Exo Double Bond Research Articles

Selective palladium-catalyzed functionalization of α-methylene butanolides

We describe an efficient and selective functionalization of α-methylene-γ-butyrolactone. The two-step sequence involves the preparation of bromomethylene butyrolactone 2 in good yield prior to a palladium-catalyzed coupling process. The latter allowed the installation of aryl, alkenyl, and alkynyl groups under Suzuki-Miyaura, Heck, and Sonogashira cross-coupling conditions. The reaction sequences involving Pd(dppf)Cl2-CsF, Pd(OAc)2-PPh3-Ag2CO3, Pd(PPh4)4-CuI-Et3N as the corresponding catalytic systems allow the preparation of an unprecedented panel of α-unsaturated substituted butyrolactones 4–16 ranging from moderate to excellent yields. In all cases, the E-configuration of the exo-double bond is retained from the starting materials to the targets, regardless of the nature of the substituent introduced.

Synthesis and Reactivity of Electron-Deficient 3-Vinylchromones

AbstractThe reported methods and data for the synthesis and reactivity of electron-deficient 3-vinylchromones containing electron-withdrawing­ groups at the exo-cyclic double bond are summarized and systematized for the first time. The main methods for obtaining these compounds are Knoevenagel condensation, Wittig reaction, and palladium-catalyzed cross-couplings. The most important chemical properties are transformations under the action of mono- and dinucleophiles, ambiphilic cyclizations, and cycloaddition reactions. The cross-conjugated and polyelectrophilic dienone system in 3-vinylchromones provides their high reactivity and makes these compounds valuable building blocks for the preparation of more complex heterocyclic systems. Chemical transformations of 3-vinylchromones usually begin with an attack of the C-2 atom and are accompanied by the opening of the pyrone ring followed by recyclization, in which the carbonyl group of chromone, an exo-double bond or a substituent on it can take part. The mechanisms of the reactions are discussed, the conditions for their implementation are described, and the yields of the resulting products are given. This review focuses on an analysis and generalization of the knowledge that has accumulated on the chemistry of electron-deficient 3-vinylchromones, mostly over the past 15 years.1 Introduction2 Synthesis of 3-Vinylchromones3 Reactions with Mononucleophiles4 Reactions with Dinucleophiles5 Ambiphilic Cyclization6 Cycloaddition Reactions7 Other Reactions8 Conclusion

Comparative Analysis of Ethylene/Diene Copolymerization and Ethylene/Propylene/Diene Terpolymerization Using Ansa-Zirconocene Catalyst with Alkylaluminum/Borate Activator: The Effect of Conjugated and Nonconjugated Dienes on Catalytic Behavior and Polymer Microstructure.

The copolymerization of ethylene‒diene conjugates (butadiene (BD), isoprene (IP) and nonconjugates (5-ethylidene-2-norbornene (ENB), vinyl norbornene VNB, 4-vinylcyclohexene (VCH) and 1, 4-hexadiene (HD)), and terpolymerization of ethylene-propylene-diene conjugates (BD, IP) and nonconjugates (ENB, VNB, VCH and HD) using two traditional catalysts of C2-symmetric metallocene—silylene-bridged rac-Me2Si(2-Me-4-Ph-Ind)2ZrCl2 (complex A) and ethylene-bridged rac-Et(Ind)2ZrCl2 (complex B)—with a [Ph3C][B(C6F5)4] borate/TIBA co-catalyst, were intensively studied. Compared to that in the copolymerization of ethylene diene, the catalytic activity was more significant in E/P/diene terpolymerization. We obtained a maximum yield of both metallocene catalysts with conjugated diene between 3.00 × 106 g/molMt·h and 5.00 × 106 g/molMt·h. ENB had the highest deactivation impact on complex A, and HD had the most substantial deactivation effect on complex B. A 1H NMR study suggests that dienes were incorporated into the co/ter polymers’ backbone through regioselectivity. ENB and VNB, inserted by the edo double bond, left the ethylidene double bond intact, so VCH had an exo double bond. Complex A’s methyl and phenyl groups rendered it structurally stable and exhibited a dihedral angle greater than that of complex B, resulting in 1, 2 isoprene insertion higher than 1, 4 isoprene that is usually incapable of polymerization coordination. High efficiency in terms of co- and ter- monomer incorporation with higher molecular weight was found for complex 1. The rate of incorporation of ethylene and propylene in the terpolymer backbone structure may also be altered by the conjugated and nonconjugated dienes. 13C-NMR, 1H-NMR, and GPC techniques were used to characterize the polymers obtained.

The oxidation mechanism of gas-phase ozonolysis of limonene in the atmosphere.

Limonene with endo- and exo-double bonds is a significant monoterpene in the atmosphere and has high reactivity towards O3. We investigated the atmospheric oxidation mechanism of limonene ozonolysis using a high level quantum chemistry calculation coupled with RRKM-ME kinetic simulation. The additions of O3 can take place at both the endo- and exo-double bonds with a branching ratio of 0.87 : 0.13, forming four major highly energized CIs* (named Syn-2a*, Syn-2b*, Anti-2b* and Anti-2c*) with the relative higher fractions of 0.21 : 0.35 : 0.27 : 0.11. A yield of 4% for Limona-ketone was obtained as well. For the unimolecular isomerization pathways of limonene + O3 → POZs → CIs* → SOZ, VHP, or dioxirane, five, one, or none of the internal rotations are treated as hindered internal rotors for CIs*. We obtained percentages of 0.59 : 0.18 : 0.14 in total for separate isomerization routes in the formation of VHPs, dioxirane and SOZs from CIs* using the fourth-order Runge-Kutta method. Additionally, a yield of ∼5% was acquired for stabilized CIs compiling the fractions of different addition routes. About ∼10% of stabilized Anti-2b would isomerize to VHP and 90% would isomerize to SOZs. Isomerization to VHPs dominates the fate of stabilized Syn-2a, Syn-2b and Anti-2c. The overall yield of OH radicals was 0.61. Our study suggested a yield of 0.17 for stabilized SOZs and 0.18 for dioxirane, although both their fates are ambiguous.

Prenylation and Dehydrogenation of a C2-Reversely Prenylated Diketopiperazine as a Branching Point in the Biosynthesis of Echinulin Family Alkaloids in Aspergillus ruber.

The echinulin family alkaloids can be grouped into three series depending on the number of the exo double bonds adjacent to the diketopiperazine core structure. Heterologous expression of the putative echinulin biosynthetic gene cluster from Aspergillus ruber in Aspergillus nidulans led to accumulation of echinulin without a double bond and neoechinulin A with one double bond (Δ10) as major products. Their analogues with a different number of prenyl moieties were detected as minor products. Neoechinulin B and analogues with two double bonds (Δ10,14) were not observed. Feeding experiments confirmed that the cytochrome P450 enzyme EchP450 only catalyzes the formation of the double bond between C10 and C11. Coincubation and substrate concentration dependent assays with the prenyltransferase EchPT2 revealed that the reversely C2-prenylated preechinulin without a double bond is a much better substrate than neoechinulin A. These results prove that preechinulin serves as a common substrate for the formation of echinulin by two regiospecific prenylation steps with EchPT2 or for EchP450 to introduce one double bond and subsequent prenylations with low regioselectivity.

Design, Synthesis and Biological Evaluation of 2‐(naphthoyl) iminothiazolidin‐4‐ones as Potential Anticancer Agents

AbstractA library of novel naphthyl bearing 2‐iminothiazolidin‐4‐ones (2‐ITZDs) (2 a–2 q) was designed and synthesized through a facile route involving regioselective heterocyclization of unsymmetrical thioureas (1 a–1 q). The synthesis was achieved at ambient temperature in good to excellent yields under catalyst free conditions. The molecular structures of 2‐ITZDs were elucidated by spectroscopic techniques such as FT‐IR, 1H‐NMR and 13C‐NMR. X‐ray structural data was used to establish the structure (2 o) unequivocally and to define the geometry of exo double bond. The in vitro anticancer activity of 2‐ITZDs (2 a–2 q) was investigated in several human cancer cell lines (A549, LNCap, PC‐3, MDA‐MB‐231, BxPC3, MIA PaCa2). All compounds showed cytotoxicity with IC50 values ranging from 6–23 μM in the tested cancer cell lines except MDA‐MB‐231. Compound 2 k (IC50=7 μM) and the homologous analog 2 q (IC50=6 μM) were found to be equipotent to 2 k and showed moderate cytotoxicity against human breast cell line (DA‐MB‐231). Furthermore, compound 2 k exhibited a medium permeability, enough metabolic stability and no significant inhibition of hERG channel. Compound 2 k inhibited cytochrome P450 activity below 50 % in 1 A2, 3 A4 and 2 C19, but not in 2 C9 and 2D6 at 10 μM. Structure‐activity relationships (SAR) provided useful insights towards this class of compounds and tiled a way to design novel analogues with increased potency.

Stereoselective synthesis of 1,2-annulated-C-Aryl glycosides from carbohydrate-derived terminally unsubstituted dienes and arynes: Application towards synthesis of sugar-fused- or branched- naphthalenes, and C-Aryl glycosides

Synthesis of 1,2-annulated-C-aryl glycosides has been achieved in a stereoselective manner through the Diels-Alder reaction between carbohydrate-derived terminally unsubstituted dienes and in situ generated arynes. In these reactions, formation of sugar-fused (or branched) naphthalenes was also observed and found to be temperature dependent and thus constituting one of the salient features of this work. The synthetic importance of 1,2-annulated-C-aryl glycosides has been explored by transforming them into densely oxygenated products by functionalizing the unsubstituted exo-double bond. Further, 1,2-annulated-C-aryl glycosides give rapid access to C-aryl glycosides in four steps.

Synthesis of Non-Conjugated Trienes via In Situ Hydrovinylation/Wittig Olefination of Unsaturated Phosphonium Salts

A cobalt-catalysed 1,4-hydrovinylation reaction is successfully applied in a sequential three-component transformation of unsaturated phosphonium bromides, 1,3-dienes, and aldehydes leading to non-conjugated products with a 1,4-diene subunit in good to excellent yields. The hydrovinylation provides regioselectively diene structures with one exo double bond whereas the third double bond can be introduced via an in situ Wittig or Horner–Wadsworth–Emmons olefination leading to 1,4,7-trienes suitable for further double bond functionalisations.

Poecillastrosides, Steroidal Saponins from the Mediterranean Deep-Sea Sponge Poecillastra compressa (Bowerbank, 1866).

The first chemical investigation of the Mediterranean deep-sea sponge Poecillastra compressa (Bowerbank, 1866) led to the identification of seven new steroidal saponins named poecillastrosides A–G (1–7). All saponins feature an oxidized methyl at C-18 into a primary alcohol or a carboxylic acid. While poecillastrosides A–D (1–4) all contain an exo double bond at C-24 of the side-chain and two osidic residues connected at O-2′, poecillastrosides E–G (5–7) are characterized by a cyclopropane on the side-chain and a connection at O-3′ between both sugar units. The chemical structures were elucidated through extensive spectroscopic analysis (High-Resolution Mass Spectrometry (HRESIMS), 1D and 2D NMR) and the absolute configurations of the sugar residues were assigned after acidic hydrolysis and cysteine derivatization followed by LC-HRMS analyses. Poecillastrosides D and E, bearing a carboxylic acid at C-18, were shown to exhibit antifungal activity against Aspergillus fumigatus.

Multidimensional mass spectrometry to characterize degradation products generated during MALDI of polystyrenes prepared by controlled radical polymerization techniques

An analytical workflow involving high resolution mass analysis, collision-induced dissociation and ion mobility was implemented to structurally characterize polymeric by-products detected in lieu of intact species when performing matrix-assisted laser desorption/ionization (MALDI) of polystyrenes with fragile end groups. Studied samples were prepared by atom transfer radical polymerization, reversible addition–fragmentation transfer polymerization and nitroxide-mediated polymerization. Spectral resolution enabled by orthogonal injection of MALDI ions into a reflectron time-of-flight mass analyzer allowed a thorough inventory of species, including some with the same nominal m/z value but different elemental composition. Individual end-group mass determination was achieved in MS/MS experiments, implementing an additional separative dimension based on ion mobility prior to CID to assist precursor ion selection in case of interferences. Besides validating commonly reported polystyrene chains terminated with either endo- or exo-double bond, this multidimensional approach permitted to show that initiating moiety could also be affected by the MALDI process. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 3388–3397

ChemInform Abstract: Utilization of Copper‐Catalyzed Carboarylation—Ring Closure for the Synthesis of New Oxazoline Derivatives.

Abstract1‐Aryl and 1‐alkylpropargylamides are transformed with arylmesityliodonium salts to deliver oxazoline derivatives with a fully substituted exo double bond in moderate to high yields.

Utilization of Copper-Catalyzed Carboarylation-Ring Closure for the Synthesis of New Oxazoline Derivatives.

A copper-catalyzed carboarylation-ring-closure strategy was used for the modular synthesis of oxazolines via the reaction of 1-aryl- and 1-alkylpropargylamides and diaryliodonium salts. The novel approach enables the efficient, modular synthesis of oxazoline derivatives bearing fully substituted exo double bonds.

A quantitative metric for conjugation in polyene hydrocarbons having a single classical structure.

A quantitative measure of the extent of conjugation is introduced. The number of Dewar resonance structures (DS) in a conjugated hydrocarbon quantitatively determines its extent of conjugation interaction. The greater the degree of conjugation the more stable is the conjugated hydrocarbon. The number of single bonds joining the exo-double bonds of a purely cross-conjugated hydrocarbon is equal to its number of Dewar resonance structures (DS). Polyene cross-conjugated hydrocarbons are minimally conjugated and possess only one classical structure with a succession of fixed single and exo-double bonds. There are three increasing levels of conjugation for systems with a single classical structure according to whether they are cross-conjugated, linear extended two-way conjugated, and ring-enhanced conjugated. Numerous analytical expressions have been derived. Our valence-bond (VB) approach involves studying the interrelationship of several well-known series of conjugated hydrocarbons having only a single classical structure, i.e., the number of Kekulé resonance structures is one (K = 1). This work provides a totally new perspective to the concept of conjugation.

Hobartine: a tetracyclic indole alkaloid extracted from Aristotelia chilensis (maqui).

The natural compound hobartine {systematic name: (1R)-3-[(1S,5S)-(4,4,8-trimethylbicyclo[3.3.1]non-7-en-2-yl)methyl]-2,3-dihydro-1H-indole}, C20H26N2, (I), is an indole alkaloid isolated from Aristotelia chilensis as part of a study of secondary metabolites from Chilean flora. The colourless compound has a tetracyclic structure closely related to the strongly coloured polymorphic structures discussed in Paz et al. [Acta Cryst. (2013), C69, 1509-1512] and Watson et al. [Acta Cryst. (1989), C45, 1322-1324]. The main differences reside in the absence of a keto group in (I) compared with the previous structures, as well as an endo double bond in (I) contrasting with the exo double bond found in the previous structures. The supramolecular structure of (I) in strongly related to the twofold screw axis, around which isolated chains build up, internally linked by an N-H···N hydrogen bond which is the only significant intermolecular interaction present in the structure.

ChemInform Abstract: Copper‐Catalyzed Oxidative Ring Closure and Carboarylation of 2‐Ethynylanilides.

AbstractA new copper‐catalyzed oxidative ring closure of ethynyl anilides with diaryliodonium salts is developed for the highly modular construction of benzoxazines bearing a fully substituted exo double bond.

Copper-Catalyzed Oxidative Ring Closure and Carboarylation of 2-Ethynylanilides

A new copper-catalyzed oxidative ring closure of ethynyl anilides with diaryliodonium salts was developed for the highly modular construction of benzoxazines bearing a fully substituted exo double bond. The oxidative transformation includes an unusual 6-exo-dig cyclization step with the formation of C-O and C-C bonds.

Cationic polymerization of isobutylene at room temperature

AbstractThis review highlights recent approaches toward polyisobutylene (PIB) by an energy efficient room temperature cationic polymerization. Special focus is laid on our own work using modified Lewis acids and nitrile‐ligated metal complexes associated with weakly coordinating anions. In both cases, suitable conditions have been found for efficient production of PIB characterized by medium to low molar masses and a high content of exo double bonds as end groups—the typical features of highly reactive PIB, an important commercial intermediate toward oil and gasoline additives. These and other approaches demonstrate that the cationic polymerization of isobutylene is still not fully explored, and new innovative catalyst systems can lead to surprising results of high commercial interest. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013

The role of solvent‐ligated metal(II) complexes incorporating (fluoroalkoxy)aluminates as weakly coordinating anions in isobutylene polymerization

AbstractNitrile‐ligated copper(II) and zinc(II) complexes comprising (fluoroalkoxy)aluminates as weakly coordinating anions (WCAs) have been synthesized and applied for the polymerization of isobutylene at room temperature (30°C). The polymers obtained are in the low and moderate molecular weight range and show characteristics of the highly reactive polyisobutylene. Results indicate that the fluoroalkoxy aluminate WCAs have even a higher tolerance toward water in IB polymerization than the earlier tested perfluoroborate WCAs. Studies showed that water plays an important role in the polymerization process, which indicates a polymerization mechanism similar to a proton‐initiated carbocation polymerization. The role of the WCAs and their importance for the room‐temperature polymerization process was re‐examined, and the effect of the addition of proton and electron donors including proton traps (2,6‐di‐tert‐butyl‐4‐methylpyridine or DTBP) was studied in detail. The polymerization reaction seems to be dominated by transfer reactions that lead to the high content of exo double bonds while propagation proceeds via conventional cationic polymerization. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013

Synthesis of highly reactive polyisobutylenes with BF3·cyclohexanol initiating system

The selective cationic polymerization of isobutylene (IB) initiated by a BF3·cyclohexanol (CL) complex was carried out from the mixed C4 fraction feed containing the 4C saturated and unsaturated hydrocarbons at −20°C. The effects of CL concentration, BF3 concentration, solvent for preparing BF3·CL complex and polymerization time on the chemical structure of end groups, number-average molecular weight (M n) and molecular weight distribution (MWD, M w/M n) of the resulting polymers were investigated. The experimental results indicate that the BF3·CL complex initiating system exhibited an extremely high selectivity toward the cationic polymerization of IB in the mixed C4 fraction feed and low molecular weight (M n = 900–3600) polyisobutylenes (PIBs) with large proportion of exo-double bond end groups were obtained. The exo-double bond content in PIB chain ends increased by increasing CL concentration or by decreasing solvent polarity in initiating system, BF3 concentration and polymerization time. The M n and MWD of the resulting PIBs were dependent on the concentrations of CL and BF3. Highly reactive PIBs with around 90 mol% of exo-double bonds were successfully synthesized by the selective polymerization of IB from the mixed C4 fraction feed, providing a potentially practical process for its simplicity and low costs.

Structure–activity relationships of larvicidal monoterpenes and derivatives against Aedes aegypti Linn

In the search for larvicidal compounds against Aedes aegypti L. (Diptera: Culicidae), a collection of monoterpenes were selected and evaluated. R- and S-limonene exhibited the highest larvicidal potency (LC50=27 and 30ppm, respectively), followed by γ-terpinene (LC50=56ppm) and RS-carvone (LC50=118ppm). Structural characteristics which may contribute to the understanding of the larvicidal activity of monoterpenes were empirically identified. The presence of heteroatoms in the basic hydrocarbon structure decreases larvicidal potency. Conjugated and exo double bonds appear to increase larvicidal potency. Replacement of double bonds by more reactive epoxides decreases the larvicidal potency. The presence of hydroxyls in the cyclic structure resulted in decreased potency, probably due to increased polarity indicanting that lipophilicity seems to play an important role in increasing the larvicidal potency in this set of compounds.