Direct C-H/C-X Coupling Methodologies Mediated by Pd/Cu or Cu: An Examination of the Synthetic Applications and Mechanistic Findings

Sara      De Ornellas; Thomas      E. Storr; Thomas      J. Williams; Christoph      G. Baumann; Ian      J.S. Fairlamb

Abstract

Organocopper chemistry has long been known to be powerful synthetic methodology leading to the generation of C-C, C-O, C-N, C-S and C-X bonds. Advances in catalytic and stoichiometric organometallic reactions for the formation of C-C bonds from unfunctionalised arenes, e.g. by activation-functionalisation of a C-H bond, provides diverse and applicable reaction conditions for direct functionalisation. This review covers the background, applications and recent advances made in the area of aromatic C-X/C-H-bond couplings promoted by copper and copper/palladium mixed systems. The efficacy and scope of these reactions are discussed and the different methodologies are placed into context. Mechanistic considerations and evidence are highlighted at appropriate junctures in the review.

Keywords: Copper, C-H Functionalisation, Palladium, Nucleosides, Imidazoles, Synthetic Applications, Mechanistic Findings, Organocopper chemistry, stoichiometric organometallic, arenes, heteroarenes, organometallic chemistry, co-catalytic system, Stille couplings, imidazole, methylthia-zoles, thiazole, formylthio-phene, iodobenzoate, Sonogashira reac-tion, copper(I) iodide, Ortho-Directed Functionalisations, bromostyrenes, Tetrafluoropyridine, fluoropyridine, Diaryliodonium Salts