Preparation and reactivity of macrocyclic dienynes

(1E,5E)-Cyclopentadeca-1,5-dien-3-yne (1c), which represents the first macrocyclic 1,5-dien-3-yne, can be obtained by thermal- or butyllithium-induced fragmentation of the corresponding 1,2,3-selenadiazole 8. The (E,E)-dienyne functionality causes a geometrical strain E_g, which enhances the reactivity in addition (1c→12,13) and cycloaddition (1c→10) reactions and lowers the isomerization barrier to the unstrained (E,Z)-configuration 1d (E_g = 0). A slow process 1c→1d occurs even at ambient temperatures within several weeks.     

Synthesis and photochemical properties of porphyrin-azobenzene triad

Porphyrin-azobenzene triad E-2, having ester spacers between the chromophores, was synthesized and its photochemical and thermal isomerization properties were investigated. Triad E-2 showed little electronic communication among the chromophores according to a comparison of the steady-state absorption and fluorescence spectra of E-2 and their model compounds. E-2 showed photochemical E-Z isomerization and subsequent thermal Z-to-E isomerization. The porphyrin chromophore in Z-2, obtained by photoisomerization, did not strongly affect the transient state of thermal Z-to-E isomerization of the azobenzene unit. The high E-isomer composition at the photostationary state indicates the occurrence of triplet energy transfer between porphyrin and azobenzene. E-2 forms a 1:1 complex with 4,4′-bipyridyl (Bipy). The stability constant for E-2 with Bipy was determined (log K = 4.20 mol⁻¹ dm³) by iterative least-squares fitting to a 1:1 binding model.     

Photochemistry of 3,6-bis(styryl)pyridazines in solution and in neat liquid crystalline phase—optical switching and imaging techniques

3,6-Bis(styryl)pyridazines 1a-f with 2-6 alkoxy groups show on irradiation in solution a stereoisomerization which leads to a photostationary state of (E,E)- and (E,Z)-isomer. Sensitizing and quenching experiments reveal that the (E,E)→(E,Z) route is a pure triplet process, whereas the (E,Z)→(E,E) route can have a minor singlet by-reaction.Hexyloxy or dodecyloxy chains on the terminal benzene rings convey the (E,E)-isomers of compounds 1a,b,d-f thermotropic liquid crystalline properties. In particular S_A, S_C, and S_F/I phases were studied with regard to their photochemical behavior. Depending on the system, photodegradation of the smectic phase to the isotropic melt (S→I) or photoinduction of the smectic phase (I→S) can be achieved by alteration of the (E,E)/(E,Z) ratio. These processes represent the basis for imaging techniques (writing and erasing of information).     

First total synthesis of fumaridine

The first total synthesis of the alkaloid fumaridine 1a is reported. The key step is the assemblage of the arylmethylene isoindolinone 2a (E) by Horner reaction between the phosphorylated isoindolinone 3a and the suitably substituted benzaldehyde 4. N-Lactam deprotection and concomitant E→Z isomerization complete the synthesis of the title compound.     

Positional isomerization of quinine and quinidine via rhodium on alumina catalysis: practical one-step synthesis of Δ-isoquinine and Δ-isoquinidine

The synthesis of Δ^3,10-isoquinine (5Z,5E) and Δ^3,10-isoquinidine (6Z,6E) was achieved in one-step through positional isomerization of the terminal alkene in the parent cinchona alkaloids using catalytic amounts of 5% Rh/Al₂O₃ and excess hydrochloric acid in refluxing 50% aqueous EtOH. The products were obtained in good yields as a mixture of E and Z geometric isomers and fully characterized using spectroscopic methods.     

Vinylidene carbonylation at a manganese-iron complex: A density functional study of mechanism

Treating the phenylvinyldene manganese complex Cp(CO)₂MnC¹C²HPh, 1, with [Fe(CO)₄] yields the binuclear μ-vinylidene complex Cp(CO)₂MnFe(μ-C¹C²HPh)(CO)₄, 2, that further isomerizes to the carbonylated product η⁴-[Cp(CO)₂MnC¹(CO)C²HPh]Fe(CO)₃, 3. In a computational study of the mechanism using a hybrid density functional method, we considered two stereoisomers for species 2 and 3 where the phenyl group at center C² is oriented in cis (E form) or trans (Z form) fashion to the Cp(CO)₂Mn unit. Isomers 2E and 2Z were calculated to be degenerate whereas the experimentally detected species 3E is 8 kcal/mol more stable than its isomer 3Z. The two-step pathway 1 → 2Z → 3E was calculated to be the lowest-energy route with the highest activation barrier at 12 kcal/mol. The activation energy of the alternative single-step pathway 1 → 3E is 19 kcal/mol. We rationalized the stabilization of the ground state of 3E and the transition states leading to or starting from isomer 2Z as conjugation effect between the Mn-CC metallaallene fragment and the co-planar phenyl ring.     

Thermal and photochemical isomerization of exocyclic 1,3-dienes: 1,1-diphenyl-3,4-bis(trimethylsilylmethylene)-1-silacyclopentane s-cis(E,E)

This paper describes the photochemical and the thermal isomerization of s-cis(E,E) 1,1-diphenly-3,4-bis(trimethylsilylmethylene)-1-silacyclopentane (1a). Under thermal conditions a 1,3-sigmatropic of the methylene hydrogen occurs, yielding the s-trans isomer (1b). The photochemical irradiation of (1a) at 300 nm for 1 h in deoxygenated benzene gives the corresponding s-cis(E,Z) isomer (1c) and then the s-cis(Z,Z) isomer (1d) after prolonged irradiation (3 h). There was no evidence for the formation of the corresponding cyclobutene resulting from the ring closure of the exocylic diene.     

Intramolecular allylboration of γ-(ω-formylalkoxy)allylboronates for syntheses of trans- or cis-2-(ethenyl)tetrahydropyran-3-ol and 2-(ethenyl)oxepan-3-ol

3-Alkoxy-1-alkynes 4 were hydroborated with pinacolborane (HBpin) to give 3-alkoxy-1-alkenylboronates 5. The latter gave (E)-3-alkoxyallylboronates (8: (E)-(MeO)₂CHCH₂(CH₂)_nCH₂OCHCHCH₂Bpin, n=1-3) when they were subjected to iridium-catalyzed isomerization of the double bond. The corresponding (Z)-isomers 10 were synthesized by nickel-catalyzed isomerization of 5. Both allylboronates underwent intramolecular allylboration leading to the formation of trans-2-(ethenyl)tetrahydropyran-3-ol or 2-(ethenyl)oxepan-3-ol from 8 and the corresponding cis-isomers from 10 in the presence of Yb(OTf)₃ (20 mol%) in aqueous acetonitrile at 90°C.     

A study of 1,5-hydrogen shift and cyclization reactions of an alkali isomerized methyl linolenoate

Heating a mixture formed by alkali isomerization of methyl linolenoate (1) produces a complex mixture with the bicyclic hexahydroindenoic esters 4β-(7-methoxycarbonylheptyl)-5α-methyl-2,3,3aα,4,5,7aαhexahydroindene (CL5) and 4β-ethyl-5α-(6-methoxycarbonylhexyl)-2,3,3aα,4,5,7aα-hexahydroindene (CL6) as main components. Similar isomerization reactions of three synthetic model compounds, methyl 9Z,13E,15Z-octadecatrienoate (2), 9Z,14E,16E-octadecatrienoate (4) and 9Z,11E,15Z-octadecatrienoate (5) corroborated the results obtained with alkali isomerized methyl linolenoate.     

The stereoselective synthesis of (E)-octafluoro-1,3,5-hexatriene and (3E,5E,7E)-dodecafluoro-1,3,5,7,9-decapentaene

(E)-(1,2-Difluoro-1,2-ethenediyl)bis[tributylstannane], 3, readily undergoes a Pd(PPh₃)₄/CuI-catalyzed cross-coupling reaction with iodotrifluoroethene to yield (E)-octafluoro-1,3,5-hexatriene, 4, in high isomeric purity. (1Z,3E,5Z)-(1,2,3,4,5,6-Hexafluoro-1,3,5-hexenetriyl)bis[tributylstannane], 7, was sequentially prepared from (1Z,3E,5Z)-(1,2,3,4,5,6-hexafluoro-1,3,5-hexenetriyl)bis[triethylsilane], 5, which was prepared via a Pd(PPh₃)₄/CuI-catalyzed cross-coupling reaction of 3 with (E)-1,2-difluoro-1-iodo-2-triethylsilylethene, 6. Pd(PPh₃)₄/CuI cross-coupling of 7 with iodotrifluoroethene gave (3E,5E,7E)-dodecafluoro-1,3,5,7,9-decapentaene, 8.     

Efficient synthesis of (Z)- and (E)-methyl 2-(methoxyimino)-2-phenylacetate

Direct oximation of 2-oxo-2-phenylacetate (3) gave the (Z)-methyl 2-(methoxyimino)-2-phenylacetate (1) in 71% yield, while the E oxime 2 was prepared from 3 in 65% yield via oxime isomerization of 2-(methoxyimino)-2-phenylacetic acid (5). Computational studies suggest that the isomerization of 5 is thermodynamically driven, while the direct oximation of ketoester 3 is kinetically controlled.     

π-Extended conjugate phenylacetylenes. Synthesis of 4-[(E) and (Z)-2-(4-ethenylphenyl)ethenyl]pyridine. Dimerization, quaternation and formation of charge-transfer complexes

The conjugate (E)- and (Z)-(4′-pyridylethenyl)-4-phenylethyne (E-4 and Z-4) has been satisfactorily prepared by two different routes: (a) by dehydrohalogenation of 4′-pyridylethenyl-4-phenyl-β-chloroethene; (b) by the Wittig reaction between p-(iodobenzyl)(triphenyl)phosphine ylide and 4-pyridinecarboxaldehyde, E/Z isomer separation, and cross-coupling with 2-methyl-but-3-yn-2-ol followed the propanone elimination. The Glaser oxidative dimerization of (Z)-4 yields (Z,Z)-1,4-di[(4′-pyridylethenyl)-4-phenyl]-buta-1,3-diyne in good yield, (Z,Z)-5. (E,E)-5 was obtained by phase transfer oxidative dimerisation of (E)-4 in presence of their N-methyl salt (E)-10. Mono- and di-N-methylated salts of conjugate (E,E)-5 and (Z,Z)-5, were obtained by quaternation with iodomethane. The (Z,Z)-5 di-N-methylated salt forms charge-transfer complexes with TCNE, TCNQ and TMPD.     

Stereoselective synthesis of 2-iodo-1-perfluoroalkyl-2(Z)-alkenes and E or Z-4-perfluoroalkylmethyl-4-en-2-ynol via Na2S2O4-promoted radical addition reaction of perfluoroalkyl iodides with allenes and the palladium-catalyzed kinetic resolution with Sonogashira coupling reaction

A Na₂S₂O₄-promoted radical addition reaction of perfluoroalkyl iodides with allenes has been studied in which a Z/E mixture of 2-iodo-1-perfluoroalkyl-2-alkenes 3 were afforded in 52-69% yields. A kinetic resolution using Sonogashira coupling reaction in MeCN using Et₂NH as the base was developed to synthesize the 2-iodo-1-perfluoroalkyl-2(Z)-alkenes (Z-3) and E-4-perfluoroalkylmethylalk-4-en-2-ynols (E-5) stereoselectively. A complete Sonogashira coupling procedure in Et₂NH at 40 °C was also developed affording a mixture of E and Z-4-perfluoroalkylmethyl-4-en-2-ynols (E-5 and Z-5), which may be easily separated by chromatography on silica gel.     

Alkoxy substituted (E,E)-3,6-bis(styryl)pyridazine—a photosensitive mesogen for liquid crystals

(E,E)-3,6-Bis(styryl)pyridazines (3a-t) bearing 2, 4 or 6 alkoxy chains were prepared by applying the Siegrist reaction of 3,6-dimethylpyridazine (13) and the corresponding azomethines 10a-t. The transversal dipole moment of these calamitic compounds effects an extremely high tendency for self-organization in thermotropic LC phases (N, S_A, S_B, S_C, S_E, S_I/F, and Cub). The conjugated core structure represents moreover a chromophore with a high photosensitivity for (E,E)?(E,Z) isomerization reactions: this property makes the compounds interesting for optical imaging and switching techniques.     

Alternative synthesis of cystothiazole A

Palladium-catalyzed methoxycarbonylation of (−)-(2R,3S)-1-tert-butyldimethylsiloxy-3-methyl-2-methoxypenta-4-yne 9 derived from (2R,3S)-epoxy butanoate 5 gave the acetylenic ester 10, which was treated with MeOH in the presence of Bu₃P to afford selectively (Z)-β-methoxy acrylate congener 11 in 86% yield. Treatment of (Z)-11 with 99.8% enrichment of CDCl₃ followed by consecutive desilylation and oxidation afforded the left-half aldehyde (+)-2. The overall yield (10 steps from 5; 23%) of (+)-2 via the present route was improved in comparison to that (10 steps from 5; 10%) of the previously reported route. By applying the modified Julia's coupling method, selectivity (E/Z=14:1) of the (E)-form (cystothiazole A 1) against the (Z)-form was improved in comparison to the Wittig method (E/Z=4:1 to 6.9:1).     

Non-degenerate 1,2-silyl shift in silyl substituted alkyltrimethylcyclopentadienes

The five new silanes C₅Me₃RSiMe_nCl_3 − n (n = 3, R = i-Pr (5); n = 2, R = i-Pr (6); n = 2, R = s-Bu (7); n = 2, R = cyclohexyl (8); and n = 3, R = t-Bu (9)) were synthesized by reaction of 1-alkyl-2,3,4-trimethylcyclopentadienyl lithium salts with appropriate chlorosilane and characterized by NMR, MS, and IR spectra. At elevated temperatures (250-360 K), all the silanes undergo a non-degenerate sigmatropic silyl rearrangement, which generates non-equivalent structures a and b. The presence of minor structure c was observed in compounds 5 and 7 only. The Diels-Alder cycloaddition of 5 with strong dienophiles tetracyanoethylene (TCNE), and dimethylacetylenedicarboxylate (DMAD) provides compounds 10 and 11, which confirmed isomers a and b, respectively. The free energy of activation of b → a isomerization for compounds 5-8 evaluated from variable temperature NMR spectra show only marginal influence of group R on the 1,2-silyl shift rate. Moreover, in compounds 5 and 7, the process b → a was found significantly faster than b → c process in the above-mentioned temperature range.     

Highly fluorinated C18 fatty acids: synthesis and interfacial properties

A fluorinated oleic acid 1-Z containing a perfluorooctyl group and its analogues (E-isomer 1-E, alkyne type 2 and saturated type 3) were synthesized in good yields. In these syntheses, it was found that a key compound 5 could be converted to each of 1-Z, 1-E and 2. Furthermore, equilibrium spreading pressures of their monolayers at the air-water interface were measured in order to demonstrate how the degree of unsaturation in the hydrophobic chain, the geometric isomerization, and the presence of F-atoms influence the monolayer stability. Irrespective of the structural alteration in the hydrophobic chains, the fluorinated fatty acids formed more stable monolayers with high spreading pressures as compared to their hydrocarbon counterparts.     

Rearrangements of tetrahydroimidazo[1,5-b]isoxazole-2,3-dicarboxylates to pyrrolo[1,2-e]imidazol-6-ols, precursors of 2,5-dihydro-1H-pyrrole derivatives

Isoxazolines 2 from the cycloaddition of imidazoline 3-oxides 1 with DMAD rearrange in the presence of methoxide to give cis-3-methoxy-7-(methoxycarbonyl)-2,7a-diaryl-5-oxo-2,3,5,7a-tetrahydro-1H-pyrrolo[1,2-e]imidazol-6-olates 3 with 100% de. The acidic hydrolysis of 3 led to kinetically controlled formation of methyl 1-formyl-4-hydroxy-5-oxo-2-phenyl-2-((arylamino)methyl)-2,5-dihydro-1H-pyrrole-3-carboxylates 6a-e. The intramolecular transformylations of the latter to the corresponding (E)- and (Z)-methyl 4-hydroxy-2-((N-(aryl)formamido)methyl)-5-oxo-2-phenyl-2,5-dihydro-1H-pyrrole-3-carboxylates 7a-e were shown to be substituent dependent (correlate with σ) and characterized by Hammett type equations. The effect of temperature was investigated and the ρ constants determined for the same reaction series at 50, 60 and 70 °C. The amide diastereomeric ratio [(E)-7]/[(Z)-7] is substituent dependent and can be described by the equation log[(E)]/[(Z)]_x=−ρσ_I+log[(E)]/[(Z)]_x=H.     

Synthesis of Methylenecyclopropane Analogues of Antiviral Nucleoside Phosphonates

Synthesis of methylenecyclopropane analogues of nucleoside phosphonates 6a, 6b, 7a and 7b is described. Cyclopropyl phosphonate 8 was transformed in four steps to methylenecyclopropane phosphonate 16. The latter intermediate was converted in seven steps to the key Z- and E-methylenecyclopropane alcohols 23 and 24 separated by chromatography. Selenoxide eliminations (15→16 and 22→23+24) were instrumental in the synthesis. The Z- and E-isomers 23 and 24 were transformed to bromides 25a and 25b, which were used for alkylation of adenine and 2-amino-6-chloropurine to give intermediates 26a, 26b, 26c and 26d. Acid hydrolysis provided the adenine and guanine analogues 6a, 6b, 7a and 7b. Phosphonates 6b and 7b are potent inhibitors of replication of Epstein-Barr virus (EBV).