Maxime A. Siegler

Cupric superoxo-mediated intermolecular C-H activation chemistry.

The new cupric superoxo complex [LCu(II)(O(2)(•-))](+), which possesses particularly strong O-O and Cu-O bonding, is capable of intermolecular C-H activation of the NADH analogue 1-benzyl-1,4-dihydronicotinamide (BNAH). Kinetic studies indicated a first-order dependence on both the Cu complex and BNAH with a deuterium kinetic isotope effect (KIE) of 12.1, similar to that observed for certain copper monooxygenases.

Synthesis of Functionalizable Boron-Containing π-Electron Materials that Incorporate Formally Aromatic Fused Borepin Rings†

Boron-containing p-electron systems have emerged as exciting subjects in contemporary organic materials chemistry. The strong Lewis acidity of tricoordinate boron has been utilized for the detection of biologically or environmentally relevant anions. 9] Anionic and neutral boron heteroaromatic molecules are important p-donor ligands for organometallics, and the aromaticity of boroncontaining molecules has inspired substantial experimental and theoretical investigations, thus suggesting that the heteroaromaticity of boron will play will play a key role in other areas where polarization may need to distort p-electron frameworks, such as during operation in electronic devices. The vast majority of boron-based p-electron materials was built with mainchain or lateral 18, 19] tricoordinate boron substitution or from locally antiaromatic four-p-electron fragments such as the borole nucleus within 9-borafluorene. Herein, we present the syntheses and characterization of polycyclic aromatic molecules built around the neutral and formally aromatic six-p-electron borepin ring system that is structurally poised for synthetic elaboration into complex molecular structures. The dibenzo[b,f]borepin (DBB) framework continues to attract substantial attention. 22] Van Tamelen et al. reported the first isolation of DBB as its ethanolamine adduct, and Piers and co-workers very recently reported a B-mesityl DBB that slowly oxidized under ambient conditions. Theoretical studies have revealed planarity throughout the B-H DBB; thus planarity was attractive to us as a means to enhance p-electron delocalization, and nucleus-independent chemical shift (NICS) values reveal a weak degree of aromatic character within the borepin ring of benzo-annelated molecules. However, no synthetic routes for robust and stable tricoordinate borepins that could be tailored into complex p-electron systems have been reported to date. The synthesis of the parent compound DBB 1a is shown in Scheme 1. The stilbene precursor 2a was constructed by a Wittig-type process using reactants derived from a-bromo-o-

Direct, Catalytic Monofluorination of sp3 C–H Bonds: A Radical-Based Mechanism with Ionic Selectivity

Recently, our group unveiled a system in which an unusual interplay between copper(I) and Selectfluor effects mild, catalytic sp(3) C-H fluorination. Herein, we report a detailed reaction mechanism based on exhaustive EPR, (19)F NMR, UV-vis, electrochemical, kinetic, synthetic, and computational studies that, to our surprise, was revealed to be a radical chain mechanism in which copper acts as an initiator. Furthermore, we offer an explanation for the notable but curious preference for monofluorination by ascribing an ionic character to the transition state.

Base-Free Production of H2 by Dehydrogenation of Formic Acid Using An Iridium–bisMETAMORPhos Complex

Erase the base: An iridium complex based on a cooperative ligand that functions as an internal base is reported. This complex can rapidly and cleanly dehydrogenate formic acid in absence of external base, a reaction that is required if formic acid is to be exploited as an energy carrier (see scheme).

Discovery of the Aggregation Pheromone of the Brown Marmorated Stink Bug (Halyomorpha halys) through the Creation of Stereoisomeric Libraries of 1‑Bisabolen-3-ols

We describe a novel and straightforward route to all stereoisomers of 1,10-bisaboladien-3-ol and 10,11-epoxy-1-bisabolen-3-ol via the rhodium-catalyzed asymmetric addition of trimethylaluminum to diastereomeric mixtures of cyclohex-2-enones 1 and 2. The detailed stereoisomeric structures of many natural sesquiterpenes with the bisabolane skeleton were previously unknown because of the absence of stereoselective syntheses of individual stereoisomers. Several of the bisabolenols are pheromones of economically important pentatomid bug species. Single-crystal X-ray crystallography of underivatized triol 13 provided unequivocal proof of the relative and absolute configurations. Two of the epoxides, (3S,6S,7R,10S)-10,11-epoxy-1-bisabolen-3-ol (3) and (3R,6S,7R,10S)-10,11-epoxy-1-bisabolen-3-ol (4), were identified as the main components of a male-produced aggregation pheromone of the brown marmorated stink bug, Halyomorpha halys, using GC analyses on enantioselective columns. Both compounds attracted female, male, and nymphal H. halys in field trials. Moreover, mixtures of stereoisomers containing epoxides 3 and 4 were also attractive to H. halys, signifying that the presence of additional stereoisomers did not hinder attraction of H. halys and relatively inexpensive mixtures can be used in monitoring, as well as control strategies. H. halys is a polyphagous invasive species in the U.S. and Europe that causes severe injury to fruit, vegetables, and field crops and is also a serious nuisance pest.

O2 Activation by Bis(imino)pyridine Iron(II)-Thiolate Complexes

The new iron(II)-thiolate complexes [((iPr)BIP)Fe(II)(SPh)(Cl)] (1) and [((iPr)BIP)Fe(II)(SPh)(OTf)] (2) [BIP = bis(imino)pyridine] were prepared as models for cysteine dioxygenase (CDO), which converts Cys to Cys-SO(2)H at a (His)(3)Fe(II) center. Reaction of 1 and 2 with O(2) leads to Fe-oxygenation and S-oxygenation, respectively. For 1 + O(2), the spectroscopic and reactivity data, including (18)O isotope studies, are consistent with an assignment of an iron(IV)-oxo complex, [((iPr)BIP)Fe(IV)(O)(Cl)](+) (3), as the product of oxygenation. In contrast, 2 + O(2) results in direct S-oxygenation to give a sulfonato product, PhSO(3)(-). The positioning of the thiolate ligand in 1 versus 2 appears to play a critical role in determining the outcome of O(2) activation. The thiolate ligands in 1 and 2 are essential for O(2) reactivity and exhibit an important influence over the Fe(III)/Fe(II) redox potential.

Catalyst selection based on intermediate stability measured by mass spectrometry

The power of natural selection through survival of the fittest is natures ultimate tool for the improvement and advancement of species. To apply this concept in catalyst development is attractive and may lead to more rapid discoveries of new catalysts for the synthesis of relevant targets, such as pharmaceuticals. Recent advances in ligand synthesis using combinatorial methods have allowed the generation of a great diversity of catalysts. However, selection methods are few in number. We introduce a new selection method that focuses on the stability of catalytic intermediates measured by mass spectrometry. The stability of the intermediate relates inversely to the reactivity of the catalyst, which forms the basis of a catalyst-screening protocol in which less-abundant species represent the most-active catalysts, ‘the survival of the weakest’. We demonstrate this concept in the palladium-catalysed allylic alkylation reaction using diphosphine and IndolPhos ligands and support our results with high-level density functional theory calculations. Identifying the best catalyst for a particular reaction traditionally involves testing a wide variety of metal and ligand combinations in standard reactions. Here, the best catalyst is found by using mass spectrometry to identify the least stable — and thus most reactive — intermediate in a dynamic mixture of complexes.

N‐Acetylmethionine and Biotin as Photocleavable Protective Groups for Ruthenium Polypyridyl Complexes

Over the last decades the large therapeutic success of cisplatin-like anticancer drugs, combined to its recognized limitations (such as acquired resistance and general toxicity), have stimulated the scientific community to find other metal-based drugs with anticancer properties. Ruthenium-based molecules, and among them those containing polypyridyl ligands, have emerged as a vast family of active compounds. However, clinical studies have shown that general toxicity remains an important issue, and ruthenium-based chemotherapy is still a heavy burden for the cancer patient. Although several mechanisms might explain their anticancer properties in vivo, the thermal aquation of ruthenium–chloride bonds, followed by coordination to DNA 16–18] and/or proteins is, like for platinum-based anticancer drugs, a highly plausible mode of action (see Figure 1, route 1). 21] However, as thermal breaking of Ru!Cl bonds in aqueous solution might happen anywhere in a human body, this mechanism is thought to be the basis of both antitumor activity and general toxicity. Our analysis that the Ru!Cl coordination bond is too weak to provide good selectivity towards cancer cells, led us to look for protective groups, that is, ligands that would hold more strongly to ruthenium than chlorides, but that could also be cleaved in a controlled way in vivo. In the ideal case, such ligands would avoid the formation of aqua complexes, and thus prevent the coordination of competing biological ligands in vivo. Thioether ligands are ideal candidates because ruthenium(II) likes binding to their soft sulfur atom. Secondly, unlike nitrogen-based ligands, thioethers are only weakly basic in water, which might make their ruthenium complexes less sensitive to pH changes. Finally, visible-light irradiation leads to the controlled release of thioether ligands, which feature might be used to deliver locally the cytotoxic form of the ruthenium complex at the desired location (Figure 1, route 2). The use of light to cure cancer, which has notably led to the clinical development of photodynamic therapy, has also been proposed as an interesting development in metal-based anticancer drug research, in which the presence of oxygen is not required. To investigate this concept, we selected two monodentate thioether ligands of natural origin: N-acetyl-l-methionine and d-biotin, and synthesized their ruthenium complexes [Ru ACHTUNGTRENNUNG(terpy) ACHTUNGTRENNUNG(bpy)(N-acetyl-l-methionine)]Cl2 (compound [3]Cl2) and [RuACHTUNGTRENNUNG(terpy)ACHTUNGTRENNUNG(bpy) ACHTUNGTRENNUNG(d-biotin)]Cl2 (compound [4]Cl2, see Scheme 1). The synthesis is straightforward: it does not require any silver salts to remove the chloride anions, but simply requires mixing in water, at 80 8C and in the dark, the chlorido complex [Ru ACHTUNGTRENNUNG(terpy) ACHTUNGTRENNUNG(bpy)Cl]Cl (compound[1]Cl, see Scheme 1) and one equivalent of the thioether ligand. The course of the reaction can be nicely monitored using H NMR spectroscopy, since each different ruthenium species present in solution gives a distinct A6 [a] R. E. Goldbach, I. Rodriguez-Garcia, S. Bonnet Leiden Institute of Chemistry, Gorlaeus Laboratories Leiden University, P.O. Box 9502 2300 RA Leiden (The Netherlands) E-mail : bonnet@chem.leidenuniv.nl [b] J. H. v. Lenthe Theoretical Chemistry Group Debye Institute for Nanomaterial Science Faculty of Science, Utrecht University Padualaan 8, 3584 CH Utrecht (The Netherlands) [c] M. A. Siegler Small Molecule X-ray Facility Department of Chemistry, Johns Hopkins University Baltimore, MD 21218 (USA) Supporting information for this article (including synthetic procedures, full characterization and high-resolution ES-MS spectra of complexes [3]Cl2 and [4]Cl2; notations for the assignments of the NMR spectra and H NMR spectra; X-ray crystallography resolution method and data; ferrioxalate actinometry, quantum yield measurement procedures, H NMR and kinetic data for irradiation experiments; calculation procedure and x,y,z coordinates for the DFT-minimized species [3A] , [3B] , [4A], and [4B]) is available on the WWW under http://dx.doi.org/10.1002/chem.201101541. Figure 1. One of the modes of action of ruthenium polypyridyl anticancer drugs (reaction 1), and a new photochemotherapy strategy using analogous complexes “protected” by thioethers ligands and “deprotected” by visible light irradiation (reaction 2).

Redox-Active Ligand-Induced Homolytic Bond Activation†

Coordination of the novel redox-active phosphine-appended aminophenol pincer ligand (PNO(H2) ) to Pd(II) generates a paramagnetic complex with a persistent ligand-centered radical. The complex undergoes fully reversible single-electron oxidation and reduction. Homolytic bond activation of diphenyldisulfide by the single-electron reduced species leads to a ligand-based mixed-valent dinuclear palladium complex with a single bridging thiolate ligand. Mechanistic investigations support an unprecedented intramolecular ligand-to-disulfide single-electron transfer process to induce homolytic SS cleavage, thereby releasing a thiyl (sulfanyl) radical. This could be a new strategy for small-molecule bond activation.

The influence of side chains on the structures and properties of functionalized pentacenes

We investigated substituent-induced variations in microstructure and physical properties of a family of functionalized pentacenes, materials currently of intensive interest for making organic electronic devices such as thin film transistors, to shed light on the complex relationships between functionalization, film formation, stability, and microstructure. In this study, the pentacenes were modified with alkyl acetylene or alkylsilylethynyl groups with systematic variations in the alkyl chain length. With a proper side chain, this modification can effectively disrupt the herringbone packing seen in neat pentacene, promoting face-to-face arrangements between the acene rings and providing solubility in a variety of convenient solvents. Thin films can be readily formed by solution casting from THF, bromobenzene, toluene and other organic solvents. We have investigated the structure and properties of the functionalized pentacenes using UV-vis spectroscopy, hot stage optical microscopy, differential scanning calorimetry, transmission electron microscopy, X-ray and electron diffraction. The materials show regular variations in their thermal behavior, crystal packing and macroscopic properties as the chemistry of the side-group substituent changes.