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Ligand-free copper-catalysed N-arylation of methanesulfonamides with aryl bromides
Author
Tan, Yun Ru
Supervisor
Teo, Yong Chua
Tan, Swee Ngin
Abstract
The cross coupling of nucleophiles with electrophilic aromatic halides using transition metal salt is a robust synthetic method that is widely employed in the manufacture of medicinal agents, bioactives and polymeric materials. The traditional methods for generating C-N bonds have been accomplished using copper catalysts or the palladium-mediated Buchwald-Hartwig method. In most cases, the reactions must be conducted under stringent inert conditions and anhydrous solvents which limit industrial applications. In some instances, specially designed ligands have to be synthesized which further adds cost to the system. In this context, the catalytic systems should be economical and experimentally simple to be useful for large scale applications from an industrial viewpoint.
In this dissertation, we have shown an economical strategy for N-arylations of methane sulfonamides with a range of differently substituted aromatic bromides using copper catalysis under ligand-free condition. Reports on the use of aryl bromides under ligand free catalysis are very limited owing to lower reactivity compared to the iodo-counterparts. Moreover, the use of aryl bromides offers many advantages including lower toxicities and cost. This method was shown to afford product yields up to 80% under the best reaction conditions and have the following features: (i) highly efficient; (ii) high generality and applicable to a wide variety of substrates; (iii) uses cheap and sustainable copper catalyst at low loading to reduce overall cost and (iv) requires non-inert reaction conditions and simple to carry out.
In this dissertation, we have shown an economical strategy for N-arylations of methane sulfonamides with a range of differently substituted aromatic bromides using copper catalysis under ligand-free condition. Reports on the use of aryl bromides under ligand free catalysis are very limited owing to lower reactivity compared to the iodo-counterparts. Moreover, the use of aryl bromides offers many advantages including lower toxicities and cost. This method was shown to afford product yields up to 80% under the best reaction conditions and have the following features: (i) highly efficient; (ii) high generality and applicable to a wide variety of substrates; (iii) uses cheap and sustainable copper catalyst at low loading to reduce overall cost and (iv) requires non-inert reaction conditions and simple to carry out.
Date Issued
2022
Call Number
QD505 Tan
Date Submitted
2022