publications.
Student roles:
Independent (under supervision of a graduate student) preparation of ligands and complexes and their application in catalysis. Guided interpretation of results.
Skills required:
Essential skills for this project require basic organic and inorganic synthesis and ease with the interpretation of simple NMR spectra. Other skills will be taught during the internship, if required, and might include: air-sensitive techniques (glove box, Schlenk), independent recording of NMR spectra, kinetic analyses, GC-MS analyses.