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The alternative method allows a precise control of the critical cyanide concentration in solution by variation of the dosage rate.

A detailed investigation into the influence of phosphines, additives, bases and solvents on the Heck coupling reaction of 4-trifluoromethyl-1-chlorobenzene (2) is presented. It is shown that a number of catalyst systems exist for efficient cross coupling of electron-deficient aryl chlorides with various olefins. Basicity and steric demand of the ligand are two factors which determine the success of the reaction. In addition the phosphine/palladium ratio, the correct type and amount of additive, and finally the use of an appropriate base and solvent are also important. The optimised reaction conditions are applied for the arylation of styrene, 2-ethylhexyl acrylate and N,N-dimethyl acrylic amide with various aryl chlorides.

Non- and deactivated chloroarenes can be coupled with a wide range of ketones to yield the corresponding arylmethyl ketones in good to excellent yields using a palladium(II) acetate/n-BuPAd2 catalyst system. Depending on the ketone, the chloroarene/ketone ratio and the base, mono or diarylation can be effected selectively.

During the last decade several palladium-catalyzed reactions have been developed and optimized to a stage that enables application on an industrial scale. The importance of these reactions as novel key steps for fine chemical synthesis is shown. Examples include palladium-catalyzed Heck, Suzuki and Sonogashira coupling reactions, telomerization of 1,3-butadiene with nucleophiles, and carbonylation of aromatic and benzylic halides.

An improved protocol for the palladium-catalyzed cyanation of electron-rich aryl chlorides with potassium ferrocyanide {K 4 [Fe(CN) 6 ]} is presented. Compared to previous procedures the substrate scope is significantly broadened.

A direct, intermolecular addition of 1,3-dicarbonyl compounds to styrenes in the presence of FeCl3 as an inexpensive and disposable catalyst has been developed for the straightforward and practical synthesis of arylated diketones and ketoesters. The reactions proceed under mild conditions for most substrates (50-80 degrees C), and no strong acid or base is required. The synthetic value of the method is demonstrated by 15 examples, including the synthesis of the current pharmaceutical drug warfarin in one step and 42% yield from commercially available substrates.

Various CH-acidic 1,3-dicarbonyl compounds and methyl 3-acetamidobut-2-enoate react with benzylic alcohols to give the corresponding 2-benzylated products in good to excellent yield. Typically, reactions proceed under mild conditions (50–80 °C; air) in the presence of catalytic amounts of inexpensive iron chloride hexahydrate. The benzylation of 4-hydroxycoumarin gives the pharmaceutically interesting 4-hydroxy-3-(1-phenylethyl)-2H-chromen-2-ones. As an example the anticoagulant Phenprocoumon is prepared in one step from commercially available substrates in 94 % yield.

Benzonitriles are easily accessible via palladium-catalyzed cyanation of aryl halides using potassium hexacyanoferrate(II) as cyanide source. This method is applicable on both activated and deactivated aryl and heteroaryl bromides and activated chlorides giving the corresponding benzonitriles in good to excellent yield. Advantageously, the used cyanating agent is non-toxic and cheap. The presented catalyst system is rather simple and it is not necessary to add expensive phosphines, making the novel method also attractive for industrial applications.

The palladium-catalyzed cyanation of aryl halides is an elegant method for the preparation of benzonitriles. Since its discovery in 1973, this reaction has been the topic of several investigations. Nevertheless, the general methodology is still somewhat underdeveloped compared to other palladium-catalyzed coupling reactions. Here, we summarize important developments from 1997 until 2003 in this area. Recent contributions from our group include the development of palladium/phosphane/amine catalyst systems for the cyanation of aryl chlorides, the successful cyanation of aryl halides with acetone cyanohydrin and trimethylsilyl cyanide as cyanation reagents, and a general improvement of catalyst efficiency by using a continuous dosage of cyanide sources. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)