Aromatic Iodides Research Articles

Oxidative Breakdown of Iodoalkanes to Catalytically Active Iodine Species: A Case Study in the α-Tosyloxylation of Ketones

Catalysis of the oxidative processes by iodoarenes has become a promising direction in synthesis. The mechanism, involving the well-known isolable hypervalent iodine species, is generally limited to aromatic iodides, since the corresponding aliphatic species are normally highly unstable. Nevertheless, in this work catalytic amount of several primary, secondary or tertiary iodoalkanes were found to promotes the α-tosyloxylation of a range of ketones with RSO3H, including aliphatic sulfonates. The process, was found to proceed through the oxidative breakdown of the iodoalkane to an inorganic catalytic species (likely IO− or IO2−), thus falling within the previously described catalysis using molecular iodine or inorganic iodides. The catalyst eventually becomes deactivated through the precipitation of an iodine overoxidation product, the structure of which was solved ab initio from the powder diffraction data as a hitherto unreported phase of the iodic acid (HIO3).

Natural products in synthesis and biosynthesis

This is the second Thematic Series in the Beilstein Journal of Organic Chemistry focused on natural products. While the first Thematic Series summarized recent research work on the biosynthesis and function of natural products [1–2], the present Thematic Series deals with synthetic and biosynthetic aspects. Why the research interest in natural products? Natural products are structurally fascinating as is spectacularly demonstrated by the prominent examples of maitotoxin [3], the largest non-polymer secondary metabolite known to date, or calicheamycin (Fig. 1), which possibly holds the record in carrying the most diverse functional groups including an enediyne subunit, a deoxysugar, an aminosugar, a hydroxylamine linkage between two sugar subunits, a carbamate, an aromatic iodide, a thioester, and a trisulfide [4]. Natural products have also been used by humankind since ancient times and are part of our traditions and culture, as is evident from the widespread consumption of coffee, tea, tobacco and cocoa, drugs that all contain alkaloids with stimulating effects. More importantly, starting from their usage in traditional medicine natural products – and today also compounds inspired by natural products – are indispensable in the treatment of various threatening infectious diseases. The rapid spreading of antibiotic resistances and the comeback of some infectious diseases already claimed to be eliminated should sharpen our minds for the beneficial roles of natural products in medicine as well as their responsible use. This should be a strong appeal upon the responsibility of both researchers and decision makers in the academic sciences and the pharmaceutical industry. Figure 1 Calicheamycin. Why should we have a look at the synthetic and biosynthetic aspects of natural products in this Thematic Series? Of course, the chemistry of nature and as it is used by chemists is one and the same and makes use of the same intrinsic reactivity of molecules. It is fascinating to see that a particular chemical reaction, believed to be invented by man, is in fact already used for millions – sometimes even billions – of years by Mother Nature. An interesting example is the discovery of the Diels–Alder reaction in the 1920s and its later enhancement into an enantioselective reaction by the development of chiral catalysts. But a Diels–Alder reaction also occurs in the biosynthesis of lovastatin and is likely catalysed by a Diels–Alderase [5], a natural analogue of man-made chiral catalysts! Beyond such fascinating examples of comparing natural to artificial systems it is their interplay that may provide the best solutions to some of the most urgent problems of our time. A perfect example is artemisinin, a terpenoid natural product from Artemisia annua, which is highly efficient in the treatment of malaria. The problem is that the plant produces only small and variable amounts, thereby making the isolation procedure difficult and expensive. Neither biotechnology nor chemistry were able to provide a solution on their own, but the combination of the heterologous production of an advanced intermediate in yeast [6] and its further elaboration by chemical synthesis [7] procures sufficient quantities of artemisinin at a reasonable price. An impressive demonstration of the effectiveness of multi-disciplinary research. I would like to thank the highly professional team of the Beilstein-Institut for a very pleasant cooperation on this Thematic Series. I wish you, the reader, joy and fun with this Thematic Series and – at the best – a new impetus for your own future research! Jeroen S. Dickschat Braunschweig, September 2013

Palladium-catalyzed aminocarbonylation of aryl iodides using aqueous ammonia

Abstract Aminocarbonylation of aromatic iodides using aqueous ammonia in toluene has been developed. Various primary aromatic amides have been efficiently synthesized in good to excellent yields in the presence of catalytic quantities of Pd(OAc) 2 /CYTOP®292. The usage of aqueous ammonia avoids the handling of two gases in the reaction.

Computed CH Acidity of Biaryl Compounds and Their Deprotonative Metalation by Using a Mixed Lithium/Zinc‐TMP Base

With the aim of synthesizing biaryl compounds, several aromatic iodides were prepared by the deprotonative metalation of methoxybenzenes, 3-substituted naphthalenes, isoquinoline, and methoxypyridines by using a mixed lithium/zinc-TMP (TMP=2,2,6,6-tetramethylpiperidino) base and subsequent iodolysis. The halides thus obtained, as well as commercial compounds, were cross-coupled under palladium catalysis (e.g., Suzuki coupling with 2,4-dimethoxy-5-pyrimidylboronic acid) to afford various representative biaryl compounds. Deprotometalation of the latter compounds was performed by using the lithium/zinc-TMP base and evaluated by subsequent iodolysis. The outcome of these reactions has been discussed in light of the CH acidities of these substrates, as determined in THF solution by using the DFT B3LYP method. Except for in the presence of decidedly lower pKa values, the regioselectivities of the deprotometalation reactions tend to be governed by nearby coordinating atoms rather than by site acidities. In particular, azine and diazine nitrogen atoms have been shown to be efficient in inducing the reactions with the lithium/zinc-TMP base at adjacent sites (e.g., by using 1-(2-methoxyphenyl)isoquinoline, 4-(2,5-dimethoxyphenyl)-3-methoxypyridine, or 5-(2,5-dimethoxyphenyl)-2,4-dimethoxypyrimidine as the substrate), a behavior that has already been observed upon treatment with lithium amides under kinetic conditions. Finally, the iodinated biaryl derivatives were involved in palladium-catalyzed reactions.

Copper-Catalyzed N-Arylation of 2-Imidazolines with Aryl Iodides

The first copper-catalyzed N-arylation of 2-imidazolines is described. The reaction affords compounds with desirable lead-like characteristics in high yield with practical simplicity under inexpensive, "ligand-free" conditions. The cross coupling was successful with electron-rich and electron-poor aromatic iodides. Substrates bearing halides, esters, nitriles, and free hydroxyls are well tolerated, providing reactive handles for further functionalization, as are pyridines. In addition, the regioselective N-arylation of a 4-substituted imidazoline is reported.

ChemInform Abstract: Stereospecific Preparation of (E)‐1,2‐Difluoro‐1,2‐disubstituted Alkenes.

Abstractvia Pd‐catalyzed coupling of (Z)‐vinyl stannanes (I) with aromatic iodides (II)

ChemInform Abstract: Copper(I)‐Catalyzed Amination of Aryl Halides in Liquid Ammonia.

AbstractCuI in combination with ascorbic acid promotes the coupling of aromatic iodides and bromides with liquid NH3 and allows selective formation of a number of primary amines in good to high yields.

Understanding the observed decreasing specific activity value in the series: aryl iodide, aryl bromide, aryl chloride during palladium catalyzed tritium dehalogenations

The factors involved in the commonly observed decreasing specific activity value for the series aromatic iodide, aromatic bromide and aromatic chloride during palladium catalyzed tritium dehalogenations are explored.

The stereospecific preparation of (E)-1,2-difluoro-1,2-disubstituted alkenes

(Z)-1,2-difluoro-2-substituted vinyl silanes were prepared stereospecifically from chlorotrifluoroethene, chlorotrimethylsilane and alkyl or aryllithium reagents. Subsequent exchange of the trimethylsilyl group via reaction of the vinylsilane with KF/n-Bu3SnCl/DMF stereospecifically afforded the corresponding (Z)-1,2-difluoro-2-substituted vinyl stannanes. Pd(PPh3)4/Cu(I)I/DMF coupling of the vinyl stannanes with substituted aromatic iodides stereospecifically provided the (E)-1,2-difluoro-1-substituted aryl-alkenes in excellent yield.

Hydroxyl Radical Promotes the Direct Iodination of Aromatic Compounds with Iodine in Water: A Combined Experimental and Theoretical Study

It is still a challenge to develop green, simple and effective approaches to prepare aromatic iodides. Herein, a novel and green strategy for the direct mono-iodination of aromatic compounds starting with molecular iodine has been developed. The strategy uses ceria nanocrystals to decompose hydrogen peroxide, giving hydroxyl radicals which are demonstrated experimentally and computationally to be crucial to promote the iodinations.

A Simple and Effective Protocol for One-Pot Diazotization-Iodination of Aromatic Amines by Acidic Ionic Liquid [H-NMP]HSO4 at Room Temperature

A simple and efficient one-pot method for the preparation of aromatic iodides has been developed by sequential diazotization-iodination of aromatic amines employing sodium nitrite and sodium iodide in the presence of acidic ionic liquid N-methyl-2-pyrrolidonum hydrosulfate ((H-NMP)HSO 4). The diazonium salts that are formed by this ionic liquid are stable at room temperature and react rapidly with sodium iodide to produce aryl iodides in moderate to good yields. The mild reaction conditions, straightforward procedure, inexpensive and green method make these transformations superior to the reported

Water-soluble complexes MX 2L 2 (M = Pd, Pt; L = PPh 2(C 6H 4- p-SO 3K)): Synthesis, stereoisomerism, and catalytic activities for aromatic cyanation in n-heptane/water biphasic solution

Reaction of (COD)MX 2 (M = Pd, Pt; X = Cl, I; COD = 1,5-cyclooctadiene) and P(C 6H 5) 2(C 6H 4- p-SO 3K) afforded water-soluble complexes MX 2{P(C 6H 5) 2(C 6H 4- p-SO 3K)} 2 (M = Pd; X = Cl ( 1), M = Pt; X = Cl ( 2), I ( 3)) in high yields. Complexes 1– 3 were fully characterized by various spectroscopic methods (IR, 1H-, 13C{ 1H}- and 31P{ 1H}-NMR spectroscopy) and elemental analyses. For 1 and 3, a mixture of the cis- and trans-isomer was produced from the reaction. For 2, however, only the cis-isomer was obtained. The stereochemistry of 1– 3 can be assigned by the chemical shifts and the 1 J(Pt–P) values in 31P{ 1H}-NMR spectral data. The ratios of the cis/ trans isomers of 1 and 3 obtained from reactions in a range of solvents with various dielectric constants resulted in a little variation. However, addition of aqueous potassium halide solution to a DMSO- d 6 solution of 1 and 3 considerably increased the ratio of the cis/ trans, respectively, indicating a strong intramolecular interligand Coulombic repulsion between the ionic phosphine ligands is present. Catalytic cyanation of aromatic iodide with KCN/ZnCl 2 in n-heptane/water biphasic system has been tested in the presence of 1– 3 with base.

Thermodynamic properties of organic iodine compounds

A critical evaluation has been made of the thermodynamic properties reported in the literature for 43 organic iodine compounds in the solid, liquid, or ideal gas state. These compounds include aliphatic, cyclic and aromatic iodides, iodophenols, iodocarboxylic acids, and acetyl and benzoyl iodides. The evaluation has been made on the basis of carbon number systematics and group additivity relations, which also allowed to provide estimates of the thermodynamic properties of those compounds for which no experimental data were available. Standard molal thermodynamic properties at 25 °C and 1 bar and heat capacity coefficients are reported for 13 crystalline, 29 liquid, and 39 ideal gas organic iodine compounds, which can be used to calculate the corresponding properties as a function of temperature and pressure. Values derived for the standard molal Gibbs energy of formation at 25 °C and 1 bar of these crystalline, liquid, and ideal gas organic iodine compounds have subsequently been combined with either solubility measurements or gas/water partition coefficients to obtain values for the standard partial molal Gibbs energies of formation at 25 °C and 1 bar of 32 aqueous organic iodine compounds. The thermodynamic properties of organic iodine compounds calculated in the present study can be used together with those for aqueous inorganic iodine species to predict the organic/inorganic speciation of iodine in marine sediments and petroleum systems, or in the near- and far-field of nuclear waste repositories.

Efficient Route to Atropisomeric Ligands – Application to the Synthesis of MeOBIPHEP Analogues

A highly efficient Pd-catalyzed P-C coupling reaction of easily accessible atropisomeric bisphosphane is described in the presence of various electron-poor aromatic iodides. The reactions are conducted in the presence of a Pd(II)/dppf catalyst in acetonitrile at 80 °C. The reaction conditions are compatible with several electron-withdrawing groups such as esters, cyano, chloro, and trifluoromethyl groups and lead to atropisomeric MeOBIPHEP derivatives in good to excellent yields and high enantiomeric purities.

ChemInform Abstract: Nickel‐Catalyzed Negishi Cross‐Coupling Reactions of Secondary Alkylzinc Halides and Aryl Iodides.

AbstractIn the presence of NiCl2 and terpyridine, a wide range of aromatic iodides are found to undergoes efficient and selective cross‐coupling with secondary alkylzinc halides to afford products of type (III) and (V).

ChemInform Abstract: Integrated Palladium‐Catalyzed Arylation of Heavier Group 14 Hydrides.

AbstractThe integrated palladium‐catalyzed cross‐coupling reaction of aromatic iodides with primary, secondary, or tertiary group 14 hydrides can be applied to the synthesis of a variety of arylated germanes and silanes.

Iodine Monochloride

Iodine monochloride is a chemical compound with the formula ICl. Because of the difference in the electronegativity of iodine and chlorine, ICl is highly polar and behaves as a source of I+. Iodine monochloride is a low melting black or brownish-red solid and widely available (usually in 97-98% purity). It is soluble in alcohol, ether, CS2, acetic acid, acetone and pyridine and hydrolyzes in water to HCl and IOH. ICl explodes on contact with potassium metal, mixes with sodium metal, and it can explode if impacted. Its reaction with PCl3 is extremely exothermic. [¹] Iodine monochloride can be easily prepared by adding an aqueous solution of potassium iodate to potassium iodate dissolved in concentrated HCl, in a closed vessel to avoid the loss of chlorine. [²] Iodine monochloride is a versatile reagent for the synthesis of a large number of organic compounds being employed, for example, as a source of electrophilic iodine in the synthesis of certain aromatic iodides. [³] It cleaves C-Si bonds [4] and can be used in the electrophilic addition to the double bond in alkenes leading to chloroiodoalkanes. [5] When iodine monochloride is reacted with sodium azide in situ, the iodoazide product is obtained. [6] Other examples of synthetic applications of this reagent also include electrophilic substitutions in Csp [²] and electrophilic cyclizations. [7-9]

Integrated Palladium‐Catalyzed Arylation of Heavier Group 14 Hydrides

A convenient procedure has been developed for the preparation of Group 14 compounds by integrated palladium-catalyzed cross-coupling of aromatic iodides with the corresponding Group 14 hydrides in the presence of a base. The reaction conditions can be applied to the cross-coupling of tertiary, secondary, and primary Group 14 compounds. In most cases, the desired arylated products were obtained in synthetically useful yields. Even in the case of aryl iodides containing OH, NH(2), CN, or CO(2)R groups, the reactions proceeded with good to high yields with tolerance of these reactive functional groups. A possible application of this method is the unique synthesis of a fungicidal diarylmethyl(1H-1,2,4-triazol-1-ylmethyl)silane derivative.

ChemInform Abstract: Examination of the Aromatic Amination Catalyzed by Palladium on Charcoal.

AbstractThe Buchwald—Hartwig amination of aromatic iodides, bromides, and chlorides is carried out in the presence of a charcoral‐supported palladium catalyst.

ChemInform Abstract: Free-Radical Carbonylation. Conversion of Aromatic Halides to Aldehydes.

Abstract The free-radical carbonylation of aromatic iodides 1 with carbon monoxide to aromatic aldehydes 2 was successfully achieved under highly diluted conditions ([Bu3SnH]=ca. 0.02M).