Showing papers on "Intramolecular force published in 2011"
TL;DR: This critical review focuses on metalloporphyrin-catalysed saturated C-H bond functionalisation reported since the year 2000, including C-O, C-N and C-C bond formation via hydroxylation, amination and carbenoid insertion, respectively, together with a brief description of previous achievements.
Abstract: The recent surge of interest in metal-catalysed C-H bond functionalisation reactions reflects the importance of such reactions in biomimetic studies and organic synthesis. This critical review focuses on metalloporphyrin-catalysed saturated C-H bond functionalisation reported since the year 2000, including C-O, C-N and C-C bond formation via hydroxylation, amination and carbenoid insertion, respectively, together with a brief description of previous achievements in this area. Among the metalloporphyrin-catalysed reactions highlighted herein are the hydroxylation of steroids, cycloalkanes and benzylic hydrocarbons; intermolecular amination of steroids, cycloalkanes and benzylic or allylic hydrocarbons; intramolecular amination of sulfamate esters and organic azides; intermolecular carbenoid insertion into benzylic, allylic or alkane C-H bonds; and intramolecular carbenoid C-H insertion of tosylhydrazones. These metalloporphyrin-catalysed saturated C-H bond functionalisation reactions feature high regio-, diastereo- or enantioselectivity and/or high product turnover numbers. Mechanistic studies suggest the involvement of metal-oxo, -imido (or nitrene), and -carbene porphyrin complexes in the reactions. The reactivity of such metal-ligand multiple bonded species towards saturated C-H bonds, including mechanistic studies through both experimental and theoretical means, is also discussed (244 references).
503 citations
TL;DR: The copper species is proposed to catalytically activate the hypervalent iodine(III) oxidants to give a more diverse range of products in good to excellent yields.
Abstract: New synthetic procedures for intramolecular oxidative C-N bond formation have been developed for the preparation of carbazoles starting from N-substituted amidobiphenyls under either Cu-catalyzed or metal-free conditions using hypervalent iodine(III) as an oxidant. Whereas iodobenzene diacetate or bis(trifluoroacetoxy)iodobenzene alone undergoes the reaction to provide carbazole products in moderate to low yields, combined use of copper(II) triflate and the iodine(III) species significantly improves the reaction efficiency, giving a more diverse range of products in good to excellent yields. On the basis of mechanistic studies including kinetic profile, isotope effects, and radical inhibition experiments, the copper species is proposed to catalytically activate the hypervalent iodine(III) oxidants. The synthetic utility of the present approach was nicely demonstrated in a direct synthesis of indolo[3,2-b]carbazole utilizing a double C-N bond formation.
446 citations
TL;DR: In this article, the authors report ab initio path integral molecular dynamics studies on the quantum nature of the hydrogen bond and show that quantum nuclear effects weaken weak hydrogen bonds but strengthen relatively strong ones.
Abstract: Hydrogen bonds are weak, generally intermolecular bonds, which hold much of soft matter together as well as the condensed phases of water, network liquids, and many ferroelectric crystals. The small mass of hydrogen means that they are inherently quantum mechanical in nature, and effects such as zero-point motion and tunneling must be considered, though all too often these effects are not considered. As a prominent example, a clear picture for the impact of quantum nuclear effects on the strength of hydrogen bonds and consequently the structure of hydrogen bonded systems is still absent. Here, we report ab initio path integral molecular dynamics studies on the quantum nature of the hydrogen bond. Through a systematic examination of a wide range of hydrogen bonded systems we show that quantum nuclear effects weaken weak hydrogen bonds but strengthen relatively strong ones. This simple correlation arises from a competition between anharmonic intermolecular bond bending and intramolecular bond stretching. A simple rule of thumb is provided that enables predictions to be made for hydrogen bonded materials in general with merely classical knowledge (such as hydrogen bond strength or hydrogen bond length). Our work rationalizes the influence of quantum nuclear effects, which can result in either weakening or strengthening of the hydrogen bonds, and the corresponding structures, across a broad range of hydrogen bonded materials. Furthermore, it highlights the need to allow flexible molecules when anharmonic potentials are used in force field-based studies of quantum nuclear effects.
363 citations
TL;DR: In this paper, an efficient, atom-economical, environmentally friendly organocatalytic synthesis of carbazole derivatives is presented by intramolecular C-H amination of N-acetyl o-arylanilines (I, (III).
Abstract: An efficient, atom-economical, environmentally friendly organocatalytic synthesis of carbazole derivatives is presented by intramolecular C—H amination of N-acetyl o-arylanilines (I), (III).
332 citations
TL;DR: The preparation of hydrocarbons with extremely long C–C bonds (up to 1.704 Å) is reported, the longest such bonds observed so far in alkanes, and the prepared compounds are unexpectedly stable—noticeable decomposition occurs only above 200 °C.
Abstract: The synthesis of alkane hydrocarbons containing extremely long carbon–carbon (C–C) bonds, the longest observed in alkanes to date, is reported. Long C–C bonds are usually weaker than short ones, but these new alkanes are surprisingly stable, with decomposition occurring only above 200 °C. Quantum mechanical calculations show that, remarkably, the compounds are stabilized by attractive interactions between bulky groups at either end of the long C–C bonds. The stabilizing interactions observed in these compounds could prove useful in the development of new materials that utilize attractive dispersion interactions. Steric effects in chemistry are a consequence of the space required to accommodate the atoms and groups within a molecule, and are often thought to be dominated by repulsive forces arising from overlapping electron densities (Pauli repulsion). An appreciation of attractive interactions such as van der Waals forces (which include London dispersion forces) is necessary to understand chemical bonding and reactivity fully. This is evident from, for example, the strongly debated origin of the higher stability of branched alkanes relative to linear alkanes1,2 and the possibility of constructing hydrocarbons with extraordinarily long C–C single bonds through steric crowding3. Although empirical bond distance/bond strength relationships have been established for C–C bonds4 (longer C–C bonds have smaller bond dissociation energies), these have no present theoretical basis5. Nevertheless, these empirical considerations are fundamental to structural and energetic evaluations in chemistry6,7, as summarized by Pauling8 as early as 1960 and confirmed more recently4. Here we report the preparation of hydrocarbons with extremely long C–C bonds (up to 1.704 A), the longest such bonds observed so far in alkanes. The prepared compounds are unexpectedly stable—noticeable decomposition occurs only above 200 °C. We prepared the alkanes by coupling nanometre-sized, diamond-like, highly rigid structures known as diamondoids9. The extraordinary stability of the coupling products is due to overall attractive dispersion interactions between the intramolecular H•••H contact surfaces, as is evident from density functional theory computations with10 and without inclusion of dispersion corrections.
331 citations
TL;DR: Time-resolved microwave conductivity measurements prove that the intrinsic hole mobility of A is comparable to that of rubrene, one of the most commonly used organic semiconductors, indicating that BN-substituted PAHs are potential candidates for organic electronic materials.
Abstract: A tandem intramolecular electrophilic arene borylation reaction has been developed for the synthesis of BN-fused polycyclic aromatic compounds such as 4b-aza-12b-boradibenzo[g,p]chrysene (A) and 8b,11b-diaza-19b,22b-diborahexabenzo[a,c,fg,j,l,op]tetracene. These compounds adopt a twisted conformation, which results in a tight and offset face-to-face stacking array in the solid state. Time-resolved microwave conductivity measurements prove that the intrinsic hole mobility of A is comparable to that of rubrene, one of the most commonly used organic semiconductors, indicating that BN-substituted PAHs are potential candidates for organic electronic materials.
251 citations
TL;DR: NMR based evidence for intramolecular hydrogen bonding in several ‘beyond rule of five’ oral drugs is described and the propensity for these drugs to form intramolescular hydrogen bonds could be predicted for through modelling the lowest energy conformation in the gas phase.
Abstract: Utilising ‘beyond rule of five’ chemical space is becoming increasingly important in drug design, but is usually at odds with good oral absorption. The formation of intramolecular hydrogen bonds in drug molecules is hypothesised to shield polarity facilitating improved membrane permeability and intestinal absorption. NMR based evidence for intramolecular hydrogen bonding in several ‘beyond rule of five’ oral drugs is described. Furthermore, the propensity for these drugs to form intramolecular hydrogen bonds could be predicted for through modelling the lowest energy conformation in the gas phase. The modulation of apparent lipophilicity through intramolecular hydrogen bonding in these molecules is supported by intrinsic cell permeability and intestinal absorption data in rat and human.
238 citations
TL;DR: It is shown that phenyl cation equivalents, generated from otherwise unreactive aryl fluorides, allow extension of the Friedel-Crafts reaction to intramolecular aries couplings, and Silicon-fluorine bond formation expands the range of compounds that can be used in a reaction that forms carbon-carbon bonds.
Abstract: The venerable Friedel-Crafts reaction appends alkyl or acyl groups to aromatic rings through alkyl or acyl cation equivalents typically generated by Lewis acids. We show that phenyl cation equivalents, generated from otherwise unreactive aryl fluorides, allow extension of the Friedel-Crafts reaction to intramolecular aryl couplings. The enabling feature of this reaction is the exchange of carbon-fluorine for silicon-fluorine bond enthalpies; the reaction is activated by an intermediate silyl cation. Catalytic quantities of protons or silyl cations paired with weakly coordinating carborane counterions initiate the reactions, after which proton transfer in the final aromatization step regenerates the active silyl cation species by protodesilylation of a quaternary silane. The methodology allows the high-yield formation of a range of tailored polycyclic aromatic hydrocarbons and graphene fragments.
236 citations
TL;DR: Spirocyclohexadienone derivatives are obtained in high yields and enantioselectivities by intramolecular asymmetric allylic dearomatization of phenols bearing tethered allylic ethers as discussed by the authors.
Abstract: Spirocyclohexadienone derivatives are obtained in high yields and enantioselectivities by intramolecular asymmetric allylic dearomatization of phenols bearing tethered allylic ethers.
222 citations
TL;DR: This perspective reports on some of the main copper-catalyzed routes to the construction of the pyrrole and furan rings incorporated into the indole and benzo[b]furan systems, respectively.
Abstract: This perspective reports on some of the main copper-catalyzed routes to the construction of the pyrrole and furan rings incorporated into the indole and benzo[b]furan systems, respectively. The first part illustrates the synthesis of indoles through cyclizations of 2-alkynylanilid(n)es, preformed or generated in situ, and cyclizationsvia intramolecular N-arylation, N-vinylation, and C–C bond forming reactions. The second part illustrates the synthesis of benzo[b]furans through cyclizations of preformed 2-alkynylphenols, domino synthesis of 2-alkynylphenols/cyclization processes, and cyclizationsvia intramolecular O-arylation reactions.
216 citations
TL;DR: In this article, freely rotatable tetraphenylethene (TPE) was introduced to conventional luminophors quenches their light emissions in the solutions but endows the resultant molecules with aggregation-induced emission characteristics in the condensed phase due to the restriction of intramolecular rotation.
Abstract: Introduction of freely rotatable tetraphenylethene (TPE) to conventional luminophors quenches their light emissions in the solutions but endows the resultant molecules (TPEArs) with aggregation-induced emission characteristics in the condensed phase due to the restriction of intramolecular rotation. High fluorescence quantum yields up to 100% have been achieved in the films of TPEArs.
TL;DR: This review discusses and compares the three main N-arylation methods in their application to the synthesis of biologically active compounds: Palladium-catalysed Buchwald–Hartwig-type reactions, copper-mediated Ullmann-type and Chan–Lam-type N-ARYlation reactions.
Abstract: N-Arylated aliphatic and aromatic amines are important substituents in many biologically active compounds. In the last few years, transition-metal-mediated N-aryl bond formation has become a standard procedure for the introduction of amines into aromatic systems. While N-arylation of simple aromatic halides by simple amines works with many of the described methods in high yield, the reactions may require detailed optimization if applied to the synthesis of complex molecules with additional functional groups, such as natural products or drugs. We discuss and compare in this review the three main N-arylation methods in their application to the synthesis of biologically active compounds: Palladium-catalysed Buchwald–Hartwig-type reactions, copper-mediated Ullmann-type and Chan–Lam-type N-arylation reactions. The discussed examples show that palladium-catalysed reactions are favoured for large-scale applications and tolerate sterically demanding substituents on the coupling partners better than Chan–Lam reactions. Chan–Lam N-arylations are particularly mild and do not require additional ligands, which facilitates the work-up. However, reaction times can be very long. Ullmann- and Buchwald–Hartwig-type methods have been used in intramolecular reactions, giving access to complex ring structures. All three N-arylation methods have specific advantages and disadvantages that should be considered when selecting the reaction conditions for a desired C–N bond formation in the course of a total synthesis or drug synthesis.
TL;DR: An efficient method for the synthesis of 4-amino-2-aryl(alkyl)quinazolines from readily available N-arylamidines and isonitriles via palladium-catalyzed intramolecular aryl C-H amidination by isonitrile insertion has been developed.
TL;DR: Six 2-quinolones, which bear a terminal alkene linked by a three- or four-membered tether to carbon atom C4 of the quinolone, were synthesized and subjected to an intramolecular [2 + 2]-photocycloaddition, finding the xanthone-based organocatalyst proved to be superior as compared to the respective benzophenone.
Abstract: Six 2-quinolones, which bear a terminal alkene linked by a three- or four-membered tether to carbon atom C4 of the quinolone, were synthesized and subjected to an intramolecular [2 + 2]-photocycloaddition. The reaction delivered the respective products in high yields (78–99%) and with good regioselectivity in favor of the straight isomer. If conducted in the presence of a chiral hydrogen-bonding template (2.5 equiv) at low temperature in toluene as the solvent, the reaction proceeded enantioselectively (83–94% ee). An organocatalytic reaction was achieved when employing a chiral hydrogen-bonding template with an attached sensitizing unit (benzophenone or xanthone). The xanthone-based organocatalyst proved to be superior as compared to the respective benzophenone. Closer inspection revealed that the reaction of 4-(pent-4-enyloxy)quinolone leading to a six-membered ring, annelated to the cyclobutane, was less enantioselective (up to 41% ee with 30 mol % catalyst) than the reaction of 4-(but-3-enyloxy)quinol...
TL;DR: In this article, the authors presented a method to predict (subcooled) liquid pure compound vapour pressure p 0 of organic molecules that requires only molecular structure as input, which is applicable to zero-, mono-and polyfunctional molecules.
Abstract: . We present EVAPORATION (Estimation of VApour Pressure of ORganics, Accounting for Temperature, Intramolecular, and Non-additivity effects), a method to predict (subcooled) liquid pure compound vapour pressure p 0 of organic molecules that requires only molecular structure as input. The method is applicable to zero-, mono- and polyfunctional molecules. A simple formula to describe log 10 p 0 ( T ) is employed, that takes into account both a wide temperature dependence and the non-additivity of functional groups. In order to match the recent data on functionalised diacids an empirical modification to the method was introduced. Contributions due to carbon skeleton, functional groups, and intramolecular interaction between groups are included. Molecules typically originating from oxidation of biogenic molecules are within the scope of this method: aldehydes, ketones, alcohols, ethers, esters, nitrates, acids, peroxides, hydroperoxides, peroxy acyl nitrates and peracids. Therefore the method is especially suited to describe compounds forming secondary organic aerosol (SOA).
TL;DR: It was found that there are not any distinct differences between RAHBs and the other intramolecular hydrogen bonds, and the CVB index based on the ELF method as well as the total electron energy density at the bond critical point of the proton-acceptor distance may be treated as universal descriptors of the hydrogen bond strength.
Abstract: B3LYP/aug-cc-pVTZ calculations were performed on the species with intramolecular O–H···O hydrogen bonds. The Quantum Theory of Atoms in Molecules (QTAIM) and the Electron Localization Function (ELF) method were applied to analyze these interactions. Numerous relationships between ELF and QTAIM parameters were found. It is interesting that the CVB index based on the ELF method as well as the total electron energy density at the bond critical point of the proton–acceptor distance (Hbcp) may be treated as universal descriptors of the hydrogen bond strength, they are also useful to estimate the covalent character of this interaction. There are so-called resonance-assisted hydrogen bonds (RAHBs) among the species analyzed here. It was found that there are not any distinct differences between RAHBs and the other intramolecular hydrogen bonds.
TL;DR: A straightforward, efficient, and more sustainable copper-catalyzed method has been developed for intramolecular N-arylation providing the benzimidazole ring system, exclusively carried out in water, rendering the methodology highly valuable from both environmental and economical points of view.
Abstract: A straightforward, efficient, and more sustainable copper-catalyzed method has been developed for intramolecular N-arylation providing the benzimidazole ring system. With Cu2O (5 mol %) as the catalyst, DMEDA (10 mol %) as the ligand, and K2CO3 as the base, this protocol was applied to synthesize a small library of benzimidazoles in high yields. Remarkably, the reaction was exclusively carried out in water, rendering the methodology highly valuable from both environmental and economical points of view.
TL;DR: Potassium tert-butoxide mediated intramolecular cyclization of aryl ethers, amines, and amides was efficiently performed under microwave irradiation to provide the corresponding products in high regioisomeric ratios.
TL;DR: An efficient synthesis of quinazolin-4(3H)-ones from N-arylamidines, through palladium-catalyzed intramolecular C(sp(2))-H carboxamidation, has been developed and features atom-economy and step-efficiency.
Abstract: An efficient synthesis of quinazolin-4(3H)-ones from N-arylamidines, through palladium-catalyzed intramolecular C(sp2)–H carboxamidation, has been developed. The reaction, carried out in the presence of 1.0 equiv of CuO as oxidant under atmospheric pressure of CO, provides diversified 2-aryl(alkyl)quinazolin-4(3H)-ones in reasonable to good yields from N-arylamidines, which are readily derived from anilines and nitriles. Compared with existing approaches to quinazolin-4(3H)-ones, the current strategy features atom-economy and step-efficiency.
TL;DR: The [Co(P2)]-based intramolecular metalloradical cyclopropanation provides convenient access to densely functionalized 3-oxabicyclo[3.1.0]hexan-2-one derivatives bearing three contiguous quaternary and tertiary chiral centers with high enantiomeric purity.
Abstract: 3,5-Di(t)Bu-QingPhyrin, a new D(2)-symmetric chiral porphyrin derived from a chiral cyclopropanecarboxamide containing two contiguous stereocenters, has been developed using an iterative approach based on Co(II)-catalyzed asymmetric cyclopropanation of alkenes. The Co(II) complex of 3,5-Di(t)Bu-QingPhyrin, [Co(P2)], has proved to be a general and effective catalyst for asymmetric intramolecular cyclopropanation of various allylic diazoacetates (especially including those with α-acceptor substituents) in high yields with excellent stereoselectivities. The [Co(P2)]-based intramolecular metalloradical cyclopropanation provides convenient access to densely functionalized 3-oxabicyclo[3.1.0]hexan-2-one derivatives bearing three contiguous quaternary and tertiary chiral centers with high enantiomeric purity.
TL;DR: An oxidative C-H coupling is described for medium-ring synthesis and it is shown that this coupling can be modified for high-performance liquid chromatography using Na6(CO3)(SO4)2, Na2SO4, and Na2CO3.
Abstract: An oxidative C-H coupling is described for medium-ring synthesis, e.g., I. [on SciFinder(R)]
TL;DR: Density functional theory calculations and molecular dynamics simulations support the experimental observations, suggesting metal-mediated intramolecular proton transfers between nitrogen atoms, with chair-to-boat isomerizations as the rate-limiting steps.
Abstract: Proton transport is ubiquitous in chemical and biological processes, including the reduction of dioxygen to water, the reduction of CO2 to formate, and the production/oxidation of hydrogen. In this work we describe intramolecular proton transfer between Ni and positioned pendant amines for the hydrogen oxidation electrocatalyst [Ni(PCy2NBn2H)2]2+ (PCy2NBn2 = 1,5-dibenzyl-3,7-dicyclohexyl-1,5-diaza-3,7-diphosphacyclooctane). Rate constants are determined by variable-temperature one-dimensional NMR techniques and two-dimensional EXSY experiments. Computational studies provide insight into the details of the proton movement and energetics of these complexes. Intramolecular proton exchange processes are observed for two of the three experimentally observable isomers of the doubly protonated Ni(0) complex, [Ni(PCy2NBn2H)2]2+, which have N–H bonds but no Ni–H bonds. For these two isomers, with pendant amines positioned endo to the Ni, the rate constants for proton exchange range from 104 to 105 s–1 at 25 °C, de...
TL;DR: Kinetic isotope effect experiments indicated that C-H bond cleavage is the rate-limiting step of the reaction of 2-Arylphenols under palladium catalysis.
TL;DR: A novel metal-free intramolecular oxidative decarboxylative coupling of primary α-amino acids with 2-aminobenzoketones with different quinazolines can be selectively obtained by various oxidants.
TL;DR: 'Salen' along: the iridium(III)-salen complex 1 efficiently catalyzes the title reaction of 2-ethylbenzenesulfonyl azides to give five-membered sultams with high enantioselectivity.
Abstract: 'Salen' along: the iridium(III)-salen complex 1 efficiently catalyzes the title reaction of 2-ethylbenzenesulfonyl azides to give five-membered sultams with high enantioselectivity. Other 2-alkyl-substitued substrates lead to five- and six-membered sultams with high enantioselectivity; the regioselectivity depends upon the substrate and the catalyst used. EDG=electron-donating group.
TL;DR: A series of new amphiphilic phosphonium materials that combine the electronic features of phospholes with self-assembly features of lipids were synthesized and revealed that both conjugated backbones and counteranions work together to organize the systems into different morphologies (liquid crystal/soft crystal).
Abstract: A series of new amphiphilic phosphonium materials that combine the electronic features of phospholes with self-assembly features of lipids were synthesized. Variable concentration/temperature and 2D NMR studies suggested that the systems undergo intramolecular conformation changes between a "closed" and "open" form that are triggered by intermolecular interactions. The amphiphilic features of the phospholium species also induce liquid crystalline and soft crystal phase behavior in the solid state, which was studied by differential scanning calorimetry (DSC), polarized optical microscopy (POM), and variable temperature powder X-ray diffraction (VT-PXRD). The studies revealed that both conjugated backbones and counteranions work together to organize the systems into different morphologies (liquid crystal/soft crystal). Dithieno[3,2-b:2',3'-d]phosphole-based compounds exhibit enhanced emission in the solid state and at low temperature in solution due to aggregation-induced enhanced emission (AIEE). Photoinduced electron transfer (PET) induced via the alkoxybenzyl group at the phosphonium center in the fused-ring systems can be effectively suppressed through intermolecular charge transfer (ICT) processes within the main scaffold of a nonfused system, which was confirmed by static and dynamic fluorescence spectroscopy. The dynamic features of these new materials also endow the systems with external-stimuli responsive photophysical properties that can be triggered by temperature and/or mechanical forces.
TL;DR: A practical iron-catalyzed intramolecular C-H amination reaction and its application in the synthesis of indole derivatives are presented.
TL;DR: The optimized geometry of BBC using density functional theory shows that the energetically favored chair conformation is not observed for central cyclohexanone ring and is found to possess a nearly 'half chair' conformation and shows less expansion of the angles and more rotation about the bonds.
TL;DR: It is shown, for the prototype system La-perovskites, that there is a "cyclic" behavior in the transition state characteristics upon change of the active transition metal of the oxide.
Abstract: Versatile Broensted-Evans-Polanyi (BEP) relations are found from density functional theory for a wide range of transition metal oxides including rutiles and perovskites. For oxides, the relation depends on the type of oxide, the active site and the dissociating molecule. The slope of the BEP relation is strongly coupled to the adsorbate geometry in the transition state. If it is final state-like the dissociative chemisorption energy can be considered as a descriptor for the dissociation. If it is initial state-like, on the other hand, the dissociative chemisorption energy is not suitable as descriptor for the dissociation. Dissociation of molecules with strong intramolecular bonds belong to the former and molecules with weak intramolecular bonds to the latter group. We show, for the prototype system La-perovskites, that there is a 'cyclic' behavior in the transition state characteristics upon change of the active transition metal of the oxide.
TL;DR: Dibenzophosphole oxides were obtained from secondary hydrophosphine oxides with a biphenyl group by dehydrogenation via phosphine-hydrogen and carbon-Hydrogen bond cleavage in the presence of a catalytic amount of palladium(II) acetate.
Abstract: Dibenzophosphole oxides were obtained from secondary hydrophosphine oxides with a biphenyl group by dehydrogenation via phosphine-hydrogen and carbon-hydrogen bond cleavage in the presence of a catalytic amount of palladium(II) acetate, Pd(OAc)(2). By using this reaction, a ladder-type dibenzophosphole oxide could also be synthesized by double intramolecular dehydrogenative cyclization.