Jordi Benet-Buchholz

Direct Cupration of Fluoroform

We have found the first reaction of direct cupration of fluoroform, the most attractive CF(3) source for the introduction of the trifluoromethyl group into organic molecules. Treatment of CuX (X = Cl, Br, I) with 2 equiv of MOR (M = K, Na) in DMF or NMP produces novel alkoxycuprates that readily react with CF(3)H at room temperature and atmospheric pressure to give CuCF(3) derivatives. The CuCl and t-BuOK (1:2) combination provides best results, furnishing the CuCF(3) product within seconds in nearly quantitative yield. As demonstrated, neither CF(3)(-) nor CF(2) mediate the Cu-CF(3) bond formation, which accounts for its remarkably high selectivity. The fluoroform-derived CuCF(3) solutions can be efficiently stabilized with TREAT HF to produce CuCF(3) reagents that readily trifluoromethylate organic and inorganic electrophiles in the absence of additional ligands such as phenanthroline. A series of novel Cu(I) complexes have been structurally characterized, including K(DMF)[Cu(OBu-t)(2)] (1), Na(DMF)(2)[Cu(OBu-t)(2)] (2), [K(8)Cu(6)(OBu-t)(12)(DMF)(8)(I)](+) I(-) (3), and [Cu(4)(CF(3))(2)(C(OBu-t)(2))(2)(μ(3)-OBu-t)(2)] (7).

Quantitative Evaluation of Anion–π Interactions in Solution

Anions included: A series of meso-tetraaryl calix[4]pyrrole receptors have been used as a model system to quantify chloride–π interactions in solution (see picture; green balls are chloride ions). The free energy values are generally indicative of a repulsive interaction; their magnitude depends on the substituent on the aromatic ring.

NO-independent stimulators of soluble guanylate cyclase.

SARs around a novel type of guanylate cyclase stimulator which act by a mechanism different from classical NO-donors are described. Several pyrazolopyridinylpyrimidines are shown to relax aortic rings and revealed a long-lasting blood pressure lowering effect in rats after oral application.

[(NHC)CuX] complexes: Synthesis, characterization and catalytic activities in reduction reactions and Click Chemistry. On the advantage of using well-defined catalytic systems

The preparation of three series of [(NHC)CuX] complexes (NHC = N-heterocyclic carbene, X = Cl, Br, or I) is reported. These syntheses are high yielding and only use readily available starting materials. The prepared complexes were spectroscopically and structurally characterized. Notably, two of them present a bridging NHC ligand between two copper centers in the solid state, an extremely rare coordination mode for these ligands. These complexes were then applied to two distinct organic reactions: the hydrosilylation of ketones and the 1,3-dipolar cycloaddition of azides and alkynes. In both transformations, outstanding catalytic systems were found for preparing the corresponding products in excellent yields and short reaction times. Most remarkably, the screening of well-defined systems in the hydrosilylation reaction allowed for the identification of a pre-catalyst previously overlooked since, originally, catalytic species were in situ generated. Under such conditions, major formation of [(NHC)(2)Cu](+) species, inactive in this reduction reaction, occurred instead of the expected copper hydride. These results highlight one of the most important advantages of employing well-defined complexes in catalysis: gaining an improved control of the nature of the catalytically relevant species in the reaction media.

Facile C−H Bond Cleavage via a Proton-Coupled Electron Transfer Involving a C−H···CuII Interaction

The present study provides mechanistic details of a mild aromatic C-H activation effected by a copper(II) center ligated in a triazamacrocylic ligand, affording equimolar amounts of a Cu(III)-aryl species and Cu(I) species as reaction products. At low temperatures the Cu(II) complex 1 forms a three-center, three-electron C-H...Cu(II) interaction, identified by pulse electron paramagnetic resonance spectroscopy and supported by density functional theory calculations. C-H bond cleavage is coupled with copper oxidation, as a Cu(III)-aryl product 2 is formed. This reaction proceeds to completion at 273 K within minutes through either a copper disproportionation reaction or, alternatively, even faster with 1 equiv of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), quantitatively yielding 2. Kinetic studies of both reactions strongly implicate a rate-limiting proton-coupled electron transfer as the key C-H activation step, a mechanism that does not conform to the C-H activation mechanism in a Ni(II) analogue or to any previously proposed C-H activation mechanisms.

Effects of Metal Coordination Geometry on Stabilization of Human Telomeric Quadruplex DNA by Square-Planar and Square-Pyramidal Metal Complexes

A series of square-planar and square-based pyramidal metal complexes (metal = Ni(2+), Cu(2+), Zn(2+), and V(4+)) with salphen and salen derivatives as ligands have been prepared. The X-ray crystal structures of three of these complexes are reported, giving insight into the geometric properties of the compounds. The interactions of these complexes with duplex and human telomeric quadruplex DNA have been studied by fluorescence resonance energy transfer (FRET), fluorescent intercalator displacement assay, and in one case circular dichroism. These studies have shown the square-planar metal complexes to be excellent quadruplex DNA stabilizers. In addition, FRET competition assays have shown the complexes to have a high degree of selectivity for the DNA quadruplex versus duplex DNA. These studies have allowed us to establish the most important features that metal complexes should have to interact selectively with quadruplex DNA. This will be of value in defining the best strategy to prepare metal complexes as potential anticancer drugs.

Effective chirogenesis in a bis(metallosalphen) complex through host-guest binding with carboxylic acids.

Transfer of chiral information through supramolecular interactions (chirogenesis) has been observed in many natural systems including DNA and proteins, and is nowadays widely used in the development of smart artificial and biomimetic materials. The induction of chirality in bis(metalloporphyrins) for example, has been successfully applied in assigning the absolute configuration of amines, diamines and aminoamides, aminoalcohols and epoxyalcohols, and diols by using a circular dichroism (CD) protocol. Effective chirality transfer with carboxylic acids, however, has proven to be highly difficult, and has only been achieved by using potassium carboxylate salts followed by tedious extractions, or by the addition of a huge excess of substrate to a metal-free host. The low efficiency of chiral induction with these previous methods is mainly due to the relatively weak host–guest interactions with carboxylic acid groups. To overcome this problem, we have designed a bis[Zn(salphen)] complex 1 (salphen = N,N’-phenylenebis(salicylimine)), which, similar to 2,2’-biphenol units, exists in dynamic equilibrium between two chiral conformations (S and R enantiomers; see Scheme 1). We reasoned that the energy barrier of rotation increases upon binding of a ditopic ligand to the Lewis acidic Zn centers. 12] Herein, we demonstrate that 1 binds very strongly with acetic acid and that axial chirality can be effectively induced by exchange for chiral a-substituted carboxylic acids, with the practical advantage that substrate derivatization or use of excessive substrate is not required. Compound 1 was prepared in a single step by reaction of a bis(salicylaldehyde) molecule with two equivalents of a monoimine precursor and Zn(OAc)2 in the presence of pyridine. Subsequent precipitation from MeOH afforded the product in excellent yield (73 %) and purity (see the Supporting Information). Characterization by NMR spectroscopy indicated the presence of one equivalent of acetic acid, which had formed as a by-product in the synthesis. Slow evaporation of a solution of the product in toluene/ MeCN 1:1 resulted in single crystals suitable for X-ray analysis (Figure 1). The solid-state structure revealed that the two Zn centers of 1 are bridged by AcOH (through the oxygen atoms of the carboxylic acid unit) to give a complex with 1:1 stoichiometry (1 AcOH). As anticipated, both the S and the R conformer were present in a 1:1 ratio in the unit cell; each conformer has the same dihedral angle (44.98) and Zn–O(acetate) distance (2.01 ). This distance is identical to that previously found in a related acetate-bridged complex. Since the exact position of the acidic proton of AcOH could not be resolved by X-ray diffraction, the proton was placed in Scheme 1. Conformational isomerism of 1. The tBu groups are omitted for clarity in the line drawings of the conformers. P denotes righthandedness and M left-handedness.

Shape-persistent octanuclear zinc salen clusters: synthesis, characterization, and catalysis.

We describe a selective and template-controlled synthesis of a series of Zn(8) metal complexes based on a bis-nucleating salen ligand scaffold. Our results, a combination of X-ray analysis and solution studies, show that discrete, shape-persistent metal clusters can be prepared in high yield. Their activity in organic carbonate catalysis is a function of the metal-connecting fragment present in the exterior of the cluster complex. The high stability of the clusters has been confirmed by (1)H, (13)C (DEPTQ) and DOSY NMR, gel permeation chromatography, high-performance liquid chromatography, and mass spectrometry.

A Self‐Improved Water‐Oxidation Catalyst: Is One Site Really Enough?

The homogeneous catalysis of water oxidation by transition-metal complexes has experienced spectacular development over the last five years. Practical energy-conversion schemes, however, require robust catalysts with large turnover frequencies. Herein we introduce a new oxidatively rugged and powerful dinuclear water-oxidation catalyst that is generated by self-assembly from a mononuclear catalyst during the catalytic process. Our kinetic and DFT computational analysis shows that two interconnected catalytic cycles coexist while the mononuclear system is slowly and irreversibly converted into the more stable dinuclear system: an extremely robust water-oxidation catalyst that does not decompose over extended periods of time.

Synthesis, Structure, and Reactivity of New Tetranuclear Ru-Hbpp-Based Water-Oxidation Catalysts

The preparation of three new octadentate tetranucleating ligands made out of two Ru-Hbpp-based units [where Hbpp is 3,5(bispyridyl)pyrazole], linked by a xylyl group attached at the pyrazolate moiety, of general formula (Hbpp)(2)-u-xyl (u = p, m, or o) is reported, together with its dinucleating counterpart substituted at the same position with a benzyl group, Hbpp-bz. All of these ligands have been characterized with the usual analytical and spectroscopic techniques. The corresponding tetranuclear ruthenium complexes of general formula {[Ru(2)(trpy)(2)(L)](2)(μ-(bpp)(2)-u-xyl)}(n+) [L = Cl or OAc, n = 4; L = (H(2)O)(2), n = 6] and their dinuclear homologues {[Ru(2)(trpy)(2)(L)](μ-bpp-bz)}(n+) [L = Cl or OAc, n = 2; L = (H(2)O)(2), n = 3] have also been prepared and thoroughly characterized both in solution and in the solid state. In solution, all of the complexes have been characterized spectroscopically by UV-vis and NMR and their redox properties investigated by means of cyclic voltammetry techniques. In the solid state, monocrystal X-ray diffraction analysis has been carried out for two dinuclear complexes {[Ru(2)(trpy)(2)(L)](μ-bpp-bz)}(2+) (L = Cl and OAc) and for the tetranuclear complex {[Ru(2)(trpy)(2)(μ-OAc)](2)(μ-(bpp)(2)-m-xyl)}(4+). The capacity of the tetranuclear aqua complexes {[Ru(2)(trpy)(2)(H(2)O)(2)](2)(μ-(bpp)(2)-u-xyl)}(6+) and the dinuclear homologue {[Ru(2)(trpy)(2)(H(2)O)(2)](μ-bpp-bz)}(3+) to act as water-oxidation catalysts has been evaluated using cerium(IV) as the chemical oxidant in pH = 1.0 triflic acid solutions. It is found that these complexes, besides generating significant amounts of dioxygen, also generate carbon dioxide. The relative ratio of [O(2)]/[CO(2)] is dependent not only on para, meta, or ortho substitution of the xylylic group but also on the concentration of the starting materials. With regard to the tetranuclear complexes, the one that contains the more sterically constrained ortho-substituted ligand generates the highest [O(2)]/[CO(2)] ratio.