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.
The challenge of sustainability in modern chemistry will be met with new technologies and processes provided significant progress is made in several key research areas, such as the expansion of chemistry from renewable feedstock, the design of environmentally benign chemicals and solvents, the minimization of depletive resources, and the development of high‐performance catalysis. In this prospect, ligand chemistry is a pivotal science that links modern‐organic,‐inorganic, ‐organometallic, and ‐coordination chemistry through a vast number of valuable applications, precisely associated to catalysis. We review in this article our recent work on catalysis promoted by original ferrocenyl tetra‐, tri‐, and diphosphane ligands. New concepts, taking advantages of this family of branched multidentate ligands, have led to progress in homogeneous catalysis. The search for catalyst longevity and ultra‐low catalyst loadings (high turnover numbers), on the basis of multidentarity effects and robustness of the ferrocenyl backbone were focused on high‐value palladium‐catalyzed C–C cross‐couplings, such as Heck, Suzuki, and Sonogashira reactions. Low catalyst loading was also explored for C–N cross‐coupling in the allylic amination of achiral substrates. The advantages of this newly born family of ligands in the class of multidentate compounds are discussed in light of the valuable information gathered up to now on their reactivity, structure, and mechanistic behavior.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
The palladium‐catalyzed direct arylation of alkylated‐ furan, thiophene, and thiazole and benzoxazole heterocycles with electronically and sterically deactivated bromoarenes was selectively and efficiently promoted by ferrocenyl polyphosphanes. In this CH bond activation reaction of heteroaromatics, the performances of polydentate di‐, tri‐, and tetraphosphane ligands were compared, showing that the triphosphane 1,1′,2‐tris(diphenylphosphino)‐4‐tert‐butylferrocene 3 was the most effective for the coupling. The introduction of more electron‐donating (iPr) or electron‐withdrawing (furyl) groups on the phosphorus atoms did not improve the ligand performances. The coordination behavior of 3 towards palladium(II) and other group 10 metals, NiII and PtII, was studied and the corresponding 1,2‐P chelating phosphorus complexes were isolated in high yields and fully characterized by multinuclear 1H, 13C, 31P NMR (3⋅PdCl2, 3⋅PtCl2) and X‐ray structures (3⋅NiBr2). It was found that the triphosphane ligand 3 was able to accommodate bidentate chelating cis coordination to group 10 metals, and additionally a much rarely described bis monodentate trans configuration. The combination of these two modes of coordination in a multimetallic species was clearly evidenced for the first time for a ferrocenyl polyphosphane. This versatility in bonding is a clear difference of coordination potential of this catalytically more efficient triphosphane compared to analogous ferrocenyl di‐ or tetraphosphanes.
The synthesis of novel substituted cyclopentadienyl salts that incorporate both a congested branched alkyl group (tert-butyl, (triphenyl)methyl, or tri(4-tert-butyl)phenylmethyl) and a phosphanyl group is reported. The introduction of either electron-withdrawing or electron-donating substituents (furyl, i-propyl, cyclohexyl, tert-butyl) on P atoms was generally achieved in high yield. The modular synthesis of ferrocenyl polyphosphanes from an assembly of these cyclopentadienyl salts was investigated, leading to the formation of new triphosphanes (denoted as 9-12) and diphosphanes (denoted as 14-16). The resulting phosphanes are not sensitive to air or moisture, even when electron-rich substituents are present. This set of polyphosphanes displays varied conformational features, which are discussed in the light of their multinuclear NMR characterization in solution and of the X-ray solid state structure of the representative triphosphane 1,2-bis(diphenylphosphanyl)-1'-(diisopropylphosphanyl)-3'-(triphenyl)methyl-4-tert-butyl ferrocene, 11. In particular, the existence of a range of significantly different nonbonded ("through-space", TS) spin-spin coupling constants between heteroannular P atoms, for the triphosphanes of this class, allowed their preferred conformation in solution to be appraised. The study evidences an unanticipated flexibility of the ferrocene platform, despite the presence of very congested tert-butyl and trityl groups. Herein, we show that, contrary to our first belief, the preferred conformation for the backbone of ferrocenyl polyphosphanes can not only depend on the hindrance of the groups decorating the cyclopentadienyl rings but is also a function of the substituents of the phosphanyl groups. The interest of these robust phosphanes as ligands was illustrated in palladium catalysis for the arylation of n-butyl furan with chloroarenes, using direct C-H activation of the heteroaromatic in the presence of low metal/ligand loadings (0.5-1.0 mol %). Thus, 4-chlorobenzonitrile, 4-chloronitrobenzene, 4-chloropropiophenone, and 4-(trifluoromethyl)chlorobenzene were efficiently coupled to n-butyl furan, using Pd(OAc)(2) associated to the new diphosphane ligands 1,1'-bis(diisopropylphosphanyl)-3,3'-di(triphenyl)methyl ferrocene (15) or 1,1'-bis(dicyclohexylphosphanyl)-3,3'-di(triphenyl)methylferrocene (16), which respectively hold the electron-rich -Pi-Pr(2) and -PCy(2) groups.
The present study deals with the conformational control of the metallocene backbone within ferrocenyl polyphosphane ligands and their performance in the highly topical palladium-catalyzed heteroaromatics arylation by direct C-H activation. New substituted cyclopentadienyl rings were synthesized, which allowed the assembling of original tri-and diphosphanes. The bulky cyclopentadienyl lithium salts diphenylphosphino-3-(triphenyl)methylcyclopentadienyllithium (4) and 1,2-bis(diphenylphosphino)-4-(triphenyl)methylcyclopentadienyllithium (5) were prepared in excellent yield. The assembling of these new hindered cyclopentadienyl salts (Cp) with other Cp fragments was performed in order to prepare ferrocenyl ligands with controlled conformation. A comparison of conformations of 1,1′,2-tris(diphenylphosphino)-3′,4-di-tert-butylferrocene (3) and 1,1′,2-tris(diphenylphosphino)-3′-(triphenyl)methyl-4tert-butylferrocene (6) allowed us to determine, for the first time, the conditions of an efficient control of the orientation of the phosphino substituents on the ferrocene backbone in the absence of an ansabridge. The characterization of these metallo-ligands, by multinuclear NMR in solution and by X-ray diffraction in the solid state, focused on nonbonded J PP spin-spin couplings. These unusual couplings are especially useful for assessing the conformation of the ferrocene backbone in solution. The palladium complexes of the triphosphane ligand 6 and the diphosphane 1,1′-bis(diphenylphosphino)-3,3′-di(triphenyl)methylferrocene ( 7) were successfully used in the direct C-H activation of electron-rich heteroaromatics for coupling to demanding aryl bromides, whether electron rich and/or sterically congested. Products such as 2-butyl-5-(4-methoxyphenyl)furan (10), 2-butyl-5-o-tolylfuran (11), and thiophene analogues (12 and 13) were obtained in yields higher than 90%. The NMR examination of the reaction of [PdCl(η 3 -C 3 H 5 )] 2 with ligands 6 and 7 allowed us to determine the coordination chemistry of the precatalysts. The allylic palladium complexes 8 and 9 confirmed the unusual conformation present in 6. As a consequence, the selective and "genuinely" tridentate bonding of a triphosphane to one palladium center is reported. This seldom observed coordination mode is a direct consequence of the successful ferrocene backbone conformation control.
The modular design of polyphosphines, diversely functionalized for facile immobilization on virtually any kind of support, is reported. Previously unobserved ABCD (31)P NMR spin-spin systems evidence the control exercised on the polyphosphines conformation. We illustrate the catalytic performance at low Pd loading of the recyclable immobilized polyphosphines in C-C bond formation reactions.
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