Current Organic Chemistry - Volume 15, Issue 11, 2011

Covalent pseudohalides (Scheme 1) are versatile tools in various chemical transformations and are widely used in various fields of chemistry as building blocks for synthesizing polymers, precursors, biologically active materials, and natural products. They occur in nature and smaller derivatives have been detected in the interstellar medium. Pseudohalides have a rich chemistry with a long and fascinating history, which goes back, for some derivatives, for centuries. Not only the chemistry and structure, but the stability of pseudohalides is very varied; there are stable molecules, what are easy to handle, and also reactive and short-lived species whose applications require special means. The present thematic issue includes six reviews, mainly focusing on the synthesis and chemical applications of covalent pseudohalides. Structural properties and spectroscopy are also briefly discussed. The first review of the issue discusses the chemistry of covalent cyanates, including their stability, synthesis, structure, spectroscopy, and chemical applications. Experimentally known derivatives are presented, namely the parent acid and its alkyl, aryl, silyl, SF5, and SeF5 derivatives. Covalent fulminates are regarded as unstable species and their chemistry is largely unexplored yet. This review also presents the available information on the chemistry of organic fulminates. In the second review, the chemistry of organic selenocyanates is summarized, focusing on their synthesis, spectroscopic characterization, and uses in preparative chemistry and biology. The synthesis of inorganic precursors is also discussed, as well as the application of organic selenocyanates in cancer therapy. Small covalent nitrile oxides are important transient species in organic synthesis and widely used for dipolar cycloaddition reactions. The third review focuses on the generation, spectroscopy, structural properties, and synthetic application of small nitrile oxides, XCNO, where the X substituent group is smaller than five atoms, viz. X = hydrogen, halogen, pseudohalogen, alkyl, vinyl, ethynyl, or nitro. The chemistry of nitrile sulfides is presented in the fourth review. The review presents a full coverage of stability, synthesis, spectroscopy, structure, and chemical applications of these unstable species. Nitrile selenides, analogously to nitrile sulfides, have the potential to become important dipolarophiles in preparative chemistry, however, their chemistry is largely unexplored yet. This review also summarizes the present knowledge about nitrile selenides. Hetero-substituted isocyanates and isothiocyanates RX-NCY (X = R2N, RO, or RS; Y = O or S) and the isomeric cyanates RX-OCN, thiocyanates RX-SCN, nitrile oxides RX-CNO, and nitrile sulfides RX-CNS are highly reactive compounds, often transient at room temperature. The chemistry of these compounds, including their generation, identification, spectroscopy, structure, and rearrangement reactions, is reviewed in the fifth contribution. The chemistry of silicon and germanium azides is presented in the sixth review. This review article mainly focuses on the synthesis and synthetic applications of mono-, di-, tri-, and tetraazidosilanes and germanes, as well as their coordination complexes. The spectroscopy and structural properties of silicon and germanium azides are also briefly discussed.

This review is devoted to organic selenocyanates. In the first part, the preparation of these compounds is reported. Organic selenocyanates have been synthesized by reaction of substrates with potassium selenocyanate, selenium diselenocyanate, diselenocyanate or selenium dicyanate. The reactions of selenenyl halides with cyanide ions or selenolates with cyanogen bromide are also efficient. In the second part, the physicochemical properties of organic selenocyanates are described. Infrared, NMR, Photoelectron and Microwave spectra are successively commented for the simplest alkyl, aryl and functionalized derivatives, viz. methyl-, phenyl-, vinyl-, ethynyl-, allyl-, propargyl-, allenyl and cyclopropylselenocyanates. The chemical reactions involving organic selenocyanates are then reported showing the diversity of applications of these compounds in the preparation of other selenium derivatives. In the last part, the recent applications of some derivatives for their antistress, antiradiation, antioxidative, antimutagenic, anticarcinogen and chemopreventive properties are summarized.

Covalent cyanates are important species in preparative chemistry and widely used as synthetic reagents and building blocks for polymers. Covalent fulminates are hardly studied so far. This review focuses on the synthesis, spectroscopy, structural properties, and synthetic applications of cyanates, X-O-C≡ N, and fulminates, X-O-N+≡ C-, where the X substituent group is covalently linked to the oxygen atom.

Silicon and germanium azides are versatile tools in organic synthesis and widely used for various organic transformations e.g. as nucleophiles, 1,3-dipolarophiles, and azide-group transfer agents. This review article focuses on synthesis, spectroscopy, structural properties, and synthetic applications of silicon and germanium azides.

Small covalent nitrile oxides are important transient species in organic synthesis and widely used especially for dipolar cycloaddition reactions. Due to their instability, their isolation and characterization are challenging. This review focuses on the generation, spectroscopy, structural properties, and synthetic application of small nitrile oxides, XCNO, where the X substituent group is smaller than five atoms, viz. X= hydrogen, halogen, pseudohalogen, alkyl, vinyl, ethynyl, or nitro.

Nitrile sulfides, X-C≡N→S, are important transient species in organic synthesis and widely used for dipolar cycloaddition reactions. Nitrile selenides have the potential to become important dipolarophiles in preparative chemistry, however, their chemistry is largely unexplored. This review article focuses on generation, spectroscopic identification, structure, and synthetic applications of nitrile sulfides and nitrile selenides.

Hetero-substituted isocyanates and isothiocyanates RX-NCY (X = R2N, RO, or RS; Y = O or S) and the isomeric cyanates RX-OCN, thiocyanates RX-SCN, nitrile oxides RX-CNO, and nitrile sulfides RX-CNS are highly reactive compounds, often transient at room temperature. The chemistry of these compounds is reviewed. A number of rearrangement reactions is described, particularly [3,3]- sigmatropic shifts, e.g. PhX-NCY → o-HX-C6H4-YCN (X = NR, O, S; Y = O, S); and retro-ene type reactions, RCH2X-NCY → RCH=X + HYCN (X = NR, O, S; Y = O, S). In addition, potential 1,4-shifts of substituent groups of the type R-Y-CNX → R-X-N=C=Y; 1,3- shifts R-C(=Y)-N=X → R-X-N=C=Y; and 1,2-shifts R-C(=Y)-N=X → R-Y-CNX were identified computationally.

Nitrogen heterocycles are widespread in nature and their applications in bioactive pharmaceuticals, agrochemicals and functional materials are well known. A number of protocols have been developed for their syntheses. This review article covers an updated (published during 2005-2008) summary of transition metal-catalyzed approaches for the syntheses of five- and six-membered ring heterocycles with one nitrogen atom via carbon-nitrogen bond forming reactions. The syntheses of five-membered ring heterocycles include pyrroles, pyrrolidines, indoles, oxindoles, isoindoles, indolizines and carbazoles. The syntheses of six-membered nitrogen heterocycles covered are pyridines, piperidines, quinolines and isoquinolines. In some cases, mechanistic rationalizations for the formation of the heterocycles have also been discussed.

The usual synthesis of phosphinates involving the reaction of phosphinic chlorides with alcohols or phenols in the presence of a tertiary amine in an apolar solvent cannot be regarded as “green” and requires expensive P-reagents. We have found that in certain cases phosphinic acids can be esterified by simple alcohols under microwave (MW) conditions. Hence, cyclic phosphinic acids, such as 1-hydroxy-3- and 2-phospholene 1-oxide derivatives (A), 1-hydroxyphospholane 1-oxides (B) and 1-hydroxy-1,2,3,4,5,6- hexahydrophosphinine 1-oxide (C) could be converted to the corresponding esters by reaction with alcohols. Using a 15-fold excess of the alcohol at around 200 ° C, the preparative yields of the phosphinates amounted to 45-60%. The novel reaction is the consequence of the beneficial specific MW effect that was proved by comparative thermal experiments. Phosphinates may also be prepared by the alkylating esterification of phosphinic acids with alkyl halides. Under solventless and MW conditions in the presence of a phase transfer (PT) catalyst and K2CO3, cyclic phosphinic acids A, B and C mentioned above were converted to the corresponding phosphinates in 85-95% yields. It was found that the simultaneous use of the MW and PT catalytic techniques is beneficial when alkyl halides of normal or decreased reactivity are applied. Both methods described can be regarded as environmentally friendly and offer advantages over the traditional esterifications of phosphinic acids.

The reaction of 3,4-dihydro-β-carboline derivatives with 1,3-dipoles, such as a nitrile imine and a nitrile oxide led to triazolopyridoindole and oxadiazolo-pyridoindole derivatives, respectively, that are novel synthetic alkaloids. Stereostructure, stability and further reactions of the pyridoindoles were also investigated. The oxadiazolo-pyridoindoles underwent reaction with a second unit of nitrile oxide to afford the corresponding trisubstituted 1,2,4-triazole 2-oxides. The mechanisms of the above reactions were studied in detail by high level quantum chemical calculations. It was found that the reaction of the 1,3-dipoles is not an expected 1,3-cycloaddition, but rather a stepwise addition reaction. The exact mechanism was found to be dependent on the substitution pattern.

This account is focused on highlighting the recent advances on synthetically-useful organic reactions employing siliconcentered radicals in water, and presenting new reactions in water, mediated by silyl radicals. In doing so, several types of organic radical transformations will be discussed, such as reduction of organic halides utilizing non toxic organosilane reducing agents in water, transformation of azides into amines, synthesis of protecting silyl ethers in water, hydrosilylation reactions of carbon-carbon double and triple bonds, and radical cyclization reactions in water induced by silicon-centered radicals. More recently, intermolecular radical carboncarbon bond formation reactions mediated by silyl radicals have allowed the synthesis of perfluoroalkyl-substituted compounds in water, widening the scope for the syntheses of fluorophoes. These silicon radical-mediated chain reactions in water are initiated through different methods, among which, thermal, photochemical, and dioxygen initiations are reported to be the most successful methods in water. A versatile aspect of the radical methodology employed in water will be presented in terms of dealing with water-soluble and organic solvent- soluble substrates in these silicon radical-mediated reactions in water. In this regard, for an efficient chain process to take place in water, a chain carrier must be used when water-soluble substrates are employed, whereas organic solvent-soluble materials do not require a chain transporter when silyl radicals are used in water.

With the development of separation materials, more and more complex natural products with poly-stereogenic centers are obtained. However, due to small quantity of the isolated compounds, or no crystal formed, or complex 2D NMR correlation signals, absolute configuration identification for these compounds becomes difficult. Now, computational methods provide researchers many benefits in structural determinations for chiral natural products. Computational methods include (1) optical rotation (OR) and its dispersion (ORD) computations; (2) electronic circular dichroism (ECD or CD) calculations; (3) computations of determinant of matrix for stereogenic centers. In methods (1) to (2), the mostly used quantum theory contained density functional theory (DFT) with different basis sets, e.g. B3LYP/aug-cc-pVDZ//B3LYP/6-31G(d). Effects from solvents on OR value can be investigated using different corresponding software. In the cases, optimizations performed in the corresponding solution are helpful to obtain the correct predictions although it is not usual at present time. Matrix model as one of the mathematic methods is different from quantum methods, which is of easily being understood and effective in absolute configuration assignment for acyclic chiral compounds. In this review, necessary theory basis for the three methods are simply introduced for modern readers, the focus of which is the application of these methods in natural product chemistry by various examples reported in different journals from 1998 to the end of April of 2010 except for matrix method to the May of 2010 based on an experimental chemist's viewpoints.

Molecular imprinted polymers (MIPs) are being developed as a powerful way to achieve molecular recognition via the template- directed synthesis which results in the formation of specific cavities complementary to the molecule in shape and chemical functionality. One of the most successful application areas of MIPs is chromatographic sorbents. The use of MIPs sorbents in capillary electrochromatography (CEC) is attractive in that it combines predetermined selectivity, higher efficiency and shorter analysis time. CECbased MIPs consume fewer templates or monomers for the molecular imprinting, which is desired for the need of green chemistry. The small dimensions of capillary demand the development of novel polymer formats which allow the application to miniaturized system. The review gives a full overview of CEC-based MIPs including the various formats, current trends in this field and application in the separation of organic compounds.