Isomerization of E-α,β-epoxyamides to Z-α,β-epoxyamides and synthetic applications based on regio- and stereoselective oxirane ring openings

The regioselective opening reaction of 2,3-epoxyamides with various nucleophiles offers a variety of β-hydroxyamides with diverse synthetic utility depending on the introduced nucleophile. Due to the exclusive stereoselectivity in the formation of trans epoxyamides in reactions of aldehydes with stabilized sulfur ylides, we studied the isomerization of trans epoxyamides into the cis isomers with the objective of obtaining the corresponding syn opening products, which together with the anti isomers represent a variety of enantiomerically pure building blocks.     

Triazolopeptides: chirospecific synthesis and cis/trans prolyl ratios of structural isomers

As cis/trans prolyl isomerization plays a crucial role in various biological processes, peptide mimics capable of modifying the cis/trans Xaa-Pro ratio are of particular interest. A practical approach toward proline derived triazolopeptides employing [3+2] azide-alkyne cycloadditions as the key reaction step and the analysis of their cis/trans prolyl ratios are reported. Structural investigations indicated the adjustability of both the cis-percentage and the conformational stability toward intramolecular H-bonding effects.     

Structure‐Dependent cis/trans Isomerization of Tetraphenylethene Derivatives: Consequences for Aggregation‐Induced Emission

The isomerization and optical properties of the cis and trans isomers of tetraphenylethene (TPE) derivatives with aggregation‐induced emission (AIEgens) have been sparsely explored. We have now observed the tautomerization‐induced isomerization of a hydroxy‐substituted derivative, TPETH‐OH, under acidic but not under basic conditions. Replacing the proton of the hydroxy group in TPETH‐OH with an alkyl group leads to the formation of TPETH‐MAL, for which the pure cis and trans isomers were obtained and characterized by HPLC analysis and NMR spectroscopy. Importantly, cis‐TPETH‐MAL emits yellow fluorescence in DMSO at ?20 °C whereas trans‐TPETH‐MAL shows red fluorescence under the same conditions. Moreover, the geometry of cis‐ and trans‐TPETH‐MAL remains unchanged when they undergo thiol–ene reactions to form cis‐ and trans‐TPETH‐cRGD, respectively. Collectively, our findings improve our fundamental understanding of the cis/trans isomerization and photophysical properties of TPE derivatives, which will guide further AIEgen design for various applications.     

Trans-cis octahedral interconversion pathway in diorganotin compounds

Using structural data from bis(bidentate)diorganotin compounds in the Cambridge Structural Database a potential pathway for trans-cis interconversion is envisaged with nondissociative Sn-donor bonds and retaining metal coordination number 6. C-Sn-C bond angles in the range 180-145° correspond to skewed trapezoid bipyramidal geometry for 6- and 5-membered O,O′ chelates; geometries that resemble the transition state of the trans-cis pathway starts forming at about C-Sn-C 134°. cis-Diorganotins explored in this work have C-Sn-C bond angles in the range 102-110°; it is the statistically favored configuration for diphenyltins. The proposed trans-cis conversion pathway is deduced from a series of geometries associated with decreasing the C-Sn-C bond angle and shows 2 weakly (secondary) bound chelating atoms lengthening their bonds until near the transition state and later strengthening; they end up cis to each other and opposite to the organic groups. Conversely, the other 2 (primary) donors shorten their bonds until the transition state is reached and later lengthen; they end up trans to each other. The entire transformation from trans to cis configuration occurs with relative rotation of 3 bonds.     

PhP-PPh group bound to 1,8-positions of naphthalene: Preparation of cis isomer and synthesis of binuclear complex

A thermodynamically less stable cis isomer of 1,2-diphosphacycle was prepared from the corresponding trans isomer. Diphosphine, in which a PhP-PPh bond bridges the 1,8-positions of naphthalene, 1,2-diphenyl-1,2-dihydronaphtho[1,8-cd][1,2]diphosphole (1), was first prepared according to a previously reported method, and the trans isomer of 1 was irradiated in tetrahydrofuran with UV-vis light to reach equilibrium with cis-1 in a trans:cis ratio of 1:2. When a similar photochemical conversion was carried out using a saturated hexane solution of trans-1, cis-1 was precipitated in a good yield of 94%. The configuration of cis-1 was confirmed by X-ray analysis. Both cis- and trans-1 diphosphine ligands were used for the preparation of binuclear gold complexes. The crystal structure of (μ-cis-1)-[AuCl]₂ demonstrated that the two lone pairs of cis-1 are suitably directed for arrangement of the two gold centers in close proximity to each other. The two independent (μ-cis-1)-[AuCl]₂ molecules in the crystal were found to form a dimer through the multiple intermolecular interaction among the gold centers.     

Construction of macrocycle-based molecular stairs having pendant 4-aminopyridine, 4-dimethylaminopyridine and isonicotinonitrile groups

Self-assembly directed by dinuclear zinc(II) macrocyclic species with 4-aminopyridine, 4-dimethylaminopyridine and isonicotinonitrile produces four novel trans macrocycle-based complexes, namely three molecular stair elements and one one-dimensional (1D) polymeric stair. Controlled synthesis of the cis or trans isomers of 4-aminopyridine macrocyclic complexes (2a or 2b), where the same rigid macrocyclic platform and counterion are used, can be achieved merely by the substitution of a protonic solvent for a non-protonic solvent, and that is further verified by theoretical calculations. However, when the two hydrogen atoms of the amino group are replaced by methyl groups (i.e. 4-dimethylaminopyridine) in order to block the formation of effective hydrogen bonds, only the trans isomers (3a and 3b) can be obtained, either in protonic or non-protonic solvents. Moreover, when an isonicotinonitrile molecule, which has a stronger coordination ability and may act as a bidentate bridging ligand, is used, an infinite 1D macrocycle-based stair (4b) is generated via compensatory coordinative bonds as well as hydrogen bonding and face-to-face π–π stacking interactions.     

Synthesis and NMR spectra of the syn and anti isomers of substituted cyclobutanes—evidence for steric and spatial hyperconjugative interactions

The syn and anti isomers of cis,cis-tricyclo[5.3.0.0^2,6]dec-3-ene derivatives have been synthesized and their ¹H and ¹³C NMR spectra unequivocally analyzed. Both their structures and their ¹H and ¹³C NMR chemical shifts were calculated by DFT, the latter two calculations employing the GIAO perturbation method. Additionally, calculated NMR shielding values were partitioned into Lewis and non-Lewis contributions from the bonds and lone pairs involved in the molecules by accompanying NBO and NCS analyses. The differences between the syn and anti isomers were evaluated with respect to steric and spatial hyperconjugation interactions.     

RuO4-catalyzed oxidative polycyclization of the Cs-symmetric isoprenoid polyene digeranyl. An unexpected stereochemical outcome

The RuO₄-catalyzed oxidative polycyclization of digeranyl, a C_s-symmetric tetraene possessing a repetitive 1,5-diene structural motif, has been studied. The required substrate has been synthesized by Ti(III)-mediated tail-to-tail homocoupling of geranyl bromide. The process afforded two hitherto unknown isomeric tris-tetrahydrofuran products possessing unexpected all-threo cis-trans-cis and cis-trans-trans relative configuration. The new stereochemical outcome is explained based on previously formulated chelation or steric control models on the basis of structural differences between digeranyl and previously studied isoprenoid polyenes farnesyl acetate, geranylgeranyl acetate and squalene.     

Catalytic activity of Mn(III) and Fe(III) complexes of meso-tetra(n-propyl)porphyrin in oxidation of olefins: Meso-alkyl substituent in comparison with the alkenyl and aryl ones

Catalytic activity of Mn(III) and Fe(III) complexes of meso-tetra(n-propyl)porphyrin, MnT(n-Pr)P(X) and FeT(n-Pr)P(X) (X = Cl, SCN, OAc) in oxidation of olefins with tetra-n-butylammonium periodate at room temperature has been studied. The influence of different parameters including the molar ratio of catalyst to imidazole, type of counter ion (X) and oxidative stability of metalloporphyrins on the efficiency of the catalysts was investigated. The results of competitive oxidation of cis- and trans-stilbene suggest the presence of a high-valent Mn-oxo as the predominant oxidant species in equilibrium with a six coordinate complex, MnT(n-Pr)P(ImH)(IO₄) in the case of MnT(n-Pr)P(OAc). An unusual preference for trans-stilbene over cis-stilbene was observed in the reaction catalyzed by FeT(n-Pr)P(OAc). Control reaction indicated a significant cis- to trans-isomerization (81%) in oxidation of cis-stilbene catalyzed by FeT(n-Pr)P(OAc) which may explain the observed unusual cis to trans-stilbene oxide ratio. While oxidation of cyclooctene and styrene led to the exclusive formation of the corresponding epoxides, oxidation of cyclohexene gave 2-cyclohexe-1-ol and cyclohexene oxide as the products. However, the results of this study clearly demonstrate the key role played by the group substituted at the meso positions of metalloporphyrins on their catalytic activity, apart from the electron-donating or electron-withdrawing properties of the substituents.     

First separation and characterization of cis and trans 1,2-bisaryloxy perfluorocyclobutanes

4-Bromotrifluorovinyloxybenzene (4-Br-TFVE) undergoes cyclodimerization upon heating at 150 °C affording cis and trans isomers of 1,2-bis(4-bromophenoxy)hexafluorocylcobutane. Stereoisomers were separated by selective crystallization, confirmed by single crystal X-ray, and further characterized by NMR. Remarkable difference in the solid state structures include aryl to aryl dihedral angles of 12° for the trans isomer and 88° for the cis isomer. Polymers containing roughly equal amounts of cis and trans fused perfluorocyclobutyl (PFCB) rings should be expected to have low crystallinity due to the marked difference in the two unit cells as is observed.     

Cyclic oligomers in the cationic polymerization of cis- and trans-2,3-dimethylthiirane

Under the influence of triethyloxonium tetrafluoroborate in methylene chloride, cis- and trans-2,3-dimethylthiirane are transformed to their corresponding polymers almost instantaneously (at temperatures between 0 and 20 °) but within a few hours these polymers completely degrade to form a mixture of low molecular weight substances. The cis-monomer leads to a mixture of cyclic tetramer, cis-butene and two geometric isomers of 3,4,6,7-tetramethyl-1,2,5-trithiepane. By ¹H-NMR it was shown that these two isomers are the trans-cis-trans and the trans-trans-trans forms. The trans-monomer leads to a mixture of trans-butene and 3,4,6,7-tetramethyl-1,2,5-trithiepane which is present as a mixture of the cis-cis-cis and the cis-trans-cis isomers. In both cases, the butene and the trithiepanes were formed in equimolar quantities. The formation of these oligomers is explained by assuming that polymerization occurs via an SN2 propagation reaction between the three-membered cyclic sulphonium ion (the active species) and monomer, followed by a degradation reaction occurring via a back-biting mechanism.     

Isolation of the retinal isomers from the isomerization of all-trans-retinal by flash countercurrent chromatography

The isolation of the retinal isomers from all-trans-retinal was performed by flash countercurrent chromatography. In each separation, isomerization reaction solution of 200 mg all-trans-retinal could be loaded on a 1200 mL of high-speed countercurrent chromatographic column with 5 mm bore, eluted by a mobile phase flow rate of 25 mL/min, resulting in 63 mg of 11-cis-retinal, 24 mg of 13-cis-retinal and 26 mg of 9-cis-retinal with purities more than 95%. n-Hexane–acetonitrile (3:1) was used as the solvent system which possesses the advantages of simplicity, re-use of the solvent and multiple injections. This method could be used to prepare 13-cis-retinal, 11-cis-retinal and 9-cis-retinal for the photoisomerization investigation, such as the effect of 11-cis-retinal in the visual system.     

Biocatalytic preparation of enantioenriched 3,4-dihydroxypiperidines and theoretical study of Candida antarctica lipase B enantioselectivity

Enzymatic acetylations of N-substituted cis- and trans-3,4-dihydroxypiperidine and hydrolysis of their diacetylated derivatives have been studied. High enantioselectivities are obtained with Pseudomonas cepacia lipase and Candida antarctica lipase B for the hydrolysis of the trans-derivative, while the cis-derivatives are not adequate substrates in the same biocatalytic conditions. The enantiopreference of these processes can be rationalized by means of a molecular modelling study.     

Mechanochemical-induced cis-to-trans isomerization of poly(2-ethynyl-3-n-octylthiophene) prepared with a Rh complex catalyst

Highly stereoregular polymerization of 2-ethynyl-3-n-octylthiophene was successfully performed with a [Rh(norbornadiene)Cl]₂ catalyst to produce the corresponding polymers in fairly high yields by using triethylamine or a mixture of it with other solvents as the polymerization solvent. We found that the obtained polymer using CHCl₃ was a mixture of cis-transoid form, ca. 68% and trans-transoid form, ca. 32% unlike our previous conjecture. Further, we found that the cis-to-trans isomerization can be also induced when the pristine predominant cis polymer was subjected to mechanochemical grinding (MCG) treatment at 77 K using a mortar filled with liquid nitrogen to decrease the cis content from ca. 68% to ca. 7%. The polymers obtained before and after the MCG treatment were characterized in detail using ¹H NMR, laser Raman, solution UV-vis, diffuse reflective UV-vis, and ESR methods in order to determine the geometry of the main-chain CC bonds in the polymer. The data showed that the polymer obtained by the treatment has a fairly distorted trans conjugation length, i.e., bent trans structure in which less mobile unpaired electrons generated by the rotational scission of the original cis CC bonds are stabilized.     

Ultrasound-assisted convenient synthesis of hypolipidemic active natural methoxylated (E)-arylalkenes and arylalkanones

An ultrasound-assisted convenient method was developed for the conversion of toxic methoxylated cis-isomer of arylalkenes into its hypolipidemic active trans-isomer. Treatment of cis-isomer or mixture of all three isomers (1a-1j) with ammonium formate and 10% Pd/C gave arylalkanes (2a-2j), which upon oxidation with DDQ in anhydrous dioxane containing a little amount of silica gel, provided (E)-arylalkenes (3a-3g) in 42-72% yield depending upon the substituents attached at the aryl ring. The same method, upon addition of a few drops of water, provided hypolipidemic active arylalkanones (3h-3j) in 59-65% yield.     

Solvent dependent photo-isomerization of 4-dimethylaminoazobenzene carboxylic acid

We have observed reversible trans–cis photo-isomerization behaviors of 4-dimethylaminoazobenzene carboxylic acid (4DAzC) in ethyl acetate by alternating irradiations at 370 and 430 nm. The photo-isomerization from trans- to cis-isomer was found to be strongly solvent dependent and not to occur efficiently in water and ethanol. Also photo-isomerization from cis- to trans-isomer was occurred upon 370 nm illumination or via thermal relaxation. The activation energy for the thermal isomerization from cis to trans-isomer was estimated to be 49.2 kJ/mol in ethyl acetate from the temperature-dependent kinetic absorption measurements.     

The mass spectra of carboxylic acids·IV: Carboxyl-carboxyl interaction in some cycloalkane 1,2 dicarboxylic acids and its relationship with molecular geometry

The interaction of the carboxyl groups in the fragmentation of the molecular ions of trans cyclohexane-1,2-dicarboxylic acid and cis cyclobutane-1,2-dicarboxylic acid serves to distinguish these acids from their cis and trans isomers respectively. This ‘ortho effect’ can be related to the geometrical arrangement of the carboxyl groups in the ground-state molecules.     

Geometrical preferences of the crotyl anion,radical and cation

ab initio MO calculations have been performed on the cis and trans isomers of the crotyl cation, free radical and anion in each of two orientations of the Me rotor about the allylic framework. In agreement with available experimental data, both the crotyl cation and free radical prefer trans skeletal geometries. On the other hand, the cis isomer of the crotyl anion is found to be more stable than the trans, the same preference as has been noted for alkali metal allyl organometallics in solution, but opposite to that recently reported for the free (gas phase) anion. The Me groups are predicted to eclipse the partial double bond for the trans isomers of all three systems and for the cis cation. These results are rationalized with the aid of perturbation MO theory.     

Synthesis of N-heterocyclic diols by diastereoselective pinacol coupling reactions

A series of 5-8 membered N-heterocyclic diols have been prepared from acyclic dicarbonyls via diastereoselective pinacol reactions whereby cis- or trans-diol stereoselectivity is controlled by the choice of low-valent metal reagent used.     

Occurrence of oleic and 18:1 methyl-branched acyl chains in lipids of Rhodobacter sphaeroides 2.4.1

The fatty acids (FAs) composition of lipids extracted from Rhodobacter sphaeroides 2.4.1 was investigated by gas chromatography–mass spectrometry (GC–MS) analysis of the corresponding FA methyl esters (FAMEs), obtained through trans-esterification of the original lipid species. A GC stationary phase based on a highly polar ionic liquid (IL) was selected, aimed to enhance the separation of isomeric FAMEs with particular emphasis on positional and geometrical isomers of monounsaturated 16:1 and 18:1 fatty acyl chains. The occurrence of 18:1 cis-Δ⁹ (oleic) acid, a positional isomer of the well-known and most predominant 18:1 cis-Δ¹¹ (cis-vaccenic) acid, has been demonstrated here for the first time. Furthermore a methyl branched 18:1 FA was also identified and its structure tentatively assigned as 11-methyl-Δ¹²-octadecenoic acid (most likely as trans isomer). The unprecedented observation about 18:1 cis-Δ⁹ FA occurrence in R. sphaeroides 2.4.1 is, even indirectly, supported by a biosynthetic pathway postulated with the aid of the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The concurrent presence of 16:1 cis-Δ⁷ and 18:1 cis-Δ⁹ FAs suggested the existence of parallel and/or complementary processes to those invoked for the formation of most common 16:1 cis-Δ⁹ and 18:1 cis-Δ¹¹ FAs. A further route was hypothesized for the trans FAs biosynthesis in wild-type cells of R. sphaeroides.