The Total Synthesis of Eleutherobin: A Surprise Ending

An “sp ² –sp ³ Stille coupling” of the vinyl triflate 1 and the stannyl compound 2 is a key step toward the completion of the total synthesis of eleutherobin, a natural product exhibiting taxol-like cytotoxic activity.     

Studies towards the Synthesis of (+)-Dictyoxetane

The dolabellane-type diterpene dictyoxetane represents a significant challenge to synthetic organic chemistry. Methodology directed towards the total synthesis of naturally occurring (+)-dictyoxetane is reported. Catalytic asymmetric synthesis of the trans-hydrindane ring system is achieved through chemoselective deoxygenation of the Hajos-Parrish ketone. An alternative to the Garst-Spencer furan annulation is developed for the synthesis of a 2,5-dimethyl, tetrasubstituted furan, employing a tandem 5-exo-dig alcohol to alkyne cyclisation/aromatisation reaction as a key step. The (4+3) cycloaddition reaction of an oxyallyl cation with a tetrasubstituted furan is established on a cyclohexanone-derived model system, and a range of related (4+3) cycloadditions investigated on a homochiral, trans-hydrindane-fused furan, where regio- and diastereoselectivity is required for the natural product synthesis. In an alternative (4+2) Diels-Alder approach, a C₂-symmetric vinyl sulfoxide-based chiral ketene equivalent is used to prepare oxanorbornenes with the same oxygen bridge stereochemistry found in the 2,7-dioxatricyclo[4.2.1.0^3,8]nonane ring system of the natural product.     

Conversion of 1,3- into 1,4-dicarbonyl compounds by means of α-phosphoryl sulphides. Total synthesis of dihydrojasmone and methylenomycin B.

An effective synthesis of 1,4-dicarbonyl systems involving the Horner—Wittig reaction of α-phosphoryl sulphides with the half-protected 1,3-dicarbonyl compounds followed by hydrolysis of the vinyl sulphides formed is described. The total synthesis of dihydrojasmone and methylenomycin B employing this approach is reported.     

Synthesis of vinyl 1,2-diketones

A new route is outlined for preparation of vinyl 1,2-diketones via a three-step sequence. First, allylic alcohols are photooxidized by ¹O₂ to hydroperoxides, which are reduced to vinyl 1,2-diols. These vinyl 1,2-diols are oxidized to vinyl 1,2-diketones with oxoammonium salts, which are prepared in situ from organic nitroxyl radicals. The new route is short, avoids the use of protecting groups, and is generally applicable to obtain aliphatic or aromatic vinyl 1,2-diketones.     

A General Synthesis of 2-Methoxy-2-Cyclohexenones

The preparation of octalinone 1 at an early stage of a recent synthesis of valeranone¹ required the use of a Robinson annelation with 1,4-dimethoxy-2-butanone (2a), a methoxymethyl vinyl ketone (3) equivalent. The following syntheses of 2-methoxy-2-cyclohexenones illustrate further examples of the heretofore unexploited reaction.²     

Sequence-regulated oligomers and polymers by living cationic polymerization. III. Synthesis and reactions of sequence-regulated oligomers with a polymerizable group

New sequence-regulated macromonomers ( 3 ) with a vinyl ether terminal were prepared by the HI/ZnI₂-mediated living cationic polymerization of vinyl ethers: CH₃? CH(OR¹)? CH₂CH(OR²)? C(COOEt)₂CH₂CH₂OCH?CH₂ ( 3a : R¹ = nBu, R² = CH₂CH₂OCOPh; 3b : R¹ = iOct, R² = CH₂CH₂Cl). The synthesis consisted of three consecutive steps: (i) quantitative addition of hydrogen iodide to the first vinyl ether into an adduct [CH₃? CH(OR¹)? l]; (ii) propagation of a second vinyl ether from the adduct in the presence of zinc iodide; and (iii) quenching the resulting AB-type heterodimeric living intermediate with a carbanion [^θC(COOEt)₂CH₂CH₂OCH?CH₂] carrying a vinyl ether group. The HI/ZnI₂-initiated living cationic polymerization of 3a and 3b yielded narrowly distributed polymers $\left( {\overline {DP}} _{_n } \sim 10 \right)$ consisting of a poly(vinyl ether) backbone and sequence-regulated oligomer branches. The terminal vinyl ether function of 3 was also utilized to prepare pentamers and hexamers with controlled sequence of functional vinyl ethers by selective dimerization and chain extension reactions with HI/ZnI₂. © 1993 John Wiley & Sons, Inc.     

Synthesis of [2-(vinyloxy)ethyl]uracil and [2-(allyloxy)ethyl]uracil

A synthesis is reported for N¹-mono- and N¹,N³-disubstituted uracil derivatives containing a terminal carbon-carbon double bond in the side-chain. Alkylation of vinyl 2-chloroethyl ether by uracil potassium salts leads to a mixture of 1-[2-(vinyloxy)ethyl] and 1,3-di[2-(vinyloxy)ethyl] derivatives while treatment of 2,4-bis(trimethylsilyloxy)pyrimidines by vinyl 2-chloroethyl ether leads exclusively to N¹-monosubstituted products. Alkylation of cytosine by this chloroether gave 1-[2-(vinyloxy)ethyl]cytosine. The synthesis of 1-[2-(allyloxy)ethyl]uracil derivatives was carried out by treatment of uracil potassium salts by 1-(allyloxy)-2-(p-toluenesulfonyloxy)ethane.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 393–397, March, 1993.     

Synthesis of ferrocene boronic acid-based block copolymers via RAFT polymerization and their micellization,redox responsive and glucose sensing properties

Current study is focused on the synthesis of three novel diblock copolymers poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-polymethyl vinyl amido phenyl boronic acid, poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-poly vinylamido phenyl boronic acid and poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-polystyrene boronic acid using S-methoxycarbonylphenylmethyl dithiobenzoate as reversible addition–fragmentation chain transfer polymerization agent. The synthesized block copolymers were characterized by gel permeation chromatography, fourier transform infrared spectroscopy, ¹H nuclear magnetic resonance spectroscopy, dynamic light scattering, scanning electron microscopy and transmission electron microscopy. Detailed micellization behaviour of poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-polymethyl vinyl amido phenyl boronic acid (in binary organic solvents mixture and aqueous solution) was studied. Comparative studies of micellization showed that the larger aggregates were obtained in binary organic solvents system than during dialysis in aqueous medium. The redox responsive behaviour of poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-polymethyl vinyl amido phenyl boronic acid was investigated by water soluble oxidizing (Ammonium cerium nitrate) and reducing (Sodium hydrogen sulphite) agents. Glucose binding/sensing properties of poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-polymethyl vinyl amido phenyl boronic acid were also explored by micellization. It was found that the increase in polarity and swelling of poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-polymethyl vinyl amidophenyl boronic acid micelles was due to the redox behaviour of ferrocene, while binding of glucose with boronic acids hydroxyls appears as unimers or small aggregates.     

Synthesis of monomers containing guanine or guanine precursors as substituent groups

The synthesis of four new monomers containing guanine or a guanine precursor was achieved. These were two isomeric acid ester derivatives of guanine and two isomeric vinyl ether derivatives of N²-acetylguanine. In the case of the synthesis of the guanine acid esters IV and V, it was necessary to prepare first the guanine alcohol derivatives II and III. These N-7 and N-9 isomeric alcohols of guanine were separated by fractional crystallization. Subsequent esterification of these alcohols with maleic anhydride gave the desired products. In the other case, N²-acetylguanine was alkylated with 2-chloroethyl vinyl ether to yield the N-7 and N-9 isomer VI and VII, respectively. These were separated using flash column chromatography.     

Synthesis of thermotropic liquid crystalline all-Trans-p-Phenylenevinylene oligomers via two-step metathesis

Liquid crystalline products of oligomeric p-phenylenevinylene derivates were prepared metathetically using a stable molybdenum carbene complex (Mo(NAr^Me₂)(CHCMe₂Ph)[OCMe(CF₃)₂]₂). The synthesis was conducted via two steps: 1. Metathesis polycondensation of 2, 5-dialkyl-1, 4-divinylbenzenes to oligo-(2, 5-dialkyl-1, 4-phenylenevinylene)s, 2. Endcapping of the vinyl groups via cross-metathesis using 3-hexene. The products were characterized by¹H-NMR and UV/Vis spectroscopy, as well as by DSC.     

Microwave Irradiation: Alternative Heating Process for the Synthesis of Biologically Applicable Chromones,Quinolones, and Their Precursors

Microwave irradiation has become a popular heating technique in organic synthesis, mainly due to its short reaction times, solventless reactions, and, sometimes, higher yields. Additionally, microwave irradiation lowers energy consumption and, consequently, is ideal for optimization processes. Moreover, there is evidence that microwave irradiation can improve the regioselectivity and stereoselectivity aspects of vital importance in synthesizing bioactive compounds. These crucial features of microwave irradiation contribute to its inclusion in green chemistry procedures. Since 2003, the use of microwave-assisted organic synthesis has become common in our laboratory, making our group one of the first Portuguese research groups to implement this heating source in organic synthesis. Our achievements in the transformation of heterocyclic compounds, such as (E/Z)-3-styryl-4H-chromen-4-ones, (E)-3-(2-hydroxyphenyl)-4-styryl-1H-pyrazole, (E)-2-(4-arylbut-1-en-3-yn-1-yl)-4H-chromen-4-ones, or (E)-2-[2-(5-aryl-2-methyl-2H-1,2,3-triazol-4-yl)vinyl]-4H-chromen-4-ones, will be discussed in this review, highlighting the benefits of microwave irradiation use in organic synthesis.     

Synthesis of 13C and 2H Labeled Vinyl Pyruvate and Hyperpolarization of Pyruvate

The hyperpolarization of nuclear spins has enabled unique applications in chemistry, biophysics, and particularly metabolic imaging. Parahydrogen-induced polarization (PHIP) offers a fast and cost-efficient way of hyperpolarization. Nevertheless, PHIP lags behind dynamic nuclear polarization (DNP), which is already being evaluated in clinical studies. This shortcoming is mainly due to problems in the synthesis of the corresponding PHIP precursor molecules. The most widely used DNP tracer in clinical studies, particularly for the detection of prostate cancer, is 1-¹³C-pyruvate. The ideal derivative for PHIP is the deuterated vinyl ester because the spin physics allows for 100 % polarization. Unfortunately, there is no efficient synthesis for vinyl esters of β-ketocarboxylic acids in general and pyruvate in particular. Here, we present an efficient new method for the preparation of vinyl esters, including ¹³C labeled, fully deuterated vinyl pyruvate using a palladium-catalyzed procedure. Using 50 % enriched parahydrogen and mild reaction conditions, a ¹³C polarization of 12 % was readily achieved; 36 % are expected with 100 % pH₂. Higher polarization values can be potentially achieved with optimized reaction conditions.     

晶种协同廉价有机模板导向合成高纯度MCM-49沸石

采用廉价低毒性的环己胺（CHA）作为有机模板剂,并合理添加少量MCM-49沸石晶种,在静态水热条件下成功合成了高纯度MCM-49沸石.研究了起始凝胶组成（如Al₂O₃/SiO₂,H₂O/SiO₂,CHA/SiO₂,晶种/SiO₂,Na₂O/SiO₂）、晶化温度和时间等因素对合成MCM-49沸石的影响.通过XRD、SEM、N₂吸附、固体²⁷Al和²⁹Si MAS NMR等手段表征产物,结果表明合成的MCM-49沸石具有良好的结晶度、均匀的晶体尺寸、高比表面积和纯的四配位Al³⁺物种.热重差热分析（TG-DTA）和固体¹³C MAS NMR表征结果证实CHA是作为模板剂填充在沸石产物的孔道内.这种合成MCM-49的方法具有廉价和低毒性的特点,对其产业应用有潜在的重要价值.     

Synthesis and characterization of new polymeric ionic liquid microgels

A new two‐step route toward the synthesis of polymeric ionic liquid microgel particles is presented. In the first step, hydrophilic microparticles were prepared by the concentrated emulsion polymerization of the ionic liquid 1‐vinyl‐3‐ethylimidazolium bromide in the presence of small amounts of N,N‐dimethylenebisacrylamide as a crosslinking agent. In the second step, the bromide anion was exchanged in water with different anions such as BF, CF₃SO, (CF₃SO₂)₂N^?, (CF₃CF₂SO₂)₂N^?, and dodecylbenzenesulfonate, and this resulted in the coagulation of the microparticles, which were easily recovered by filtration. The obtained polymeric ionic liquid microparticles could be swollen in a very broad range of organic solvents, including apolar organic solvents. As an application, glucose oxidase was encapsulated inside polymeric ionic liquid microparticles, which were used in an amperometric biosensor. The response of the biosensor showed excellent values that strongly depended on the nature of the polymeric ionic liquid counteranion in the order of Br^? > BF > (CF₃SO₂)₂N^?. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 3958–3965, 2006     

Total Synthesis and Stereochemical Revision of Phacelocarpus 2‐Pyrone A

The first total synthesis of phacelocarpus 2‐pyrone A is reported. The original natural compound was tentatively assigned (by NMR spectroscopy) as containing two cis‐alkenes and a trans‐vinyl ether connected to a 2‐pyrone ring motif. Our computational predictions indicated that a cis‐vinyl ether motif was equally feasible. Attempts to prepare the trans‐vinyl ether were met with no success. The all cis‐target compound was synthesised in nine steps, employing key regio‐ and stereoselective reactions including Au^I‐catalysed vinyl etherification, Wittig alkenylation and end‐game Stille macrocyclisation. Analysis of the NMR data enabled identification and confirmation of the correct structure of phacelocarpus 2‐pyrone A, containing a cis‐vinyl ether. Our studies pave the way for future development of methodologies to these structurally distinct pyrone skipped‐polyenyne natural products.     

Convenient Synthesis of Lithium Methyl Selenide An Efficient Reagent for the SN2 Cleavage of Esters

The synthesis of alkyl selenides has attracted considerable attention^1-3 during the last few years in view of their importance as reagents and intermediates in organic synthesis.⁴ Several methods have been described for the introduction of selenium into organic molecules starting from elemental selenium.^1–3     

Facile Synthesis of Gold Icosahedra in an Aqueous Solution by Reacting HAuCl4 with N‐Vinyl Pyrrolidone

Herein we describe a protocol that generates Au icosahedra in high yields by simply mixing aqueous solutions of HAuCl₄ and N‐vinyl pyrrolidone. Our mechanistic study reveals that water plays an important role in this synthesis: as a nucleophile, it attacks the gold–vinyl complex, leading to the production of an alcohol‐based Au^I intermediate. This intermediate then undergoes a redox reaction in which Au^I is reduced to Au⁰, leading to the formation of Au atoms and then Au icosahedra of about 18 nm in size at a yield of 94 %, together with a carboxylic acid in the final product. This new protocol has also been employed to prepare multiply twinned nanoparticles of Ag (15–20 nm in size), spherical aggregates (25–30 nm in size) of Pd nanoparticles, and very small nanoparticles of Pt (2 nm in size). Since no organic solvent, surfactant, or polymer stabilizer is needed for all these syntheses, this protocol may provide a simple, versatile, and environmentally benign route to noble‐metal nanoparticles having various compositions and morphologies.     

Synthesis and Thermolysis of Cycloalkenyl Azides and Iminophosphoranes Aldehydes: A New Pathway to Bisannelated Pyridines

Nucleophilic substitution on vinyl halides usually occurs when these compounds possess an electron withdrawing group at the D position as well as a good leaving group at the Q position Thus D-chlorovinyl ketones are suitable starting materials for the synthesis of D-azidovinyl ketones' Nesmeyanov and Rybuiskaya² found that this substitution proceeds with the retention of configuration regarding the C=C bond Consequently, trans-β-halovinyl ketones yield the corresponding trans-D-azido ketones, but very few cis-D-azidovinyl ketone or aldehyde are described3 These latter Isomers have been reported to be unstable and to decompose spontaneously to isoxazoles² In the case of the cycloalkenyl series β-azidovinyl ketones were only suggested as reaction Intermediates^l,3     

One‐pot synthesis of a new high vinyl content hybrid silica monolith dedicated to nanoliquid chromatography

A new vinyltrimethoxysilane‐based hybrid silica monolith was developed and used as a reversed‐phase capillary column. The synthesis of this rich vinyl hybrid macroporous monolith, by cocondensation of vinyltrimethoxysilane with tetramethoxysilane, was investigated using an unconventional (formamide, nitric acid) porogen/catalyst system. A macroporous hybrid silica monolith with 80% in mass of vinyltrimethoxysilane in the feeding silane solution was obtained and compared to a more conventional low vinyl content hybrid monolith with only of 20% vinyltrimethoxysilane. Monoliths were characterized by scanning electron microscopy, ²⁹Si nuclear magnetic resonance spectroscopy and N₂ adsorption–desorption. About 80% of the vinyl precursor was incorporated in the final materials, leading to 15.9 and 61.5% of Si atoms bonded to vinyl groups for 20% vinyltrimethoxysilane and 80% vinyltrimethoxysilane, respectively. The 80% vinyltrimethoxysilane monolith presents a lower surface area than 20% vinyltrimethoxysilane (159 versus 551 m²/g), which is nevertheless compensated by a higher vinyl surface density. Chromatographic properties were evaluated in reversed‐phase mode. Plots of ln(k) versus percentage of organic modifier were used to assess the reversed‐phase mechanism. Its high content of organic groups leads to high retention properties. Column efficiencies of 170 000 plates/m were measured for this 80% vinyltrimethoxysilane hybrid silica monolith. Long capillary monolithic columns (90 cm) were successfully synthesized (N = 120 000).     

Studies on a Vinyl Ruthenium‐Modified Squaraine Dye: Multiple Visible/Near‐Infrared Absorbance Switching through Dye‐ and Substituent‐Based Redox Processes

The bis(vinyl ruthenium)‐modified squaraine dye 1 was synthesized by treatment of [RuHCl(CO)(PiPr₃)₂] with bis(ethynyl)‐substituted squaraine 8 . Spectroscopic and electrochemical measurements on 1 and its organic precursors 6 – 8 were performed to study the effect of the vinyl ruthenium “substituents,” particularly with respect to (poly)electrochromism. Attachment of the vinyl ruthenium moieties endows metal–organic squaraine 1 with two additional oxidation waves and lowers the first two oxidation potentials by approximately 300 mV with respect to its organic precursors. Squaraines 6 , 7 , 8 , and 1 strongly absorb at 648, 663, 656, or 709 nm. Although organic dyes 6 , 7 , and 8 fluoresce, no room‐temperature emission is observed for 1 . The radical cations and anions of 6 , 7 , 8 , and 1 as well as the doubly oxidized dications have been studied by IR and UV/Vis/NIR spectroelectrochemistry, and the ?/0/+/2+ redox sequences were found to be reversible in each case. Our results indicate that the 1^2?/?/0/+/2+ redox system constitutes a polyelectrochromic switch in which absorption in the visible or the near‐infrared range is reversibly turned off or shifted deep into the NIR. They also show that radical cation 1^.+ is an intrinsically delocalized system with only little contribution from the outer vinyl ruthenium tags to the oxidation process. Dication 1²⁺ constitutes a class‐II mixed‐valent system with two electronically different vinyl ruthenium moieties and has an open‐shell singlet electronic ground‐state structure. ESR and NMR spectra of chemically prepared 1^.+ and 1²⁺ corroborate these results. It has also emerged that reduction involves an orbital that is strongly delocalized across the entire squaraine π system and strongly affects the peripheral vinyl ruthenium sites.