Rüdiger Bertermann

Preparing (Multi)Fluoroarenes as Building Blocks for Synthesis: Nickel-Catalyzed Borylation of Polyfluoroarenes via C–F Bond Cleavage

The [Ni(IMes)2]-catalyzed transformation of fluoroarenes into arylboronic acid pinacol esters via C-F bond activation and transmetalation with bis(pinacolato)diboron (B2pin2) is reported. Various partially fluorinated arenes with different degrees of fluorination were converted into their corresponding boronate esters.

Novel neutral hexacoordinate silicon(IV) complexes with two bidentate monoanionic benzamidinato ligands

The novel neutral hexacoordinate bis(benzamidinato)silicon(iv) complexes 1-10 (SiN(4)X(2) skeletons; X = F, Cl, Br, C, N, S, Se) were synthesised and characterised by elemental analyses, single-crystal X-ray diffraction (except for 2) and NMR spectroscopy in the solid state and in solution. The dynamic behavior of 1 (SiN(4)Cl(2) skeleton) and 3 (SiN(4)F(2)) was additionally studied by variable-temperature NMR experiments. Compounds 1 and 2 (SiN(4)Br(2)) were obtained by reaction of SiCl(4) and SiBr(4), respectively, with two molar equivalents of the corresponding lithium amidinate. Compound 1 served as the starting material in the syntheses of 3-10, in which the two chloro ligands of 1 were substituted by two (pseudo)halogeno or one bidentate dianionic S,S, S,Se or Se,Se ligand. Compound 4 contains an SiN(4)C(2) skeleton and 5-7 contain an SiN(6) skeleton. With the preparation of 8 (SiN(4)S(2) skeleton), 9 (SiN(4)SSe) and 10 (SiN(4)Se(2)) it could be demonstrated that syntheses of hexacoordinate silicon(iv) complexes with soft chalcogeno ligand atoms are indeed feasible. Compounds 9 and 10 are the first hexacoordinate silicon(iv) complexes with Si-Se bonds.

Neutral Six-Coordinate and Cationic Five-Coordinate Silicon(IV) Complexes with Two Bidentate Monoanionic N,S-Pyridine-2-thiolato(−) Ligands

A series of neutral six-coordinate silicon(IV) complexes (4-11) with two bidentate monoanionic N,S-pyridine-2-thiolato ligands and two monodentate ligands R(1) and R(2) was synthesized (4, R(1) = R(2) = Cl; 5, R(1) = Ph, R(2) = Cl; 6, R(1) = Ph, R(2) = F; 7, R(1) = Ph, R(2) = Br; 8, R(1) = Ph, R(2) = N3; 9, R(1) = Ph, R(2) = NCO; 10, R(1) = Ph, R(2) = NCS; 11, R(1) = Me, R(2) = Cl). In addition, the related ionic compound 12 was synthesized, which contains a cationic five-coordinate silicon(IV) complex with two bidentate monoanionic N,S-pyridine-2-thiolato ligands and one phenyl group (counterion: I(-)). Compounds 4-12 were characterized by elemental analyses, NMR spectroscopic studies in the solid state and in solution, and crystal structure analyses (except 7). These structural investigations were performed with a special emphasis on the sophisticated stereochemistry of these compounds. These experimental investigations were complemented by computational studies, including bonding analyses based on relativistic density functional theory.

Generation of Dicoordinate Boron(I) Units by Fragmentation of a Tetra‐Boron(I) Molecular Square

Reduction of carbene-borane adduct [(cAAC)BBr2 (CN)] (cAAC=1-(2,6-diisopropylphenyl)-3,3,5,5-tetramethylpyrrolidin-2-ylidene) cleanly yielded the tetra(cyanoborylene) species [(cAAC)B(CN)]4 presenting a 12-membered (BCN)4 ring. The analysis of the Kohn-Sham molecular orbitals showed significant borylene character of the BI atoms. [(cAAC)B(CN)]4 was found to reduce two equivalents of AgCN per boron center to yield [(cAAC)B(CN)3 ] and fragmented into two-coordinate boron(I) units upon reaction with IMeMe (1,3,4,5-tetramethylimidazol-2-ylidene) to yield the corresponding tricoordinate mixed cAAC-NHC cyanoborylene. The analogous cAAC-phosphine cyanoborylene was obtained by reduction of [(cAAC)BBr2 (CN)] in the presence of excess phosphine.

Neutral Penta‐ and Hexacoordinate Silicon(IV) Complexes Containing Two Bidentate Ligands Derived from the α‐Amino Acids (S)‐Alanine, (S)‐Phenylalanine, and (S)‐tert‐Leucine

The neutral hexacoordinate silicon(IV) complex 6 (SiO(2)N(4) skeleton) and the neutral pentacoordinate silicon(IV) complexes 7-11 (SiO(2)N(2)C skeletons) were synthesized from Si(NCO)(4) and RSi(NCO)(3) (R = Me, Ph), respectively. The compounds were structurally characterized by solid-state NMR spectroscopy (6-11), solution NMR spectroscopy (6 and 10), and single-crystal X-ray diffraction (8 and 11 were studied as the solvates 8 x CH(3)CN and 11 x C(5)H(12) x 0.5 CH(3)CN, respectively). The silicon(IV) complexes 6 (octahedral Si-coordination polyhedron) and 7-11 (trigonal-bipyramidal Si-coordination polyhedra) each contain two bidentate ligands derived from an alpha-amino acid: (S)-alanine, (S)-phenylalanine, or (S)-tert-leucine. The deprotonated amino acids act as monoanionic (6) or as mono- and dianionic ligands (7-11). The experimental investigations were complemented by computational studies of the stereoisomers of 6 and 7.

Neutral Pentacoordinate Silicon(IV) Complexes with Silicon–Chalcogen (S, Se, Te) Bonds

The neutral pentacoordinate silicon(IV) complexes 1 (SiS2ONC skeleton), 2 (SiSeSONC), 3 (SiTeSONC), 6/9 (SiSe2O2C), 7 (SiSe2S2C), and 8/10 (SiSe4C) were synthesized and structurally characterized by using single-crystal X-ray diffraction and multinuclear solid-state and solution-state (except for 6-9) NMR spectroscopy. With the synthesis of compounds 1-3 and 6-10, it has been demonstrated that pentacoordinate silicon compounds with soft chalcogen ligand atoms (S, Se, Te) can be stable in the solid state and in solution.

New Metal-Only Lewis Pairs: Elucidating the Electronic Influence of N-Heterocyclic Carbenes and Phosphines on the Dative Pt-Al Bond

The synthesis and full characterization of a new heteroleptic N-heterocyclic carbene (NHC)-phosphine platinum(0) complex and formation of its corresponding alane adduct is reported. The influence of the ligands on the Lewis basic properties was studied via multinuclear NMR-spectroscopy, X-ray analyses, and density functional theory (DFT) calculations. Consistently, the effect of changing the halogens upon the Lewis acid properties of aluminum halides was studied by X-ray analysis and DFT calculations.

High‐Affinity, Selective σ Ligands of the 1,2,3,4‐Tetrahydro‐1,4′‐silaspiro[naphthalene‐1,4′‐piperidine] Type: Syntheses, Structures, and Pharmacological Properties

The 1′‐organyl‐1,2,3,4‐tetrahydrospiro[naphthalene‐1,4′‐piperidine] derivatives 1 a–4 a [for which organyl=benzyl (1 a), 4‐methoxybenzyl (2 a), 2‐phenylethyl (3 a), or 3‐methylbut‐2‐enyl (4 a)] are high‐affinity, selective σ1 ligands. The corresponding sila‐analogues 1 b–4 b (replacement of the carbon spirocenter with a silicon atom) were synthesized in multistep syntheses, starting from dichlorodivinylsilane, and were isolated as the hydrochlorides 1 b⋅HCl–4 b⋅HCl. Compounds 1 a⋅HCl–4 a⋅HCl and 1 b⋅HCl–4 b⋅HCl were structurally characterized by NMR spectroscopy (1H, 13C, 29Si) in solution, and the C/Si analogues 3 a⋅HCl and 3 b⋅HCl were studied by single‐crystal X‐ray diffraction. These structural investigations were complemented by computational studies. The σ1 and σ2 receptor affinities of the C/Si pairs 1 a/1 b–4 a/4 b were studied with radioligand binding assays. The σ1 receptor affinity of the silicon compounds 1 b–4 b is slightly higher than that of the corresponding carbon analogues 1 a–4 a. Because affinity for the σ2 receptor is decreased by the C/Si exchange, the σ1/σ2 selectivity of the silicon compounds is considerably improved, indicating that the C→Si switch strategy is a powerful tool for modulating both pharmacological potency and selectivity.

Synthesis and Pharmacological Characterization of Disila-AM80 (Disila-tamibarotene) and Disila-AM580, Silicon Analogues of the RARα-Selective Retinoid Agonists AM80 (Tamibarotene) and AM580

Retinoic acid receptors, which act as heterodimers between either one of three RARs (RARa, b, g) and RXRs (RXRa, b, g), are exciting pharmacological targets for cancer and metabolic disease therapies. Studies of the action of retinoic acid on acute promyelocytic leukemia have converted one of the worst leukemias to one that has a most favorable prognosis and might possibly be fully curable following recent advances in the field. In addition, rexinoids are clinically used for the treatment of refractory T-cell leukemia, and novel treatment paradigms based on single-agent or combinatorial treatment are continuously being developed to exploit the enormous ACHTUNGTRENNUNGcytodifferentiation and apoptogenic potential of retinoids and rexinoids. The medicinal-chemistry approaches taken in this context are attempts to increase ligand potency, functionality (agonist, mixed agonist/antagonist, neutral antagonist, or inverse agonist), and receptor selectivity. In search of highly potent and receptor-selective retinoids, a series of silicon-containing RARand RXR-selective retinoid agonists has been synthesized and pharmacologically characterized in recent years. As part of this research project, we have been interested in the biological properties of the silicon analogues of the RARa-selective retinoid agonists AM80 (tamibaACHTUNGTRENNUNGrotene, 1 a) and AM580 (Ro-40-6055, 2 a), h, j, 6] disila-AM80 (disila-tamibarotene, 1 b) and disila-AM580 (2 b), respectively. In a series of earlier studies, the carbon/silicon switch (sila-substitution) strategy has been demonstrated to be a powerful tool for optimizing the pharmacodynamic and/or pharmacokinetic properties of drugs (for recent reviews on silicon-based drugs, see ref. [7]). In this context, disila-substitution of 1 a (!1 b) and 2 a (!2 b) was also very promising. Here we report on the synthesis of the silicon compounds 1 b and 2 b and the pharmacological characterization of the C/Si pairs 1 a/1 b and 2 a/ 2 b. These studies were performed as part of our systematic ACHTUNGTRENNUNGinvestigations on silicon-based drugs (for recent publications, see ref. [8]). Retinoids and rexinoids, as all other ligands of the nuclear receptor (NR) family, act as ligand-regulated trans-acting transcription factors that bind to cis-acting DNA regulatory elements in the promoter regions of target genes. Conceptually, ligand binding does nothing more than modulate the communication functions of the receptor with the intracellular environment, which entails essentially receptor–protein and receptor–DNA or receptor–chromatin interactions. In this communication network, the receptor serves at the same time as intracellular sensor and regulator of cell/organ functions. Receptors are mediators of the information encoded in the chemical structure of a nuclear receptor ligand, as they interpret this ACHTUNGTRENNUNGinformation in the context of cellular identity and cell physiological status and convert it into a dynamic chain of receptor– protein and receptor–DNA interactions. This interpretation is achieved by the allosteric effects that are exerted by a given (natural or synthetic) ligand on the cognate receptor, which result in two distinct events. The first event is the destabilization of the binding interface between the receptor and the corepressor complex (a complex that comprises among others epigenetically acting transcription-silencing histone deacetylases (HDACs)), which pre-exists on some promoters in the absence of ligands. Interestingly, some inverse agonists stabilize corepressor binding and thus act as superantagonists. 12] The second event is induced by the binding of an agonist to the [a] Prof. Dr. R. Tacke, V. M ller, Dr. M. W. B ttner, W. P. Lippert, Dr. R. Bertermann, Dr. J. O. Daiß Universit t W rzburg, Institut f r Anorganische Chemie Am Hubland, 97074 W rzburg (Germany) Fax: (+ 49) 931-888-4609 E-mail : r.tacke@uni-wuerzburg.de [b] H. Khanwalkar, A. Furst, Dr. C. Gaudon, Dr. H. Gronemeyer Department of Cancer Biology Institut de G n tique et de Biologie Mol culaire et Cellulaire (IGBMC) CNRS/INSERM/ULP B. P. 10142, 67404 Illkirch Cedex, C. U. de Strasbourg (France) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cmdc.200900257: NMR data and elemental analyses for compounds 1 b, 2 b, 5–10, 12, and 14.

Exclusive π Encapsulation of Light Alkali Metal Cations by a Neutral Molecule.

Cation-π interactions are one of the most important classes of noncovalent bonding, and are seen throughout biology, chemistry, and materials science. However, in almost every documented case, these interactions play only a supporting role to much stronger covalent or dative bonds, thus making examples of exclusive cation-π bonding exceedingly rare. In this study, a neutral diboryne molecule is found to encapsulate the light alkali metal cations Li(+) and Na(+) in the absence of a net charge, covalent bonds, or lone-pair donor groups. The resulting encapsulation complexes are, to our knowledge, the first structurally authenticated species in which a neutral molecule binds the light alkali metals exclusively through cation-π interactions.