1,2,4,5-Tetrazines have become extremely useful tools in chemical biology. However, the synthesis of some challenging substrates such as 3,6-dialkyl-1,2,4,5-tetrazines is still a limitation for the widespread use of this class of compounds. Herein we describe an efficient route to these compounds based on the Sonogashira coupling of 3-bromo-6-methyl-1,2,4,5-tetrazine with terminal alkynes. The preparation of the starting reagent has been also optimized. The alkynyl products have been used as intermediates for the synthesis of dialkyl-tetrazines through a sequence of hydrogenation and re-oxidation with unprecedented yields. The synthetic applicability of this new approach is showcased through the preparation of several unnatural amino acids bearing alkynyl- and alkyl-1,2,4,5-tetrazine fragments.

The preparation of shelf-stable crystalline salts of tert-butylmethylphosphinous acid borane 1 is described. X-ray analysis of diisopropylammonium tert-butylmethylphosphinite borane 6 revealed the presence of a cyclic hydrogen-bond network in the solid state which accounts for an increased melting point and stability. Dialkylammonium phosphinite boranes are convenient precursors of the chiral tert-butylmethylphosphine fragment. Compound 6 can be used directly in SN2@P reactions with various nucleophiles to yield valuable P-stereogenic intermediates and ligands.

The synthesis of P-stereogenic bisphosphine ligands starting from a phosphinous acid chiral synthon and hydrazine is reported. The dialkylation of the hydrazine backbone yielded atropo- and nitrogen inversion isomers which are in slow exchange. The crystallization of one of the isomers allowed us to study the reaction kinetics of the equilibria. The new ligands were tested in the Rh catalysed asymmetric hydrogenation of various benchmark substrates attaining up to 99% ee.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

The base-stabilized silacyclopropylidene 1 behaves as a versatile strongly nucleophilic ligand toward transition metals. The strong silylene-metal binding related to both increased σ-donating and π-accepting character of silylene 1 compared to N-heterocyclic carbenes (NHCs) allowed the synthesis of robust and air-stable silylene complexes. Of particular interest, the corresponding platinum(0) complex 6 exhibits high stability and a high level of selectivity and catalytic activity in hydrosilylation reactions that is superior to that of the related NHC-Pt(0) complexes.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

A Rh-catalyst system based on the asymmetric ligand (t)Bu2PCH2P(o-C6H4OMe)2 is reported that allows for the hydroacylation of challenging internal alkenes with β-substituted aldehydes. Mechanistic studies point to the stabilizing role of both excess alkene and the OMe-group.

The reaction of a series of imidazolidines with chloro-complexes of Ir, Rh and Ru affords the clean generation of the corresponding monohydrido metal species. Computational analysis of the reduction process suggests that the reaction proceeds via imidazolidine coordination followed by β-hydride elimination, affording the metal hydride and the imidazolinium cation as the only reaction products. The application of imidazolidines for reduction of transition-metal halides represents a principally new method for selective generation of monohydrides. No over-reduction takes place even when using a large excess of the imidazolidine.

A pyracene-linked bis-azolium compound has been obtained from the bis-annulation of tetrakis(iminopyracene) (TIP) with chloromethyl methyl ether. The resulting bis-azolium salt was readily coordinated to rhodium and iridium, affording bis-NHC complexes with 2-fold symmetry. The X-ray structural characterization of the Rh complex containing the pyracenebis(imidazolylidene) ligand is also reported. The new bis-NHC ligand consists of two linearly opposed (Janus-type) imidazolylidenes annulated to both sides of a pyracene skeleton.

Angewandte Chemie International EditionVolume 50, Issue 33 p. 7666-7669 Communication Double CH Bond Activation of C(sp3)H2 Groups for the Preparation of Complexes with Back-to-Back Bisimidazolinylidenes† Amparo Prades, Amparo Prades Departamento de Química Inorgánica y Orgánica, Universitat Jaume I, Avenida Sos Baynat, 12071 Castellón (Spain), Fax: (+34) 96-472-8214Search for more papers by this authorDr. Macarena Poyatos, Dr. Macarena Poyatos Departamento de Química Inorgánica y Orgánica, Universitat Jaume I, Avenida Sos Baynat, 12071 Castellón (Spain), Fax: (+34) 96-472-8214Search for more papers by this authorDr. José A. Mata, Dr. José A. Mata Departamento de Química Inorgánica y Orgánica, Universitat Jaume I, Avenida Sos Baynat, 12071 Castellón (Spain), Fax: (+34) 96-472-8214Search for more papers by this authorProf. Eduardo Peris, Corresponding Author Prof. Eduardo Peris eperis@qio.uji.es Departamento de Química Inorgánica y Orgánica, Universitat Jaume I, Avenida Sos Baynat, 12071 Castellón (Spain), Fax: (+34) 96-472-8214Departamento de Química Inorgánica y Orgánica, Universitat Jaume I, Avenida Sos Baynat, 12071 Castellón (Spain), Fax: (+34) 96-472-8214Search for more papers by this author Amparo Prades, Amparo Prades Departamento de Química Inorgánica y Orgánica, Universitat Jaume I, Avenida Sos Baynat, 12071 Castellón (Spain), Fax: (+34) 96-472-8214Search for more papers by this authorDr. Macarena Poyatos, Dr. Macarena Poyatos Departamento de Química Inorgánica y Orgánica, Universitat Jaume I, Avenida Sos Baynat, 12071 Castellón (Spain), Fax: (+34) 96-472-8214Search for more papers by this authorDr. José A. Mata, Dr. José A. Mata Departamento de Química Inorgánica y Orgánica, Universitat Jaume I, Avenida Sos Baynat, 12071 Castellón (Spain), Fax: (+34) 96-472-8214Search for more papers by this authorProf. Eduardo Peris, Corresponding Author Prof. Eduardo Peris eperis@qio.uji.es Departamento de Química Inorgánica y Orgánica, Universitat Jaume I, Avenida Sos Baynat, 12071 Castellón (Spain), Fax: (+34) 96-472-8214Departamento de Química Inorgánica y Orgánica, Universitat Jaume I, Avenida Sos Baynat, 12071 Castellón (Spain), Fax: (+34) 96-472-8214Search for more papers by this author First published: 29 June 2011 https://doi.org/10.1002/anie.201101806Citations: 42 † We gratefully acknowledge financial support from the MEC of Spain (CTQ2008-04460/BQU) and Bancaixa (P1.1B2010-02, P1.1A2008-02). We also thank the Ramón y Cajal program (M.P.). A.P. thanks the Ministerio de Ciencia e Innovación for a fellowship. We are grateful to the Serveis Centrals d'Instrumentació Científica (SCIC) of the Universitat Jaume I for providing us with spectroscopic and X-ray facilities. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Two-headed carbenes: N-heterocyclic carbene complexes of rhodium and iridium were obtained by the double CH activation of CH2 groups in N heterocycles (see structure: C gray, N blue, Cl green, Ir pink). The reaction constitutes a valuable approach to new carbene ligands with unprecedented architectures. Citing Literature Supporting Information Detailed facts of importance to specialist readers are published as "Supporting Information". Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Filename Description anie_201101806_sm_miscellaneous_information.pdf687.2 KB miscellaneous_information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume50, Issue33August 8, 2011Pages 7666-7669 RelatedInformation

A series of "RuII(η6-arene)" complexes with 1,2,3-triazolylidene ligands have been prepared and fully characterized. The molecular structure of one of the new complexes has been determined by means of X-ray diffractrometry. The new complexes have been tested in a set of catalytic reactions involving alcohols and amines as substrates, including (i) base-free oxidation of benzylic alcohols to benzaldehydes, (ii) homocoupling of amines to form imines, and (iii) oxidative coupling of amines and alcohols to form amides. The results show the high versatility of the catalysts used and illustrate the application potential of 1,2,3-triazolylidene ligands in the design of effective homogeneous catalysts.

A series of (eta(6)-arene)ruthenium complexes have been tested in the arylation of arylpyridines. One (eta(6)-p-cymene)ruthenium(N-heterocyclic carbene) complex (labelled as 1 in the text) was found to be the most effective, being capable of arylating a wide set of substantially different arylpyridines. Complex 1 is also able to promote the regioselective deuteration of a series of arylated N-heterocycles, via a nitrogen-directed mechanism. Two of the deuterated amines were used to measure the kinetic isotope effect (KIE) in the arylation process. The detection of an inverse KIE, together with the observation that the C H activation process does not require the addition of a base, suggest that the rate-limiting step in the arylation process may be different to that of previously reported studies.

N-Heterocyclic carbene (NHC) ligands have attracted great interest over the last decade for their use in the design of homogenous catalysts. NHC-based metal complexes have interesting potential biomedical applications, such as in antimicrobial and cancer therapy, which are beginning to be explored more fully. We have studied here the oxidant activities of a series of Ru(II) complexes in vitro and zebrafish (Danio rerio) have been used as a model in vivo to investigate and characterize the toxicity of some of these compounds. Dual behavior was observed for the NHC-based complexes as they behaved as antioxidants at low concentrations but showed pro-oxidant capacity at higher concentrations. Zebrafish embryos were exposed to Ru(II) complexes under several different conditions (0 or 24 h postfertilization, with or without the chorion) and various parameters, such as viability, edema, heart rate, blood coagulation, pigmentation, scoliosis, malformation, and hatching, were tested. In general, zebrafish embryos were not harmed by exposure to Ru(II) complexes whatever the experimental conditions. Several toxicity profiles were observed depending upon the chemical structure of the compound in question. Their characteristics as pro-oxidant and/or antioxidant agents together with their biosafety may point to their having biomedical applications as antitumoral or neuroprotective drugs.

One catalyst fits all! One catalyst is active for a wide set of benzylating reactions (see scheme). A tandem process allows the use of aldehydes and ketones as benzylating agents.The compound [IrCp*(OTf)(2)(I(nBu))] (I(nBu)=1,3-di-n-butyl-imidazolylidene) is an effective catalyst in the benzylation of arenes with different benzylating agents, such as alcohols, ethers and styrenes, representing an unprecedented highly versatile catalyst for this type of process. The same compound also catalyses a remarkable tandem process that allows the use of aldehydes and ketones as benzylating agents, through the base-free hydrogenation of C==O bonds with iPrOH and further use of the resulting primary or secondary alcohols as benzylating agents.

A comparative study on the catalytic activity of a series of [IrCl(2)Cp*(NHC)] complexes in several C-O and C-N coupling processes implying hydrogen-borrowing mechanisms has been performed. The compound [IrCl(2)Cp*(I(nBu))] (Cp*=pentamethyl cyclopentadiene; I(nBu)=1,3-di-n-butylimidazolylidene) showed to be highly effective in the cross-coupling reactions of amines and alcohols, providing high yields in the production of unsymmetrical ethers and N-alkylated amines. A remarkable feature is that the processes were carried out in the absence of base, phosphine, or any other external additive. A comparative study with other known catalysts, such as Shvo's catalyst, is also reported.

A series of five different "(p-cymene)Ru(NHC)" complexes (NHC = imidazolin-2-ylidene, imidazolin-4-ylidene, and pyrazolin-3-ylidene) have been obtained and fully characterized. The crystal structure of two of the new complexes has been determined by X-ray diffraction methods. All five complexes have been tested in the catalytic beta-alkylation of secondary alcohols with primary alcohols and the dimerization of phenyl acetylene, showing an excellent activity in both processes. A clear improvement on the catalytic activity of the complexes is observed when the more basic NHC ligands are used. The pyrazolylidene-Ru complex lies among the best catalysts for the beta-alkylation of secondary alcohols reported to date.