Predictions of substituent effects in thermal azide 1,3-dipolar cycloadditions: implications for dynamic combinatorial (reversible) and click (irreversible) chemistry

Substituent effects in 1,3-dipolar cycloadditions of azides with alkenes and alkynes were investigated with the high-accuracy CBS-QB3 method. The possibilities for noncatalytic activation and the reversibility or irreversibility of these reactions was explored; the possibilities for uses in dynamic combinatorial chemistry (DCC) or click chemistry were explored. The activation enthalpies for reactions of ethylene and acetylene with hydrazoic acid, formyl, phenyl-, methyl-, and methanesulfonylazides exhibit modest variation, with Delta H++ ranging from 17 to 20 kcal/mol. A detailed study of formylazide cycloadditions with various alkenes and alkynes reveals a narrow range of activation enthalpies (17-21 kcal/mol). The activation enthalpies for the reactions of azides with alkenes and alkynes are similar. FMO theory and distortion/interaction energy control have been used to rationalize the rates and regiochemistries of cycloadditions involving alkene dipolarophiles. Significantly, triazoles, formed from alkynes, are 30-40 kcal/mol more stable than tetrazolines formed from alkenes. On the basis of initial reactant concentrations, kinetic and thermodynamic values are suggested for the identification of reversible reactions that approach equilibrium over 24 h, as well as for fast irreversible reactions. Although azide cycloadditions are suitable for irreversible chemistry and are typically unsuitable for reversible applications, theoretical procedures established by these studies have provided guidelines for the prediction of useful reversible libraries.     

Synthesis of Pyrrolidine Derivatives by a Platinum/Brønsted Acid Relay Catalytic Cascade Reaction

A new catalytic reaction for the synthesis of pyrrolidine derivatives is presented. The method implies the coupling of N‐Boc‐protected alkynamine derivatives and appropriate alkenes or alkynes in a process catalysed by a platinum/triflic acid catalytic binary system. This reaction is believed to proceed through a cascade process implying an initial platinum‐catalysed cycloisomerization of the alkynamine derivative followed by a triflic acid promoted nucleophilic addition of the alkene or alkyne and trapping of the cationic species formed by the Boc group. Not only simple alkenes and alkynes were used in this reaction but also allyltrimethylsilane and propargyltrimethylsilane. Particularly, when allyltrimethylsilane is used as the alkene counterpart interesting bicyclic compounds containing a trimethylsilane group are obtained. However, when propargyltrimethylsilane is used in the presence of water we observed the formation of a related bicyclic compound lacking the trimethylsilane group and containing an exocyclic carbon?carbon bond.     

Phospha-organic chemistry: panorama and perspectives

Since the beginning of the seventies, organophosphorus chemistry has been completely rejuvenated by the discovery of stable derivatives in which phosphorus has the coordination numbers one or two. The chemistry of these compounds mimics the chemistry of their all-carbon analogues. In this Review article this analogy is discussed for the phosphorus counterparts of alkenes, alkynes, and carbenes. In each case, the synthesis, reactivity, and coordination modes are briefly examined. Some special electronic configurations are also discussed, which include one-electron Pbond;P bonds, strained bonds, and aromatic systems. To conclude, some potential applications of this chemistry in the areas of molecular materials and homogeneous catalysis are presented.     

Electrospray ionization mass spectrometric characterization of key Te(IV) cationic intermediates for the addition of TeCl4 to alkynes

Tellurium tetrachloride adds to alkynes via two pathways: a concerted syn-addition that yields Z-tri- and -tetrasubstituted alkenes or an anti-addition that yields E-alkenes. The mechanistic aspects of these divergent pathways for TeCl4 addition to alkynes have been investigated by on-line electrospray ionization (tandem) mass spectrometry (ESI-MS(/MS)). Via ESI-MS(/MS), we have been able to intercept and characterize the active electrophile TeCl3+ in tetrahydrofuran (THF) solutions of TeCl4, as well as its THF complex and several TeClx(OH)y+ derivatives. For the first time, also, key Te(IV) cationic intermediates of the electrophilic addition of TeCl4 to alkynes were captured for gas-phase MS investigation. The detailed structural data of cyclic tellurane intermediates intercepted herein seems to provide insights into the coordinative behavior of the Te(IV) atom and its mode of action towards biological targets.     

Reductive dehalogenation of aliphatic vic-dihalides with metallic samarium in a methanolic medium

In the title reaction, eight vic-dibromides and three vinylene dibromides gave the corresponding debromination products (alkenes and alkynes) at room temperature under neutral condition and an argon atmosphere. 2,3-Dibromosuccinic acid derivatives gave overreduction products or an unusual coupling dimer.     

Radical-mediated vicinal addition of alkoxysulfonyl/fluorosulfonyl and trifluoromethyl groups to aryl alkyl alkynes

The addition of sulfonyl radicals to alkenes and alkynes is a valuable method for constructing useful highly functionalized sulfonyl compounds. The underexplored alkoxy- and fluorosulfonyl radicals are easily accessed by CF₃ radical addition to readily available allylsulfonic acid derivatives and then β-fragmentation. These substituted sulfonyl radicals add to aryl alkyl alkynes to give vinyl radicals that are trapped by trifluoromethyl transfer to provide tetra-substituted alkenes bearing the privileged alkoxy- or fluorosulfonyl group on one carbon and a trifluoromethyl group on the other. This process exhibits broad functional group compatibility and allows for the late-stage functionalization of drug molecules, demonstrating its potential in drug discovery and chemical biology.

An unprecedented method for vicinal addition of alkoxysulfonyl/fluorosulfonyl and trifluoromethyl groups to aryl alkyl alkynes has been developed to afford useful alkenylsulfonate esters and alkenylsulfonyl fluorides.     

Catalytic synthesis of oligoene and enyne derivatives through carbometalation of internal alkynes

A number of new synthetic methods for π‐conjugated oligoene and enyne compounds are described. Thus, diene and higher oligoene derivatives are selectively constructed by palladium‐catalyzed arylation reactions of internal alkynes in the presence of arylboronic acids or alkenes as terminators. In contrast, the synthesis of various enyne derivatives is achieved effectively by homo‐ or cross dimerization of alkynes under rhodium catalysis. © 2008 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 8: 326–336; 2008: Published online in Wiley InterScience ( www.interscience.wiley.com ) DOI 10.1002/tcr.20158     

Migratory Hydrogenation of Terminal Alkynes by Base/Cobalt Relay Catalysis

Migratory functionalization of alkenes has emerged as a powerful strategy to achieve functionalization at a distal position to the original reactive site on a hydrocarbon chain. However, an analogous protocol for alkyne substrates is yet to be developed. Herein, a base and cobalt relay catalytic process for the selective synthesis of (Z)‐2‐alkenes and conjugated E alkenes by migratory hydrogenation of terminal alkynes is disclosed. Mechanistic studies support a relay catalytic process involving a sequential base‐catalyzed isomerization of terminal alkynes and cobalt‐catalyzed hydrogenation of either 2‐alkynes or conjugated diene intermediates. Notably, this practical non‐noble metal catalytic system enables efficient control of the chemo‐, regio‐, and stereoselectivity of this transformation.     

Advances in chemoselective and/or stereoselective semihydrogenation of alkynes

The chemoselective semihydrogenation of alkynes is one of the most important reactions in synthetic organic chemistry. During the last decade or so, a multitude of innovative catalytic methods have been developed to address the selective hydrogenation of alkynes. This digest focuses on the recent developments in chemoselective semihydrogenation of alkynes to alkenes.     

Rh-catalyzed addition of boronic acids to alkynes for the synthesis of trisubstituted alkenes in a biphasic system - Mechanistic study and recycling of the Rh/m-TPPTC catalyst

The versatile preparation of trisubstituted alkenes via selective Rh-catalyzed arylation of alkynes is described in water and in a water/toluene biphasic system. For hydrophobic alkyl alkynes, the reaction afforded either alkenes or dienes depending on the temperature and the solvent conditions. Aryl, heteroaryl, silylated and alkyl substituted alkynes reacted equally well with various boronic acids, leading regioselectively to functionalized alkenyl derivatives in high yields (65-99%). The mechanism was investigated in toluene/water mixture or water and involves a vinylrhodium complex. The efficient recycling of the Rh/m-TPPTC system is disclosed with excellent yield (92-96%) and purity of the alkene.     

Novel phosphoryl derivatization method for peptide sequencing by electrospray ionization mass spectrometry

A one-step phosphoryl derivatization method has been used in a peptide sequencing procedure for electrospray ionization tandem mass spectrometry (ESI-MS/MS). The sodiated derivatized peptides exhibit very simple dissociation patterns, in which two kinds of fragment ions, [b(n) + OH + Na]+ and [a(n) + Na]+, are formed. Since the amino acid residues are lost sequentially from the C-terminus, peptide sequences can be identified easily. The fragmentation efficiency of peptides increased as a result of the phosphorylation, and also provided peaks of useful intensity at lower m/z. A peptide with lysine at the C-terminus was derivatized and analyzed by ESI-MS/MS. Similar mass spectra, from which the sequence could be read out, were obtained. This is a novel derivatization method yielding neutral derivatives that should be suitable for peptide sequencing by LC/ESI-MS/MS.     

Detection and identification of quinonemethide triterpenes in Peritassa campestris by mass spectrometry

Analysis of tingenone and tingenol quinonemethide triterpenes was made by gas chromatography/mass spectrometry (GC/MS) of their trimethylsilyl (TMS) ethers. An extra TMS group, in addition to those predicted from the known structures, is added to these compounds during the derivatization process. The electron impact mass spectra showed base peaks at m/z 549 and 623, respectively, for the TMS derivatives of tingenone and tingenol, and electrospray (ES) and collision-activated dissociation (CAD) studies indicate that these ions correspond to losses of a methyl group from the derivatives studied. A mechanism, based on ES-MS/MS studies, is suggested for the derivatization and fragmentation pattern.     

An environmentally benign synthesis of isoxazolines and isoxazoles mediated by potassium chloride in water

An effective and environmentally benign procedure for the synthesis of isoxazolines and isoxazoles has been developed by a cycloaddition of nitrile oxides with alkenes or alkynes in water. In this approach, potassium chloride is first oxidized into chlorine in water by the environmentally friendly oxidant Oxone®, then aldoximes are oxidized into nitrile oxides by the in situ generated hypochlorous acid, finally a 1,3-dipolar cycloaddition between nitrile oxides and alkenes or alkynes occurs to provide the corresponding isoxazolines and isoxazoles in good yields.     

Alkynyl- and Alkenyl(phenyl)iodonium Compounds. New Synthetic Methods (86)

Compounds with highly coordinated, polyvalent main-group elements represent an interesting alternative to the many well-known transition-metal complexes. Among the oldest and best known stable examples of such organic molecules are the iodine(III) compounds. Diaryliodonium species, Ar₂IX, for example, have been known for over a hundred years and play an important role in lithography. Likewise, acetylenes and olefins are among the oldest, most important, and most valuable compounds in chemistry. Besides simple hydrocarbon alkenes and alkynes, numerous functionalized derivatives are also known and widely employed in organic chemistry. Despite the ubiquity and prominance of both I^III species and olefins and acetylenes, the combination of these two types of functional groups in a single molecular unit, namely compounds with polyvalent iodine and at least one alkyne or olefin residue, was unknown until recently. The successful preparations of simple alkynyl- and alkenyl-(phenyl)iodonium species during the 1980s has resulted in a renaissance in both acetylene and I^III chemistry. These alkynyliodonium compounds readily undergo nucleophilic substitution on the alkyne moiety (S_N-A reactions) which are difficult with other substrates. The application of a wide variety of nucleophiles in this reaction resulted in diverse functionalized alkynes including previously unknown acetylenic carboxylates, sulfonates, and phosphates. These are excellent substrates for cycloaddition reactions as well as numerous other interesting chemical transformations.     

Metal-catalyzed reactions of diborons for synthesis of organoboron compounds

Metal-catalyzed borylation of alkenes, alkynes, arenes, and organic halides with B-B or H-B compounds has been developed for the synthesis of organoboron compounds from simple organic substrates. The platinum(0)-catalyzed addition of bis(pinacolato)diboron to alkenes and alkynes provided a method for the stereoselective synthesis of cis-bis(boryl)alkanes or cis-bis(boryl)alkenes. The addition of diboron to 1,3-dienes with platinum(0) complexes provided a new access to cis-1,4-bis(boryl)-2-butene derivatives, which are versatile reagents for diastereoselective allylboration of carbonyl compounds. The first one-step procedure for the syntheses of aryl-, vinyl-, and allylboronates was achieved via crosscoupling reactions of diborons with aryl and 1-alkenyl halides or triflates and allyl acetates. Direct C-H borylation of arenes catalyzed by a transition metal complex was studied as an economical protocol for the synthesis of a variety of arylboron derivatives. Ir-catalyzed C-H borylation of arenes, heteroarenes, and benzylic positions of alkylarenes by bis(pinacolato)diboron or pinacolborane furnished aryl-, heteroaryl-, and benzylboron compounds. This article discusses the mechanisms of these reactions and their synthetic applications.     

Controlled Trifluoromethylation Reactions of Alkynes through Visible‐Light Photoredox Catalysis

The control of a reaction that can form multiple products is a highly attractive and challenging concept in synthetic chemistry. A set of valuable CF₃‐containing molecules, namely trifluoromethylated alkenyl iodides, alkenes, and alkynes, were selectively generated from alkynes and CF₃I by environmentally benign and efficient visible‐light photoredox catalysis. Subtle differences in the combination of catalyst, base, and solvent enabled the control of reactivity and selectivity for the reaction between an alkyne and CF₃I.     

Cu(I)-catalyzed intramolecular cyclization of alkynoic acids in aqueous media: a "click side reaction"

Alkynoic acids, in particular, 4-pentynoic acid derivatives, undergo intramolecular cyclizations to enol lactones under reaction conditions typically applied for the Cu(I)-catalyzed cycloaddition of terminal alkynes and azides (click chemistry). Starting from appropriate alkynoic acid derivatives, either enol lactones or 1,2,3-triazole click products can be obtained selectively by Cu(I) catalysis in aqueous media.     

Metal cluster catalysis: III. Selective homogeneous hydrogenations catalyzed by [n5-C5H5)Fe(u3-CO)l4

The iron cluster, [(n⁵-C₅H₅)Fe(μ₃-CO)]₄, 1, catalyzes the selective hydrogenation of alkynes to alkenes at 100–130° and 100–1000 psig and the selective reduction of terminal alkynes to olefins in the presence of alkenes or internal alkynes. Internal alkynes are slowly reduced to $\text{cis}$ olefins, aryl nitro groups to aniline derivatives, and terminal activated carbon-carbon double bonds (methyl acrylate, acrylonitrile) are hydrogenated. The cluster concentration, monitored by high pressure liquid chromatography, was unchanged after 1148 and 1410 turnovers. Cluster 1 was isolated in 95–97% yields after catalytic reduction (1000 turnovers) and no other iron-containing species were detected. After 280 turnovers, the catalyst solution was filtered through an ultrafiltration membrane into a second vessel where hydrogenation of 1-pentyne continued. Fragmentation of 1 tc     

Derivatization in mass spectrometry-3. Alkylation (arylation)

The review is devoted to alkylation (arylation) as a widely employed derivatization procedure for the protection of OH (carboxylic acids, phosphoric acids, sulfonic acids, alcohols, polyols, phenols, enols), SH (thiols) and NH (amines, amides) groups in order to increase volatility, to improve the chromatographic properties and, if possible, mass spectral properties of derivatives. Chemical aspects of derivatization and various alkylation (arylation) reagents and reaction procedures are described. Specific mass spectral (electron ionization, chemical ionization) features of derivatives helpful in identification, structure elucidation, profiling and quantitative determination of the above-mentioned polar compounds by coupled gas chromatography or high-performance liquid chromatography are discussed. Some common analytical applications of the procedures in organic chemistry, clinical chemistry, environmental chemistry etc. are briefly summarized.     

Alternative procedure for charged derivatization to enhance detection responses of steroids in electrospray ionization-MS

A derivatization procedure has been examined to enhance the electrospray ionization (ESI)-MS detectabilities of steroids that charged derivatization is not suitable for. The derivatization procedure with 2-hydrazinopyridine or isonicotinoyl azide was very effective for the sensitive detection of di-oxosteroids or di-hydroxysteroids, respectively, and the detection limits of the resulting derivatives were as low as about 2 fmol. The derivatives also provided intense characteristic product ions in the MS-MS, which are expected to be usable for the selected reaction monitoring mode.