An investigation of the germylene addition reaction, GeH2+C2H2: Time-resolved gas-phase kinetic studies and quantum chemical calculations of the reaction energy surface

Time resolved studies of germylene, GeH2, generated by laser flash photolysis of 3,4-dimethylgermacyclopentene-3, have been carried out to obtain rate constants for its bimolecular reaction with acetylene, C2H2. The reaction was studied in the gas-phase over the pressure range 1-100 Tort, with SF6 as bath gas, at 5 temperatures in the range 297-553 K. The reaction showed a very slight pressure dependence at higher temperatures. The high pressure rate constants (obtained by extrapolation at the three higher temperatures) gave the Arrhenius equation: log(k(infinity)/cm(3) molecule(-1) s(-1)) (-10.94 +/- 0.05) + (6.10 +/- 0.36 kJ mol(-1))/RTln10. These Arrhenius parameters are consistent with a fast reaction occurring at approximately 30% of the collision rate at 298 K. Quantum chemical calculations (both DFT and ab initio G2//B3LYP and G2//QCISD) of the GeC2H4 potential energy surface (PES), show that GeH2 + C2H2 react initially to form germirene which can isomerise to vinylgermylene with a relatively low barrier. RRKM modelling, based on a loose association transition state, but assuming vinylgermylene is the end product (used in combination with a weak collisional deactivation model) predicts a strong pressure dependence using the calculated energies, in conflict with the experimental evidence. The detailed GeC2H4 PES shows considerable complexity with ten other accessible stable minima (B3LYP level), the three most stable of which are all germylenes. Routes through this complex surface were examined in detail. The only product combination which appears capable of satisfying the (P-3) + C2H4.C2H4 was confirmed as a product by GC observed lack of a strong pressure dependence is Ge(P-3) + C2H4. C2H4 was confirmed as a product by GC analysis. Although the formation of these products are shown to be possible by singlet-triplet curve crossing during dissociation of 1-germiranylidene (1-germacyclopropylidene), it seems more likely (on thermochernical grounds) that the triplet biradical, (GeCH2CH2.)-Ge-., is the immediate product precursor. Comparisons are made with the reaction of SiH2 with C2H2.

The addition reaction between silylene and ethyne: further isotope studies, pressure dependence studies, and quantum chemical calculations

Time-resolved kinetic studies of the reaction of dideutero-silylene, SiD2, generated by laser flash photolysis of phenylsilane-d(3), have been carried out to obtain rate constants for its bimolecular reaction with C2H2. The reaction was studied in the gas phase over the pressure range 1-100 Torr in SF6 bath gas, at five temperatures in the range 297-600 K. The second-order rate constants obtained by extrapolation to the high-pressure limits at each temperature fitted the Arrhenius equation log(k(infinity)/cm(3) molecule(-1) s(-1)) = (-10.05 +/- 0.05) + (3.43 +/- 0.36 kJ mol(-1))/RT ln 10. The rate constants were used to obtain a comprehensive set of isotope effects by comparison with earlier obtained rate constants for the reactions of SiH2 with C2H2 and C2D2. Additionally, pressure-dependent rate constants for the reaction of SiH2 with C2H2 in the presence of He (1-100 Tort) were obtained at 300, 399, and 613 K. Quantum chemical (ab initio) calculations of the SiC2H4 reaction system at the G3 level support the initial formation of silirene, which rapidly isomerizes to ethynylsilane as the major pathway. Reversible formation of vinylsilylene is also an important process. The calculations also indicate the involvement of several other intermediates, not previously suggested in the mechanism. RRKM calculations are in semiquantitative agreement with the pressure dependences and isotope effects suggested by the ab initio calculations, but residual discrepancies suggest the possible involvement of the minor reaction channel, SiH2 + C2H2 - SWPO + C2H4. The results are compared and contrasted with previous studies of this reaction system.

Time-resolved gas-phase kinetic study of the germylene addition reaction, GeH2 + C2D2

Time-resolved studies of germylene, GeH2, generated by laser. ash photolysis of 3,4-dimethyl-1-germacyclopent-3-ene, have been carried out to obtain rate coefficients for its bimolecular reaction with C2D2. The reaction was studied in the gas phase, mainly at a total pressure of 1.3 kPa (in SF6 bath gas) at five temperatures in the range 298-558 K. Pressure variation measurements over the range 0.13-13 kPa ( SF6) at 298, 397 and 558 K revealed a small pressure dependence but only at 558 K. After correction for this, the second-order rate coefficients gave the Arrhenius equation: log(k(infinity)/cm(3) molecule(-1) s(-1)) = (-10.96 +/- 0.05) + ( 6.16 +/- 0.37 kJ mol(-1))/RT ln 10 Comparison with the reaction of GeH2 + C2H2 (studied earlier) showed a similar behaviour with almost identical rate coefficients. The lack of a significant isotope effect is consistent with a rate-determining addition process and is explained by irreversible decomposition of the reaction intermediate to give Ge(P-3) + C2H4. This result contrasts with that for GeH2 + C2H4/C2D4 and those for the analogous silylene reactions. The underlying reasons for this are discussed.

Gas-phase kinetics of chlorosilylene reactions II. ClSiH + C2H4: absolute rate measurements and quantum chemical and RRKM calculations for the prototype pi addition reaction

Time-resolved studies of chlorosilylene, ClSiH, generated by the 193 nm laser flash photolysis of 1-chloro-1-silacyclopent-3-ene, are carried out to obtain rate constants for its bimolecular reaction with ethene, C2H4, in the gas-phase. The reaction is studied over the pressure range 0.13-13.3 kPa (with added SF6) at five temperatures in the range 296-562 K. The second order rate constants, obtained by extrapolation to the high pressure limits at each temperature, fitted the Arrhenius equation: log(k(infinity)/cm(3) molecule(-1) s(-1))=(-10.55 +/- 0.10) + (3.86 +/- 0.70) kJ mol(-1)/RT ln10. The Arrhenius parameters correspond to a loose transition state and the rate constant at room temperature is 43% of that for SiH2 + C2H4, showing that the deactivating effect of Cl-for-H substitution in the silylene is not large. Quantum chemical calculations of the potential energy surface for this reaction at the G3MP2//B3LYP level show that, as well as 1-chlorosilirane, ethylchlorosilylene is a viable product. The calculations reveal how the added effect of the Cl atom on the divalent state stabilisation of ClSiH influences the course of this reaction. RRKM calculations of the reaction pressure dependence suggest that ethylchlorosilylene should be the main product. The results are compared and contrasted with those of SiH2 and SiCl2 with C2H4.

Time-resolved gas-phase kinetic study of the germylene addition reaction, CH3C CCH3

Time-resolved kinetic studies of the reaction of germylene, GeH2, generated by laser. ash photolysis of 3,4-dimethyl-1-germacyclopent-3-ene, have been carried out to obtain rate constants for its bimolecular reaction with 2-butyne, CH3C CCH3. The reaction was studied in the gas phase over the pressure range 1-100 Torr in SF6 bath gas, at five temperatures in the range 300-556 K. The second order rate constants obtained by extrapolation to the high pressure limits at each temperature, fitted the Arrhenius equation: log(k(infinity)/cm(3) molecule(-1) s(-1)) = (-10.46 +/- 10.06) + (5.16 +/- 10.47) kJ mol(-1)/ RT ln 10 Calculations of the energy surface of the GeC4H8 reaction system were carried out employing the additivity principle, by combining previous quantum chemical calculations of related reaction systems. These support formation of 1,2-dimethylvinylgermylene (rather than 2,3-dimethylgermirene) as the end product. RRKM calculations of the pressure dependence of the reaction are in reasonable agreement with this finding. The reactions of GeH2 with C2H2 and with CH3CRCCH3 are compared and contrasted.

Mechanistic study of the addition reaction of TeCl(4) to alkynes: Participation of TeCl(3) centered-radical

The mechanism of the addition reaction of TeCl(4) to alkynes was indirectly established by the detection of TeCl(3) centered radicals using EPR spin trapping, ESI-MS and ESI-MS/MS characterization. Crown Copyright (C) 2008 Published by Elsevier B. V. All rights reserved.

Revisiting the addition reaction of TeCl4 to alkynes: the crystal structure and docking studies of 1-chloro-2-trichlorotelluro-3-phenyl-propen-2-ol

Tellurium tetrachloride adds to alkynes via two pathways: a concerted syn addition, that yields Z-tri- and tetra-substituted alkenes or by an anti addition that yields E-alkenes. The mechanistic aspects of these divergent pathways have been reevaluated at the light of crystallographic data. The molecules, of the title compound, in the crystal, are associated in a helical fashion with a Te...Te pitch of 6.3492(6) angstrom. As it exhibits inhibitory activity for cathepsin B and in order to gain more insight of the inhibition mechanism, a docking study was undertaken providing insight on why organic telluranes are more efficient inhibitors than inorganic ones as AS-101. (c) 2006 Elsevier B.V. All rights reserved.

Metallic chalcogenolates mediated modular Michael-aldol cascade reaction: an easy route to multi-functionalized chalcogenides and Morita-Baylis-Hillman adducts

Chalcogenolate mediated Michael-aldol cascade reactions consists of a very efficient route to multi-functionalized gamma-hydroxichalcogenides. Although, when selenolates are employed, these gamma-hydroxichalcogenides can be readily converted into the corresponding Morita-Baylis-Hillman adducts by oxidative elimination of the selenium moiety. In this context, herein we present a complete study on the scope and limitations of this reaction. (C) 2012 Elsevier Ltd. All rights reserved.

Computational study on the asymmetric aminocatalysed Michael addition reaction of cyclohexanone to trans–β–nitrostyrene

Asymmetric organocatalysed reactions are one of the most fascinating synthetic strategies which one can adopt in order to induct a desired chirality into a reaction product. From all the possible practical applications of small organic molecules in catalytic reaction, amine–based catalysis has attracted a lot of attention during the past two decades. The high interest in asymmetric aminocatalytic pathways is to account to the huge variety of carbonyl compounds that can be functionalized by many different reactions of their corresponding chiral–enamine or –iminium ion as activated nucleophile and electrophile, respectively. Starting from the employment of L–Proline, many useful substrates have been proposed in order to further enhance the catalytic performances of these reaction in terms of enantiomeric excess values, yield, conversion of the substrate and turnover number. In particular, in the last decade the use of chiral and quasi–enantiomeric primary amine species has got a lot of attention in the field. Contemporaneously, many studies have been carried out in order to highlight the mechanism through which these kinds of substrates induct chirality into the desired products. In this scenario, computational chemistry has played a crucial role due to the possibility of simulating and studying any kind of reaction and the transition state structures involved. In the present work the transition state geometries of primary amine–catalysed Michael addition reaction of cyclohexanone to trans–β–nitrostyrene with different organic acid cocatalysts has been studied through different computational techniques such as density functional theory based quantum mechanics calculation and force–field directed molecular simulations.

Estudo da adição aldólica do éster terc-butílico da n-(difenilmetileno)glicina a alguns aldeídos aromáticos

As reações de adição aldólica entre a cetimina 1 e aldeídos aromáticos foram inicialmente efetuadas à temperatura ambiente, em sistema bifásico constituído por uma fase aquosa básica (KOH 10% ou NaOH 5% m/v) e por uma fase orgânica (aldeído), na ausência de solventes e de catalisadores, observando-se baixa conversão em produto. Porém, quando se utilizou o catalisador aliquat®-336, foi possível reduzir a concentração da base (NaOH 1%), com conversão total da imina em produto que, na maioria dos casos, era uma mistura de duas oxazolidinas isoméricas de estereoquímica cis e trans. Esses compostos puderam ser isolados e purificados por recristalização de etanol ou metanol. Em todas as reações efetuadas com benzaldeído, m-clorobenzaldeído e p-nitrobenzaldeído, não se observou excesso diastereomérico significativo. No entanto, as reações com p-clorobenzaldeído mostraram-se diastereosseletivas, conduzindo, à temperatura ambiente, quase que exclusivamente à oxazolidina de estereoquímica cis. A comparação entre o resultado de reações efetuadas a curto e longo tempo de reação, ou em diferentes temperaturas, permitiu concluir que o aldol de estereoquímica anti é o produto cinético, o qual se transforma lentamente na oxazolidina cis. O produto termodinâmico (aldol syn) cicliza rapidamente, não sendo observado nos espectros de RMN de H dos produtos brutos de reação, mas sim seu produto ciclizado, a oxazolidina trans. Tentativas de obter os produtos de reação com excesso enantiomérico, pelo emprego de catalisadores de transferência de fase assimétricos, não foram bem sucedidas.

De Novo Design of secondary structures: Synthesis and conformational studies

Chemists have long sought to extrapolate the power of biological catalysis and recognition to synthetic systems. These efforts have focused largely on low molecular weight catalysts and receptors; however, biological systems themselves rely almost exclusively on polymers, proteins and RNA, to perform complex chemical functions. Proteins and RNA are unique in their ability to adopt compact, well-ordered conformations, and specific folding provides precise spatial orientation of the functional groups that comprise the “active site”. These features suggest that identification of new polymer backbones with discrete and predictable folding propensities (“foldamers”) will provide a basis for design of molecular machines with unique capabilities. The foldamer approach complements current efforts to design unnatural properties into polypeptides and polynucleotides. The aim of this thesis is the synthesis and conformational studies of new classes of foldamers, using a peptidomimetic approach. Moreover their attitude to be utilized as ionophores, catalysts, and nanobiomaterials were analyzed in solution and in the solid state. This thesis is divided in thematically chapters that are reported below. It begins with a very general introduction (page 4) which is useful, but not strictly necessary, to the expert reader. It is worth mentioning that paragraph I.3 (page 22) is the starting point of this work and paragraph I.5 (page 32) isrequired to better understand the results of chapters 4 and 5. In chapter 1 (page 39) is reported the synthesis and conformational analysis of a novel class of foldamers containing (S)-β3-homophenylglycine [(S)-β3-hPhg] and D- 4-carboxy-oxazolidin-2-one (D-Oxd) residues in alternate order is reported. The experimental conformational analysis performed in solution by IR, 1HNMR, and CD spectroscopy unambiguously proved that these oligomers fold into ordered structures with increasing sequence length. Theoretical calculations employing ab initio MO theory suggest a helix with 11-membered hydrogenbonded rings as the preferred secondary structure type. The novel structures enrich the field of peptidic foldamers and might be useful in the mimicry of native peptides. In chapter 2 cyclo-(L-Ala-D-Oxd)3 and cyclo-(L-Ala-DOxd) 4 were prepared in the liquid phase with good overall yields and were utilized for bivalent ions chelation (Ca2+, Mg2+, Cu2+, Zn2+ and Hg2+); their chelation skill was analyzed with ESI-MS, CD and 1HNMR techniques and the best results were obtained with cyclo-(L-Ala-D-Oxd)3 and Mg2+ or Ca2+. Chapter 3 describes an application of oligopeptides as catalysts for aldol reactions. Paragraph 3.1 concerns the use of prolinamides as catalysts of the cross aldol addition of hydroxyacetone to aromatic aldeydes, whereas paragraphs 3.2 and 3.3 are about the catalyzed aldol addition of acetone to isatins. By means of DFT and AIM calculations, the steric and stereoelectronic effects that control the enantioselectivity in the cross-aldol addition of acetone to isatin catalysed by L-proline have been studied, also in the presence of small quantities of water. In chapter 4 is reported the synthesis and the analysis of a new fiber-like material, obtained from the selfaggregation of the dipeptide Boc-L-Phe-D-Oxd-OBn, which spontaneously forms uniform fibers consisting of parallel infinite linear chains arising from singleintermolecular N-H···O=C hydrogen bonds. This is the absolute borderline case of a parallel β-sheet structure. Longer oligomers of the same series with general formula Boc-(L-Phe-D-Oxd)n-OBn (where n = 2-5), are described in chapter 5. Their properties in solution and in the solid state were analyzed, in correlation with their attitude to form intramolecular hydrogen bond. In chapter 6 is reported the synthesis of imidazolidin-2- one-4-carboxylate and (tetrahydro)-pyrimidin-2-one-5- carboxylate, via an efficient modification of the Hofmann rearrangement. The reaction affords the desired compounds from protected asparagine or glutamine in good to high yield, using PhI(OAc)2 as source of iodine(III).

Enantioselective Reactions Promoted by Organocatalytic Species From The Natural Chiral Pool

During the course of my Ph.D. in the laboratories directed by Prof. Alfredo Ricci at the Department of Organic Chemistry “A. Mangini” of the University of Bologna, I was involved in the study and the application of a number of organocatalytic systems, all coming from the natural chiral pool. The first part of this thesis will be devoted to new homogeneous organocatalytic reactions promoted by Cinchona alkaloid-based organocatalysts. Quinine based catalysts were found to be a very effective catalyst for Diels-Alder reactions involving 3-vinylindoles. Excellent results in terms of yields and enantioselectivities were achieved, outlining also a remarkable organocatalytic operational mode mimicking enzymatic catalysis. The same reaction with 2-vinylindoles showed a completely different behaviour resulting in an unusual resolution-type process. The asymmetric formal [3+2] cycloaddition with in situ generated N-carbamoyl nitrones using Cinchona-derived quaternary ammonium salts as versatile catalysts under phase transfer conditions, outlines another application in organocatalysis of this class of alkaloids. During the seven months stage in the Prof. Helma Wennemers’ group at the Department of Chemistry of the University of Basel (Switzerland) I have been involved in organocatalysis promoted by oligopeptides. My contribution regarded the 1,4-addition reaction of aldehydes to nitroolefins. In the work performed at the Department of Organic Chemistry “A. Mangini” of the University of Bologna, in collaboration with the ‘Institut Charles Gerhardt-Montpellier, of Montpellier (France) the possibility of performing for the first time heterogeneous organocatalysis by using a natural polysaccharide biopolymer as the source of chirality was disclosed. With chitosan, derived from deacetylation of chitin, a highly enantioselective heterogeneous organocatalytic aldol reaction could be performed. The use of an eco-friendly medium such as water, the recyclability of the catalytic specie and the renewable nature of the polysaccharide are assets of this new approach in organocatalysis and open interesting perspectives for the use of biopolymers.

Uma nova metodologia para a síntese de modelos de lignina a partir de reações de inserção O-H entre fenóis de α-aril diazocetonas

A biomassa lignicelulósica tem sua estrutura composta por celulose, hemicelulose e lignina. Dentre essas, a lignina tem se mostrado interessante por ser uma fonte precursora sustentável de fragmentos aromáticos antes obtidos apenas de combustíveis fósseis. Sua estrutura é composta por resíduos de fenilpropanóides p-hidroxibenzeno (H), guaiacil (G) e siringil (S) unidas por ligações C–C e C–O–C em que a ligação β–O–4 é a predominante (mais de 50%). Devido à sua complexidade estrutural e conformacional, a clivagem de suas ligações é pouco seletiva e a caracterização dos fragmentos resultantes é complexa. Uma estratégia comumente empregada para evitar esses desafios é o uso de modelos mais simples. Entretanto, poucas metodologias são reportadas na literatura para a sua síntese e a maioria delas envolve o emprego de halocetonas. O presente trabalho desenvolveu duas novas metodologias promissoras para síntese desses oligômeros, contendo ligação β–O–4 por meio da química de diazo: (a) reação de inserção O–H entre fenol e α–aril diazocetonas, e (b) compostos α–diazo β-cetoéster. Ademais, a utilização de monômeros contendo a função fenol e diazocetona no mesmo anel permitiria a síntese de cadeias de diversos tamanhos em uma única etapa. Como ponto de partida para o estudo, limitou-se à síntese de dímeros, visando entender a reação de inserção O–H. Os produtos desejados foram obtidos em rendimentos de 27–51% após catálise com Cu(hfac)2. Por fim, os modelos de lignina propriamente ditos foram sintetizados após simples adição aldólica e redução em rendimentos globais de 51–78%. Os estudos envolvendo a inserção de fenol em α–diazo β-cetoéster mostraram resultados promissores, corroborando para uma nova estratégia sintética para a obtenção de modelos de lignina. Novos estudos em nosso laboratório estão sendo desenvolvidos para se obter resultados mais conclusivos.

Solvent-Induced Reversal of Enantioselectivity in the Synthesis of Succinimides by the Addition of Aldehydes to Maleimides Catalysed by Carbamate-Monoprotected 1,2-Diamines

A simple change in the polarity of the solvent allows both enantiomers of substituted succinimides to be obtained in the enantioselective conjugate addition reaction of aldehydes, mainly α,α-disubstituted, to maleimides catalysed by chiral carbamate-monoprotected trans-cyclohexane-1,2-diamines. Using a single enantiomer of the organocatalyst, both enantiomers of the resulting Michael adducts are obtained in high yields by simply changing the reaction solvent from aqueous DMF (up to 84 % ee) to chloroform (up to 86 % ee). Theoretical calculations are used to explain this uncommon reversal of the enantioselectivity; two transition state orientations of different polarities are differently favoured in polar or nonpolar solvents.