Functionalisation of aromatic C-H bonds with dicarbene transition metal catalysts

Content Provider	Semantic Scholar
Author	Buscemi, Gabriella
Copyright Year	2009
Abstract	The present research project concerns the catalytic application of transition metal dicarbene complexes in aromatic C-H bond functionalisation/activation reactions. The efficiency of this kind of complexes has been mainly examined in the hydroarylation of alkynes (Fujiwara reaction), which involves the addition of arenes to a wide range of internal and terminal alkynes. It was already known that this reaction is catalysed by simple palladium(II) compounds, such as Pd(OAc)2, in a trifluoroacetic acid environment. It occurs at room temperature and is characterised by a high and quite unusual regio- and stereoselectivity: remarkably the thermodynamically less favoured cis-arylalkenes are often obtained as major products. The Fujiwara reaction appears very promising from the synthetic point of view also because both the inter- and intra-molecular versions of the reaction are known, thus expanding its applicability to the functionalisation of aromatic heterocycles and to the synthesis of coumarins. However, the possible industrial application requires the optimisation of the reaction conditions since the reaction is often quite slow, needs an excess of arene substrate, and it usually requires 1-5 mol% palladium which heavily affects the cost of the process. In the literature other metal centres, such as platinum(II), gold(I) and gold(III) have been successfully employed as alternative catalysts, but their efficiency appears to be lower than that of palladium(II). Also the use of non-noble, electrophilic metal centres has been reported, but their reactivity is lower and/or their applicability limited to aryl-acetylenes. The initial aim of the present research project was to improve the yields of the reaction and decrease the catalyst loading. N-heterocyclic carbene ligands can improve the stability of the catalyst under the reaction conditions as well as its reactivity. Monocarbene Pd(II) complexes (IPr)Pd(OAc)2 and (IPr)Pd(OOCCF3)2 (IPr = N,N’-bis(2,6-diisopropylphenyl)-imidazol-2-ylidene) are indeed the only complexes which have been reported to be active in the Fujiwara reaction in the absence of other promoters, though their activity is comparable to that of simple Pd(OAc)2. In the initial part of this research work it has been shown that dicarbene palladium(II) complexes are able to catalyse the hydroarylation of alkynes at 80 °C, with excellent conversions and selectivities at low catalyst loading (0.1 mol%) and with equimolar amounts of reagents. These dicarbene complexes have displayed a reactivity higher than simple palladium acetate and monocarbene palladium complex (12) tested in the same reaction conditions. Dicarbene platinum(II) complexes have also been employed and have performed an efficiency superior than Pt salts based systems reported in the literature. The optimised protocol has resulted quite general with respect to the alkyne, while its applicability to arene substrates is at present limited to electron-rich molecules. However this is a limitation occurring with all Pd- and Pt-catalytic systems reported in the literature for the hydroarylation reaction. Another part of the work has concerned the identification of the catalytic active species. Mechanistic studies, performed at 80 °C and made varying both the dicarbene ligand and the halide ligands at the metal, have revealed that the catalytic active species retains the dicarbene ligand in its coordination sphere. Halide anionic ligands are instead removed from the complex by exchange with the trifluoroacetate anion deriving from the acidic solvent media. The catalytic efficiency of the complex does not depend on the kind of halide ligands, but it is influenced by the nature of the dicarbene ligand. Parallel electrochemical studies have been therefore made to evaluate the electronic density at the metal centre in different dicarbene complexes. The aim is to clarify if the catalytic efficiency of the complex is predominantly influenced by its electronic or steric properties, in order to design the best catalyst for the reaction. Cyclic voltammetries have shown that the electronic density at the metal changes depending on the dicarbene ligand, but the scale of reduction potentials Pd(II)-Pd(0) is not correlated to the scale of catalytic activity. This suggests that the catalytic efficiency of such complexes in the Fujiwara reaction is predominantly influenced by the steric hindrance at the metal centre. A successive optimisation of the reaction parameters (nature of the solvent system, concentration of the reagents, reaction temperature and use of co-catalysts) has allowed to further increase the selectivity of the reaction under mild reaction conditions. It has indeed found that, in the presence of silver salts (like AgTFA) as co-catalysts, the reaction can be run at room temperature, with conversion higher than the one displayed by palladium acetate in the same reaction conditions. Differently from at 80 °C, isomerisation to the more thermodinamically stable trans-arylalkene and hydrolysis reactions of the ester functions do not occur at room temperature, so that selectivity towards the cis-arylalkene product has been significantly improved. Finally, the optimised catalytic system has been used with other substrates, such as aromatic heterocycles, obtaining also in this case high yields in products. However, the selectivity towards the desired product decreases by the formation of adducts heterocycle/alkyne 2/1. A preliminary investigation of the reaction mechanism through kinetic studies has been also started. There is indeed at present some controversy about the reaction mechanism, that could be an electrophilic arene metalation or a Friedel-Crafts-type alkenylation. The kinetic law has resulted of the first order in palladium and, in the adopted reaction conditions, of the first order also in arene or in alkyne. It remains to evaluate the dependence of the kinetic law from the concentration of the acid, which seems to have an important role in the reaction mechanism. However, it needs to be used in large excess with respect to the substrates and probably its principal role is to hydrolyse the vinyl-palladium species, invoked as catalytic intermediate in both the proposed mechanisms. Dicarbene complexes of palladium(II) and platinum(II) have been also tested in other aromatic C-H bond functionalisation reactions, such as the ortho-functionalisation of acetanilides.
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://paduaresearch.cab.unipd.it/1693/1/TesiGabriellaBuscemipdf.pdf
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article