Palladium-catalyzed cross-coupling reactions between organometallic nucleophilic reagents and electrophilic organic halides or pseudohalides emerged as powerful synthetic tools for the construction of C À C bonds.[1-2] Such catalytic coupling processes are applied to a wide array of fields, which range from biological sciences to materials chemistry. [3][4] Their applications to heteroaromatic substrates set the stage for convergent synthetic routes to valuable substituted heterocyclic structures.[5] Because of the necessity of limiting costly and contaminant metallic reagents, the research focus has shifted to the direct arylation of heteroaromatic substrates by the combined C À H/C À X activation (X = halide or pseudohalide).[6] This type of methodology presents the advantage of circumventing the preparation of organometallic nucleophilic reagents. It also avoids stoichiometric formation of metallic side products, from which undesired contamination could be appalling for pharmaceutical, agrochemical, and related biological applications.Reports of palladium-catalyzed direct arylations of heteroaromatics have described the use of organic bromides, [7] iodides, [8] triflates, [9] mesylates and tosylates, [10] sulfamates and phosphates, [11] iodonium salts, [12] and potassium trifluoroborates [13] as useful reagents. Organic chlorides remained noticeably uncommon partners, [14] despite the fact that among halides and pseudohalides, chlorides are arguably the most useful single class of substrates because of their straightforward access, their lower cost, and the wider diversity of available compounds. However, chloroarenes are most often unreactive under the conditions employed to couple other more reactive starting materials. Few monodentate electron-rich catalysts, [15] and a catalytic system based on a chelating diphosphane [16] have achieved a limited number of intermolecular couplings [17] between mostly unsubstituted or electron-deficient aryl chlorides and heteroaromatic compounds. Despite this remarkable progress, more sustainable catalytic systems, employing significantly less palladium/ligand catalyst, for the coupling of a wide array of diversely substituted aryl chlorides to heteroaromatic compounds have not yet been reported. Herein, we disclose a new air-stable, moisture and temperature tolerant palladium/ triphosphane system that is highly efficient for the direct arylation of substituted furan, pyrrole, thiophene, and thiazole substrates. Notably, these findings represent an economically attractive direct arylation of hetero-and diheteroaromatic substrates with chloroarenes by using less than 1 mol % of the palladium/ligand catalyst. This versatile system highlights also the potential of tridentate ferrocenyl polyphosphane ligands as air-stable, easy to handle auxiliaries in demanding intermolecular C À H/C À Cl activations.As a part of our program directed towards the development of robust polydentate auxiliaries for various crosscoupling reactions, [18] we probed various ferrocenyl polyphosphane ...

Preparation and characterization of the first examples of copper(I) ferrocenylpolyphosphine complexes are reported. The molecular structure of complex {P,P′,P′′-[1,1′,2,2′-tetrakis(diphenylphosphino)-4,4′di-tert-butylferrocene]iodocopper(I)} (1) was solved by X-ray diffraction studies, and its fluxional behavior in solution was investigated by VT-31 P NMR; both revealed a net triligated coordination preference of the ferrocenyl tetraphosphine Fc(P) 4t Bu with copper. The tetradentate ligand is an active auxiliary in Sonogashira alkynylation; therefore the general question of copper as a competitive coordination partner in the Pd/Cu-catalyzed Sonogashira reaction was raised and discussed. Electronically neutral, activated, and deactivated aryl bromides were employed for coupling with phenylacetylene with various [(Pd)/ (Cu)/(tetraphosphine)] systems. The catalytic investigations shown that 1 mol % of complex 1 in combination with palladium is far more effective and selective for Sonogashira coupling than 5 mol % of CuI and palladium in the coupling to phenylacetylene of the deactivated aryl bromide 4-bromoanisole. This system efficiently avoids the concurrent and deleterious consumption of phenylacetylene by formation of diyne or enynes. To our knowledge, this is the first time that this kind of high selectivity is induced in Sonogashira alkynylation by initial ligand complexation to copper instead of palladium. These results demonstrate that coordination of Cu halide cocatalyst is a factor that should no longer be neglected in mechanistic and applied studies of the Sonogashira reaction.