The preparation, structure, and chemistry of hypervalent iodine compounds are reviewed with emphasis on their synthetic application. Compounds of iodine possess reactivity similar to that of transition metals, but have the advantage of environmental sustainability and efficient utilization of natural resources. These compounds are widely used in organic synthesis as selective oxidants and environmentally friendly reagents. Synthetic uses of hypervalent iodine reagents in halogenation reactions, various oxidations, rearrangements, aminations, C–C bond-forming reactions, and transition metal-catalyzed reactions are summarized and discussed. Recent discovery of hypervalent catalytic systems and recyclable reagents, and the development of new enantioselective reactions using chiral hypervalent iodine compounds represent a particularly important achievement in the field of hypervalent iodine chemistry. One of the goals of this Review is to attract the attention of the scientific community as to the benefits of...

Advances in Synthetic Applications of Hypervalent Iodine Compounds

Hypervalent iodine compounds are privileged reagents in organic synthesis because of their exceptional reactivity. Among these compounds, cyclic derivatives stand apart because of their enhanced stability. They have been widely used as oxidants, but their potential for functional-group transfer has only begun to be investigated recently. The use of benziodoxol(on)es for trifluoromethylation (Togni's reagents) is already widely recognized, but other transformations have also attracted strong interest recently. In this Review, the development in the area since 2011 will be presented. After a short summary of synthetic methods to prepare benziodoxol(on)e reagents, their use to construct carbon-heteroatom and carbon-carbon bonds will be presented. In particular, the introduction of alkynes by using ethynylbenziodoxol(on)e (EBX) reagents has been highly successful. Breakthroughs in the introduction of alkoxy, azido, difluoromethyl, and cyano groups will also be described.

Cyclic Hypervalent Iodine Reagents for Atom-Transfer Reactions: Beyond Trifluoromethylation.

3-NITROPROPIONIC ACID IS A SUICIDE INHIBITOR OF MITOCHONDRIAL RESPIRATION THAT, UPON OXIDATION BY COMPLEX II, FORMS A COVALENT ADDUCT WITH A CATALYTIC-BASE ARGININE IN THE ACTIVE SITE OF THE ENZYME*. Li-shar Huang 1 , Gang Sun 2± , David Cobessi 1§ , Andy Wang 1 , John T. Shen 1 , Eric Y. Tung 1 , Vernon E. Anderson 2 , and Edward A. Berry 1 From Lawrence Berkeley National Laboratory, Berkeley, CA; and , 2 Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, OH Running title: Structure of 3-nitropropionate - inactivated Complex II Address correspondence regarding the crystallographic work to EAB (EABerry@LBL.gov; telephone 1-510-486-4335), and correspondence regarding characterization of the tryptic fragments and 3-NP adduct to VEA (vea@cwru.edu). Current address: Div. of Bioorganic Chemistry and Mol. Pharm., Dept. of Int. Medicine, Wash. Univ. School of Medicine, Campus Box 8020, 660 South Euclid Avenue, St. Louis, MO 63110 Current address: Ecole Superieure de Biotechnologie de Strasbourg, UMR7100 CNRS, Boulevard Sebastien Brant, BP 10413, 67412 Illkirch, France We report three new structures of mitochondrial respiratory Complex II (succinate ubiquinone oxidoreductase, E.C. 1.3.5.1) at up to 2.1 A resolution, with various inhibitors. The structures define the conformation of the bound inhibitors and suggest the residues involved in substrate binding and catalysis at the dicarboxylate site. In particular they support the role of Arg297 as a general base catalyst accepting a proton in the dehydrogenation of succinate. The dicarboxylate ligand in oxaloacetate-containing crystals appears to be the same as that reported for Shewanella flavocytochrome c treated with fumarate. The plant and fungal toxin 3-nitropropionic acid, an irreversible inactivator of succinate dehydrogenase, forms a covalent adduct with the side chain of Arg297. The modification eliminates a trypsin cleavage site in the flavoprotein, and tandem mass spectroscopic analysis of the new fragment shows the mass of Arg 297 to be increased by 83 Da and to have potential of losing 44 Da, consistent with decarboxylation, during fragmentation. The toxin 3-nitropropionic acid (3-NP 1 ) is produced by certain plants and fungi. It is a specific inhibitor of mitochondrial respiratory complex II. Fatalities after eating moldy sugarcane have been linked to 3-NP toxicity(1,2). Ruminants grazing in regions with 3-NP-producing plants acquire resistance due to reduction of the nitro group to an amine by ruminal bacteria(3). The effectiveness of 3-NP in vivo after injection or oral administration has made it useful in studies involving tissues or whole animals. Ingestion of 3-NP results in neurodegeneration with symptoms resembling those of Huntington's disease(4), and conversely Huntington's disease results in loss of complex II activity(5), thus 3-NP has been used to produce an animal model for study of Huntington's(6,7). Symptoms also include convulsions, and 3-NP is being looked at for inducing a model of epilepsy(8). Prior sub- acute 3-NP poisoning seems to provide resistance to ischemic damage to nervous tissue by a preconditioning effect(9) similar to that resulting from mild ischemia. The target of 3-NP is Complex II, which is both a member of the Krebs tricarboxylic acid cycle (oxidizing succinate to fumarate) and an entry-point for electrons into the respiratory chain at the level of ubiquinol. It consists of a large flavoprotein subunit (FP) containing covalently bound FAD, an iron-sulfur protein (IP) with three different iron-sulfur clusters, and two small membrane anchor subunits (chains C and D) ligating a single low-spin heme of type B. Human genetic defects in the IP subunits or chains C or D lead to

3-Nitropropionic Acid is a Suicide Inhibitor of Mitochondrial Respiration that, Upon Oxidation by Complex II, Forms a Covalent Adduct With a Catalytic Base Arginine in the Active Site of the Enzyme

Hypervalent iodine λ3-benziodoxoles are common electrophilic transfer reagents known for their enhanced stability compared to their non-cyclic analogues. Herein we present data showing that chlorobenziodoxole reacts with two different thiolate nucleophiles (thiocyanate and trifluoromethylthiolate), resulting in the formation of stable thioperoxy complexes rather than the expected benziodoxole derivatives. We further report a revised structure for the earlier described electrophilic trifluoromethylthiolation reagent (1), which was previously believed to contain the benziodoxole framework. Our findings, which are based on a combination of analytical techniques, including the recently introduced crystalline sponge method for X-ray analysis, unambiguously demonstrate that 1 is a thioperoxy compound both in solution and the solid state.

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Structural reevaluation of the electrophilic hypervalent iodine reagent for trifluoromethylthiolation supported by the crystalline sponge method for X-ray analysis.

Preparation of conjugated 1,3-enynes by Rh(III)-catalysed alkynylation of alkenes via C-H activation

Herein, we report a detailed study on the electrophilic alkynylation of cyclic keto esters and amides with ethynylbenziodoxolone (EBX) reagents. The structure and stability of this class of reagents is first described more in details. Differential scanning calorimetry (DSC) experiments showed a strong exothermic decomposition with EBX reagents, leading to guidelines for the safe use of these compounds. The extension of the method to aromatic alkynes and a broad range of benziodoxol(on)e reagents is then reported. Based on our preliminary results using Cinchona-based phase-transfer catalysts, the enantioselective alkynylation of cyclic keto esters could be achieved. Binaphthyl-derived ammonium catalysts developed by Maruoka and co-workers gave the highest asymmetric induction with up to 79% ee for an indanone-derived keto ester. Throughout this work, asymmetric induction was observed only in the case of benziodoxolone reagents, demonstrating their superiority over conventional alkynyliodonium salts. The deeper understanding gained about the factors leading to higher asymmetric induction will be very useful in the future to develop a truly general and highly enantioselective alkynylation method.

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Ethynylbenziodoxolones (EBX) as Reagents for the Ethynylation of Stabilized Enolates

Compounds of the formula (I), in which the substituents are as defined in claim 1, are suitable for use as nematicides.

4-membered ring carboxamides used as nematicides

The invention relates to pyrrolone compounds of the formula (I), wherein X, R a , R b , R c , R 1 , R 2 and R 3 are as defined in the specification. Furthermore, the present invention relates to processes and intermediates for making compounds of formula (I), to herbicidal compositions comprising these compounds and to methods of using these compounds to control plant growth.

Pyrazolyl pyrrolinones and their use as herbicides

Compounds of formula (I), as defined herein, to processes for preparing them, to pesticidal, in particular insecticidal, acaricidal, molluscicidal and nematicidal compositions comprising them and to methods of using them to combat and control pests such as insect, acarine, mollusc and nematode pests.

Pesticidally active pyrazole derivatives

We report the simultaneous reduction of the 2-position and oxidationof the anomeric position in several protected furanosyl and pyranosylsugar derivatives, mediated through NHC catalysis. This reactionallows the one-step access to highly valuable 2-deoxy-sugars fromabundant 2-oxygenated sugar derivatives.

Régis Jean Georges Mondiere

Papers

Ethynylbenziodoxolones (EBX) as Reagents for the Ethynylation of Stabilized Enolates

4-membered ring carboxamides used as nematicides

Pyrazolyl pyrrolinones and their use as herbicides

Pesticidally active pyrazole derivatives

Organocatalytic Conversionof Ribose and Other Protected Carbohydrate Derivativesinto 2-Deoxy-lactones