Dual Ligand Enabled Nondirected C-H Chalcogenation of Arenes and Heteroarenes

ABSTRACT: Chalcogenide motifs are present as principal moieties in a vast array of natural products and complex molecules. Till date, the construction of these chalcogen motifs has been restricted to either the use of directing groups or the employment of a large excess of electronically activated arenes, typically employed as a cosolvent. Despite being highly effective, these methods have their own limitations in the step economy and the deployment of an excess amount of arenes. Herein, we report the evolution of a catalytic system employing arene-limited, nondirected thioarylation of arenes and heteroarenes using a complimentary dual-ligand approach. The reaction is controlled by a combination of steric and electronic factors, and the utilization of a suitable ligand enables the generation of products on a complimentary spectrum to that generated by classical methods. The combination of ligands remains imperative in the reaction protocol with theoretical calculations pointing towards a monoprotected amino acid ligand being crucial in the concerted metalation deprotonation (CMD) mechanism by a characteristic [5,6]-palladacyclic transition state, while the pyridine moiety assists in the active catalyst species formation and product release. Combined experimental and computational mechanistic investigations point toward the C???H activation step being both regio- and rate-determining. Interestingly, oxidative addition of the diphenyl disulfide substrate is found to be unlikely, and an alternative transmetalation-like mechanism involving the Pd???Ag heterometallic complex is proposed to be operative.

Automated summary

The article reports the development of a catalytic system for the synthesis of chalcogen motifs using a complimentary dual-ligand approach. The reaction is controlled by steric and electronic factors, and the use of suitable ligands allows the generation of products different from classical methods. The combination of ligands is crucial in the reaction protocol, and the mechanism of the reaction has been investigated through theoretical calculations and experiments.