“All new is well-forgotten old”, the proverb goes. The current “fluorine boom” is news only to a novice in the field: the exceptional importance of fluorinated organic compounds in numerous areas has been known for a long time. The sharpest increase in the number of fluorine-containing pharmaceuticals and agrochemicals is dated back to 30 years ago. Also around that time (1979), the first monograph devoted to industrial applications of organofluorine compounds was published, covering not only fluorine-containing biologically active materials but also refrigerants, propellants, surfactants, textile chemicals, polymers, and dyes. The increasingly broad realization of the key role of organofluorine compounds in numerous areas has recently attracted many new scientists to the field. The development of new methods for the selective introduction of fluorine and fluorinecontaining groups into organic molecules for biologically active and other useful materials has become a hot area. Over 100 reviews, book chapters, and highlights on this subject have appeared in the literature in the past few years. As citing all of these publications in this review article is impossible, we provide references to only the most recent, general, and comprehensive ones. Molecules bearing a trifluoromethyl group constitute one of the most important classes of selectively fluorinated compounds. As early as 1928, Lehmann reported his observations of biological activity of some trifluoromethylated organic derivatives and already in 1959 Yale published a detailed review article entitled “The Trifluoromethyl Group in Medicinal Chemistry”. Since then, numerous books and reviews have appeared in the literature covering various aspects of trifluoromethylated organic and organometallic compounds. Within this family, derivatives bearing the CF3 group on aromatic rings are particularly numerous and important. Some examples of such compounds used as active ingredients of pharmaceuticals and agrochemicals are shown in Scheme 1. Trifluoromethylated building blocks and intermediates are clearly needed to make such molecules. The simplest trifluoromethylated aromatic compound, benzotrifluoride, was originally prepared by Swarts at the end of the 19th century. In his work, Swarts treated benzotrichloride with “two thirds of its weight of antimony fluoride” to obtain a mixture of PhCF2Cl and PhCF3, from which the two were separated and isolated pure by distillation. In the early 1930s, two industrial groups, one from Kinetic Chemicals, Inc. and one from I. G. Farbenindustrie AG patented their discoveries on the successful use of HF instead of SbF3 for the Swarts reaction. These inventions were the starting point for the modern large-scale manufacturing of trifluoromethylated aromatics. Other methods have been developed for conversion of various C1 units on the ring to CF3 with a variety of fluorinating agents. While representing an outstanding discovery and a classic of organic and organofluorine chemistry, the Swarts reaction is nonetheless neither atom-economical nor environmentally benign, as it deals with stoichiometric quantities of hazardous chemicals and generates large amounts of chlorine waste. To convert a CH3 group on the ring to CF3, the methyl is first exhaustively chlorinated to produce 3 equiv of HCl as a

Aromatic Trifluoromethylation with Metal Complexes

Sulfoxides are capable of forming stable complexes with transition metals and there have been many comprehensive studies into their binding properties. However, the use of sulfoxides, particularly chiral sulfoxides, as ligands in transition metal catalysis is rather less well developed. This review aims to describe these catalytic studies and covers new developments that are showing very promising results and that have led to a renewed interest in this field.

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The emergence of sulfoxides as efficient ligands in transition metal catalysis.

A series of new organometallic platinum(II) complexes containing terdentate polypyridine ligands has been prepared and characterized. Their absorption spectra in 4:1 (v/v) MeOH/EtOH fluid solution at room temperature and luminescence in the same matrix at 77 K have been investigated. The new species are [Pt(terpy)Ph]Cl (3, terpy = 2,2‘:6‘,2‘‘-terpyridine, Ph = phenyl), [Pt(Ph-terpy)Cl]Cl (4, Ph-terpy = 4‘-phenyl-2,2‘:6‘,2‘‘-terpyridine), [Pt(Ph-terpy)Me]Cl (5), and [Pt(Ph-terpy)Ph]Cl (6). The results have been compared with those for [Pt(terpy)Cl]Cl (1) and [Pt(terpy)Me]Cl (2). NMR data evidence that all the complexes but 3 and 6 oligomerize in solution leading to stacked species. The absorption spectra are dominated by moderately intense metal-to-ligand charge-transfer (MLCT) bands in the visible region and by intense ligand-centered (LC) bands in the UV region. All the compounds are luminescent in a 4:1 (v/v) MeOH/EtOH rigid matrix at 77 K, exhibiting a structured emission within the range 460−600 nm. T...

Synthesis, Characterization, Absorption Spectra, and Luminescence Properties of Organometallic Platinum(II) Terpyridine Complexes

In the search for new therapeutic tools against American Trypanosomiasis palladium complexes with bioactive nitrofuran-containing thiosemicarbazones as ligands were obtained. Sixteen novel palladium (II) complexes with the formulas [PdCl2(HL)] and [Pd(L)2] were synthesized, and the crystal structure of [Pd(5-nitrofuryl-3-acroleine thiosemicarbazone)2] x 3DMSO was solved by X-ray diffraction methods. Most complexes showed higher in vitro growth inhibition activity against Trypanosoma cruzi than the standard drug Nifurtimox. In most cases, the activity of the ligand was maintained or even increased as a result of palladium complexation. In addition, the complexes' mode of antitrypanosomal action was investigated. Although the complexes showed strong DNA binding, all data strongly suggest that the main trypanocidal mechanism of action is the production of oxidative stress as a result of their bioreduction and extensive redox cycling. Moreover, the complexes were found to be irreversible inhibitors of trypanothione reductase.

Novel antitrypanosomal agents based on palladium nitrofurylthiosemicarbazone complexes: DNA and redox metabolism as potential therapeutic targets.

Structure and activity relationships of platinum complexes with anti-tumour activity.

Palladium(II) and platinum(II) alkyl sulfoxide complexes. Examples of sulfur-bonded, mixed sulfur- and oxygen-bonded, and totally oxygen-bonded complexes

Reaction of Pd(TMEDA)(CH(3))(2) [TMEDA = tetramethylethylenediamine] with fluoroalkyl iodides R(F)I affords a series of square planar Pd(II) complexes Pd(TMEDA)(CH(3))(R(F)) [R(F) = CF(2)CF(3) (9), CFHCF(3) (10), CH(2)CF(3) (11)], presumably by oxidative addition followed by reductive elimination of CH(3)I. The solid-state structures of each compound have been determined by single crystal X-ray diffraction studies, allowing the effect of increasing alpha-fluorination on the structural trans-influence of alkyl ligands to be examined. In these compounds there is no significant difference observed in the trans-influence of the three fluorinated alkyl ligands toward the trans-N atom, although a significant cis-influence on the neighboring methyl ligand is apparent. Oxidative addition of the same series of fluoroalkyl ligands to the corresponding Pt(TMEDA)(CH(3))(2) affords octahedral Pt(IV) complexes trans-Pt(TMEDA)(CH(3))(2)(R(F))I [R(F) = CF(2)CF(3) (12), CFHCF(3) (13), CH(2)CF(3) (14)] as the kinetic products. In each case, subsequent isomerization to the corresponding all cis-isomers is observed; in the case of 13, the stereocenter at the alpha-carbon results in two diastereomeric cis-isomers, which are formed at different rates. The molecular structures of 13 and its more stable all cis-isomer 16b have been crystallographically determined. Kinetic studies of the trans-cis isomerization reactions show the mechanism to involve a polar transition state, presumably involving iodide dissociation, followed by rearrangement of the cation, and iodide recombination. High dielectric solvents increase the rate, but solvent coordinating ability has no effect. Dissolved salts (LiI, LiOTf) show normal accelerative salt effects, with no inhibition in the case of added iodide, consistent with the formation of an intimate ion pair intermediate. The kinetic parameters show that the trans-effects of fluoroalkyl ligands in these compounds follow the order expected from the relative sigma-donor properties of the ligands, with CF(2)CF(3) < CFHCF(3) < CH(2)CF(3).

Does α-fluorination affect the structural trans-influence and kinetic trans-effect of an alkyl ligand? molecular structures of Pd(TMEDA)(CH3)(RF) and a kinetic study of the trans to cis isomerization of Pt(TMEDA)(CH3)2I(RF) [RF = CF2CF3, CFHCF3, CH2CF3]

Palladium(ii)- und platin(ii)-alkylsulfoxidkomplexe, beispiele fuer schwefelgebundene, gemischte schwefel- und sauerstoffgebundene und vollstaendig sauerstoffgebundene komplexe

Alex N. Williamson

Papers

Palladium(II) and platinum(II) alkyl sulfoxide complexes. Examples of sulfur-bonded, mixed sulfur- and oxygen-bonded, and totally oxygen-bonded complexes

Does α-fluorination affect the structural trans-influence and kinetic trans-effect of an alkyl ligand? molecular structures of Pd(TMEDA)(CH3)(RF) and a kinetic study of the trans to cis isomerization of Pt(TMEDA)(CH3)2I(RF) [RF = CF2CF3, CFHCF3, CH2CF3]

Palladium(ii)- und platin(ii)-alkylsulfoxidkomplexe, beispiele fuer schwefelgebundene, gemischte schwefel- und sauerstoffgebundene und vollstaendig sauerstoffgebundene komplexe