Franc Požgan

Ligand-less palladium-catalyzed direct 5-arylation of thiophenes at low catalyst loadings

Ligand-less Pd(OAc)2 provides a very efficient catalyst for the direct 5-arylation of thiophene derivatives. With this catalyst, a low palladium concentration (0.1–0.001 mol%) should be employed in order to obtain high yields of coupling products. At higher concentrations a fast formation of inactive “Pd black” generally occurs. Substrates/catalysts ratios up to 100000 can be employed with the most reactive aryl bromides. A very wide variety of functional groups is tolerated on both coupling partners. The major waste of this reaction is HBr associated with KOAc. Therefore this procedure is more economically and environmentally attractive than the traditional cross-coupling procedures employing organometallic derivatives.

Ligand‐Free Palladium‐Catalysed Direct Arylation of Heteroaromatics Using Low Catalyst Loadings

The arylation of heteroaromatics is an important field for research in organic synthesis. Palladium-catalysed Suzuki, Negishi or Stille cross-couplings are among the most important methods to perform such reactions. However, they require the preparation of an organometallic derivative and lead to the production of an organometallic salt (MX) as by-product. In 1990, Ohta et al. reported the direct arylation of thiophenes, furans or thiazoles with aryl halides through C H bond activation in moderate to good yields using 5 mol% [Pd ACHTUNGTRENNUNG(PPh3)4] as catalyst. Since these exciting results, the palladium-catalysed direct arylation of heterocyclic derivatives with aryl halides or triflates has proved to be a powerful method for the synthesis of heterobiaryls. 4] This method provides a cost-effective and environmentally attractive procedure for the preparation of arylated heteroaromatics. The major drawback of the reported procedures is that they generally require loadings of 5– 10 mol% catalyst. Recently, Heck and Suzuki reactions under low catalyst loading (0.1–0.01 mol%) using ligand-free catalyst Pd ACHTUNGTRENNUNG(OAc)2 have been described by de Vries and co-workers. 6] They demonstrated that soluble palladium(0) colloids or nanoparticles are formed at elevated temperature when Pd ACHTUNGTRENNUNG(OAc)2 is employed as catalyst precursor and that the Heck or Suzuki reaction takes place through the interaction of the arylating agent with the palladium atoms in the outer rim of the nanoparticles. This leads to formation of monomeric or dimeric anionic palladium complexes that undergo the usual steps of the Heck or Suzuki reaction mechanisms. So far, to our knowledge, all the procedures reported for the arylation through C H bond activation of heteroaromatics using ligand-free catalysts such as Pd ACHTUNGTRENNUNG(OAc)2 have required 5– 10 mol% catalyst, except for one procedure in which only 1 mol% was employed. In fact, such couplings under low concentrations of catalyst employ palladium associated to sophisticated ligands. Therefore, the development of more effective conditions for the direct coupling of heteroaromatics with aryl halides under low catalyst loadings (<0.1 mol%), would be a considerable advantage for industrial applications and for sustainable development. Here, we report on ligandless palladium-catalysed direct arylation of heteroaromatics using low catalyst loadings. First, by employing the low catalyst loading procedure described by de Vries and co-workers (elevated reaction temperature, polar solvent, acetate as base and no ligand on palladium), we observed that the coupling of 4-bromoacetophenone with 2-npropylthiazole using as little as 0.01 mol% Pd ACHTUNGTRENNUNG(OAc)2 as catalyst led selectively to the 5-arylated thiazole 1 with complete conversion of the aryl bromide and a very high yield of isolated compound (Scheme 1; Table 1, entry 1).

Low catalyst loading ligand-free palladium-catalyzed direct arylation of furans: an economically and environmentally attractive access to 5-arylfurans

The direct 5-arylation of furans at very low catalyst loading using Pd(OAc)2 as catalyst without added ligand proceed in high yields. Turnover numbers up to 10000 have been obtained for the coupling of several activated aryl bromides. A wide range of functions on the furan or aryl bromide is tolerated.

Advances in Catalyst Systems for the Asymmetric Hydrogenation and Transfer Hydrogenation of Ketones

Hydrogenation of prochiral ketones using chiral transition-metal catalysts represents the cleanest way to access enantiomerically enriched secondary alcohols, which are important building blocks in fine chemicals synthesis. Despite excellent activity, selectivity and compatibility of metal complexes with variety of functional groups, no universal catalysts exist. In this article we summarize the advances in catalyst systems for the asymmetric homogenous and heterogenous hydrogenation of ketones that have been made in past decade. The development of catalysts is oriented in reaching as high as activity with low catalyst loadings, using “greener’’ conditions, and ensuring good recyclability of catalysts. Even though ruthenium complexes represent the largest part of the catalysts, other metals rapidly penetrate this field.

Migration of an acyl group in the pyrazole system: synthesis of 1-acyl-3-hydroxy-1H-pyrazoles and related derivatives. A new preparation of N,N′-diacylhydrazines

A new general method for the synthesis of 1-acyl-3-hydroxy-1H-pyrazoles 5a–f and related derivatives 5g–i starting from 4-ethoxymethylene-2-phenyloxazol-5(4H)-one (1) and hydrazides, 4-phenylsemicarbazide, 4-phenylthiosemicarbazide and benzyl carbazate in boiling dioxane is described. The method includes a migration of an acyl or related unit. The X-ray study and NMR spectroscopic examination confirmed the structure of the products. A one-pot synthesis of N,N′-diacylhydrazines from hydrazides by the assistance of oxazolone 1 is also presented.

Novel triazole-based ligands and their zinc(II) and nickel(II) complexes with a nitrogen donor environment as potential structural models for mononuclear active sites

Three new 1,2,3-triazole-based ligands with an N,N,N coordination core were prepared using a convergent synthetic protocol starting from racemic 2-amino-1-phenylethanol. They were tested as chelators for biorelevant ZnII or NiII ions. An N,N,N ligand with a terminal amino functionality coordinated the ZnII in a bidentate fashion, not including the triazole nitrogen. The ligand with two pendant 2-pyridyl groups acted as a tridentate ligand without an N2-triazole coordination to ZnII, while the ligand containing one 2-pyridyl group acted as an inverse-click chelator for NiII ions.

Metal-Catalysed Transfer Hydrogenation of Ketones

We highlight recent developments of catalytic transfer hydrogenation of ketones promoted by transition metals, while placing it within its historical context. Since optically active secondary alcohols are important building blocks in fine chemicals synthesis, the focus of this review is devoted to chiral catalyst types which are capable of inducing high stereoselectivities. Ruthenium complexes still represent the largest part of the catalysts, but other metals (e.g. Fe) are rapidly penetrating this field. While homogeneous transfer hydrogenation catalysts in some cases approach enzymatic performance, the interest in heterogeneous catalysts is constantly growing because of their reusability. Despite excellent activity, selectivity and compatibility of metal complexes with a variety of functional groups, no universal catalysts exist. Development of future catalyst systems is directed towards reaching as high as possible activity with low catalyst loadings, using “greener” conditions, and being able to operate under mild conditions and in a highly selective manner for a broad range of substrates.

Recent Applications Of Alkene Metathesis For Fine Chemical And Supramolecular System Synthesis

Alkene metathesis has become a synthetic method that has strongly modified approaches in the building of complex molecules. The review will concentrate on the recent applications of ring-closing metathesis (RCM) and cross- metathesis (CM) reactions for the design of useful molecules and architectures: new functional macrocycles (RCM) and multifunctional linear alkenes (CM), but also cyclic ligands, rotaxanes, catenanes, and supramolecular systems.

A simple and efficient synthesis of 2-imidazolin-2-ones

We report on the reactions of diazenes 1 and 2 with 1,3-dicarbonyl compounds. The first step involves a regioselective attack of the diazene on the active methylene group, giving the Michael adducts 3 or 4, and can be performed either in the presence of sodium acetate or DBN (1,5-diazabicyclo[4.3.0]non-5-ene). The Michael adducts underwent ring-closure leading to 2-imidazolidinones 5 or 6 which were isolated in some cases. We found that 5 or 6 easily eliminated water in the presence of an acid to give imidazolin-2-ones 7 or 8 as the final products. The rate-determining step of this last mentioned process depends on the stereochemistry at C4 and C5 of the initial 2-imidazolidinone. A one-pot procedure to produce 7 or 8 directly from the diazene and the appropriate dicarbonyl partner is also described.

Synthesis and Reactivity of 2‐Arylquinazoline‐halido‐ruthenacycles in Arylation Reactions

The synthesis of a range of new cyclometallated organoruthenium(II) complexes through the ortho‐C−H activation of the aryl group in 2‐aryl‐substituted quinazolines with [RuX2(p‐cymene)]2 is described. The beneficial effect of the carboxylate ligand on both the cyclometallation and the further arylation reaction step was demonstrated. Mechanistic studies reveal that bromide and iodide anions decelerate the arylation process by an in situ ligand exchange reaction. Additionally, a detailed NMR spectroscopy investigation was performed to explain some elementary steps in the arylation of 2‐(aryl)quinazoline halidoruthenacycles.