Benzoxazole or Benzothiazole as an Innate Directing Group for Palladium- and Ruthenium-Catalyzed Complementary C–H Arylation: Functionalization of Biorelevant Heterocyclic Scaffolds

Abstract

Benzoxazole and benzothiazole moiety have been used as innate directing handles for Pd(II)- and Ru(II)-catalyzed C–H arylation of bio-relevant heterocycles, 2-arylbenzoxazole and 2-arylbenzothiazole with diverse iodoarenes, following a complementarity of palladium-ruthenium catalysts. The induction of σ-donor ligands, such as N,N-dimethylacetamide to Pd(II) catalytic cycle and σ-donor/π-acceptor ligand, such as PPh3 to Ru(II) catalytic cycle enhances the arylation rate significantly and governed by the C–H acidity of C2-aryl ring of 2-arylbenzoxazole/2-arylbenzothiazole. The approaches have a broad substrate scope with respect to coupling partners to accommodate electron-neutral, electron-rich as well as electron-deficient iodoarenes plus C2-aryl unit of 2-arylbenzoxazoles/2-arylbenzothiazoles, exhibit a high degree of siteselectivity at ortho-C–H position, afford only mono-arylated derivatives in decent yields, functional groups tolerant, and applicable to ‘gram-scale’ production.