Substituent effects on the properties of photochromic diarylethenes

Photochromic symmetrical diarylethenes 1o-5o bearing different electron-donating or electron-withdrawing substitutents have been synthesized, and the structures of 1o, 2o, 4o, and 5o were determined by single-crystal X-ray diffraction analysis. Substitutent effects on their optoelectronic properties, including photochromism, fluorescence, and electrochemical properties were investigated in detail. The electron-withdrawing substituents can shift significantly the absorption maxima of the diarylethenes to a longer wavelength and increase their cyclization quantum yield, while the molar absorption coefficients increased with an increasing electron-donating ability. Diarylethenes 1, 2, and 4 show good photochromism both in solution and in the single crystalline phase; however, diarylethenes 5 show no photochromism in the crystalline phase because the distance between the reactive carbons become larger than 4.2 Å. Diarylethenes 1-3 exhibited good fluorescent switching upon alternating irradiation with UV and visible light, and their fluorescent conversions in the photostationary state were all larger than 80% in hexane. In addition, cyclic voltammetry tests showed that different electron-donating and electron-withdrawing substituents had a remarkable effect on the electrochemical behaviors of these diarylethenes.     

Syntheses and properties of new photochromic diarylethene derivatives having a pyrazole unit

New photochromic diarylethenes 1a, 2a and 3a bearing a pyrazole unit have been synthesized. Their properties, including photochromic reactivity, fluorescence and electrochemical properties were investigated. These compounds showed good photochromic properties, high cycloreversion quantum yield and relatively strong fluorescence. The cycloreversion quantum yields of 1a, 2a and 3a are 0.46, 0.53 and 0.57, respectively, which are larger than those of their cyclization quantum yields (0.43, 0.45 and 0.47, respectively). The oxidations of diarylethenes 1a, 2a and 3a were initiated at 0.73, 1.11 and 0.79 V, respectively. Moreover, the position of the methoxyl substituent had remarkable impacts on the above optical and electrochemical properties.     

Cobaloximes with mixed dioximes having C and S side chains: Synthesis, structure and reactivity

Ten mixed dioxime complexes RCo(L)(dmgH)Py [R = Cl, Me, Et, Bu, Benzyl] [L = dSPhgH (1-5) and dSEtgH (6-10)] have been synthesized and characterized by NMR. Formation of 1 and 6 is very fast and takes only 5 and 15 min in ethanol. Molecular oxygen insertion in 5 and 10 is monitored and forms mixture of products within 5 min. The crystal structure of 1, 4, 5, 6, 8 and 10 is reported. Benzyl ring is oriented over dmgH wing in both 5 and 10 and has a weak C-H…π interaction (3.33 Å and 3.22 Å) and this causes high upfield shift of the dmgH protons. Electrochemical study on 1, 4, 5, 6, 8 and 10 is also reported. Because of increased electron donation by SEt group, 6 is more difficult to reduce than 1.     

Rearrangement of the carbon skeleton in the intramolecular photoadduct of anthracene and benzene rings

The effectivity of optical switching between anthracene derivatives 3a,b and their intramolecular photocycloadducts 4a,b is impaired by traces of acid. The systematic treatment of 4a,b with an increasing excess of formic acid revealed that—apart from the normal enolether cleavage 4a,b→6a,b→7a,b—a cleavage with rearrangement of the carbon skeleton can occur: 5b→6b′. The driving force is a stability enhancement of the involved carbenium ions 5b→5b′. A further increased excess of formic acid leads finally to a competitive ether cleavage in the tetrahydrofuran ring 5b→8.     

Intramolecular carbolithiation promoted by a DTBB-catalysed chlorine-lithium exchange

The reaction of 6-chlorohex-1-ene 1 with lithium powder and a catalytic amount of 4,4′-di-tert-butylbiphenyl (DTBB, 5% molar) in THF at −78°C gives the corresponding organolithium intermediate 2, which by reaction with different electrophiles affords, after hydrolysis with diluted hydrochloric acid, the expected products 3. The same reaction performed at −30°C gives cyclopentyl derivatives 5, probably by cyclisation of the open-chain intermediate 2 to give the cyclic organolithium compound 4. When the double bond in the starting material contains an alkyl substituent, for instance compounds 6 and 9, the corresponding cyclisation is inhibited, so the corresponding acyclic products 8 and 11 are respectively, obtained. However, when the substituent at the same positions is a phenyl group, like in starting materials 12 and 15, the cyclised products 14 and 17 were respectively, isolated. In the case of the secondary starting chlorinated material 18, the reaction can be directed to both, the acyclic products 20 or the cyclic ones 22, working at −78 or −30°C, respectively, as it happens in the case of the unsubstituted chlorinated material 1. For the tertiary chloro derivative 23, only the cyclic compound 27 could be isolated at −30°C due to the great instability of the corresponding tertiary organolithium intermediate 24, which undergoes a proton abstraction even at −78°C. From allyl 2-chlorophenyl ether 28 or N,N-diallyl-2-chloroaniline 32, only the corresponding cyclic compounds 31 and 33, respectively, are isolated either at −78 or at −30°C. In all cases a carbanionic cyclisation, better than a radical one, is postulated to occur as mechanistic pathway.     

Chemoenzymatic resolution of epimeric cis 3-carboxycyclopentylglycine derivatives

Epimeric 3-carboxycyclopentylglycines (+)-10/(−)-10 and (+)-11/(−)-11 were efficiently prepared by the way of a sequence of Diels-Alder and retro-Claisen reactions. The synthesis incorporates a concise and inexpensive chemoenzymatic resolution of racemic compounds 4,5a, the N,O-protected derivatives of amino acids 10,11. Systematic screening with different enzymes and microorganisms was performed to select a very efficient catalyst for the separation of the racemic mixtures. The reaction conditions allowing deprotection of both ester and amino functions and to avoiding epimerization processes were studied. Enantiomers (i.e., (+)-10/(−)-10 and (+)-11/(−)-11) were obtained in high enantiopurity. The absolute configuration of all stereocenters was unequivocally assigned.     

The chemistry of zerumbone. Part 5: Structural transformation of the dimethylamine derivatives

Zerumbone (1) and its 6,7-epoxide (2) react with ammonia and dimethylamine regio- and stereospecifically, affording monoamines 3, 4, 7 and 8. All adducts have the same relative configuration at C2 and C3. The conjugate amination is thermodynamically controlled to arrive at a single diastereomer. At 15°C 7 reacts with cyanide to give aminonitrile 10 as the single product, while at 30°C, acyclic aminonitrile 11 is also formed. The reaction with 8 affords at 0°C bicyclic aminonitrile 12 of the asteriscane skeleton, while at 30°C or higher temperature, mixtures of 12 and tricyclic nitriles 13 and 13′ are obtained. Refluxing of 7, 8 and 10 in aqueous acetonitrile promotes scission of the zerumbone ring by retro-Mannich reaction to provide acyclic aldehydes 16-18, respectively. The dimethylamino group of 7, 8 and 10 is eliminated stereospecifically by Cope- and base-catalyzed eliminations to regenerate the zerumbone skeleton in the products 1, 2 and 21. Cope elimination of 12 results in a mixture of 13 and 13′ by deaminative transannular etherification.     

Synthesis and dynamics of atropisomeric (S)-N-(α-phenylethyl)benzamides

The synthesis of atropisomeric 2-substituted benzamides 2a-e, 3a-e, and 4a-e, and characterization by X-ray structure analysis of 2d, 2e, 3c, 3e, 4c, and 4e are reported. Dynamic ¹H NMR spectroscopic studies of benzamides 2b-d, 3b-d, and 4b-d indicate that only two of the four possible rotamers are present in solution, with population ratios ranging between 1.5:1 and 4.1:1. The measured free energy of activation to interconversion of the rotamers ranged from 12.4 to 18.9 kcal mol⁻¹. Benzamides ArCON[(S)-phenethyl]₂ (2e, 3e, and 4e), exhibited atropisomer ratios between 1.7:1 and 1:1, and free energies of interconversion of the rotamers ranged from 11.5 to 17.6 kcal mol⁻¹. The highest rotation barriers were observed for the ortho-nitro derivatives 2a-e. Molecular calculations at the semiempirical level (PM3MM) gave free energies of activation for benzamides 2e and 3e of 23.6 and 12.4 kcal mol⁻¹, respectively, which are comparable to the experimental values.     

A convenient synthesis of substituted 2,2′:6′,2″-terpyridines

The 2,2′:6′,2″-terpyridines 7a-c were prepared in good yield by reacting α-acetoxy-α-chloro-β-keto-esters 3a-c with bis-amidrazone 4 and 2,5-norbornadiene 6 in ethanol at reflux. Compounds 3a and 3b gave the 2,2′:6′,2″-terpyridines 9a and 9b, respectively, in moderate yield when treated with compound 4 and enamine 8.     

Heavy analogues of the 6π-electron anionic ring systems: Cyclopentadienide ion and cyclobutadiene dianion

The heavy analogues of the anionic 6π-electron systems, lithium 1,2-disila-3-germacyclopentadienide 2⁻ · [Li⁺(thf)], 1,2-disila-3,4-digerma- and 1,2,3,4-tetrasilacyclobutadiene dianions 7²⁻ · 2[K⁺(thf)₂] and 8²⁻ · 2[K⁺(thf)₂], were synthesized by the reduction of the neutral precursors 1, 3 and 4, respectively. 2⁻ · [Li⁺(thf)], the heavy analogue of the cyclopentadienide ion, is an aromatic compound, whereas 7²⁻ · 2[K⁺(thf)₂] and 8²⁻ · 2[K⁺(thf)₂], the heavy analogues of the cyclobutadiene dianion, are both non-aromatic.     

Total synthesis of eurypamides, marine cyclic-isodityrosines from the Palauan sponge Microciona eurypa

Total synthesis of eurypamides A, B, and D, 1, 2, and 4, has been successfully accomplished. The Tl(NO₃)₃ (TTN) oxidation of the halogenated bisphenols, 14a, 14b, 24, and 43, effected regio-controlled cyclization to provide the corresponding diaryl ethers, 15a, 15b, 25, and 46. This investigation revealed a structural revision of eurypamide A as to possess (2″S,3″R,4″S)-configuration (47), along with the spectral data of pure 2 and 4, which were previously characterized in a mixture.     

The enantioselective synthesis of poison-frog alkaloids (−)-203A, (−)-209B, (−)-231C, (−)-233D, and (−)-235B″

The enantioselective synthesis of indolizidines (−)-203A, (−)-209B, (−)-231C, (−)-233D, and (−)-235B″ has been achieved and the absolute stereochemistry of both indolizidines 203A and 233D was established as 5S,8R,9S. The relative stereochemistry of natural 231C was established by the present asymmetric synthesis.     

Synthesis and electrochemical properties of new cobalt and manganese phthalocyanine complexes tetra-substituted with 3,4-(methylendioxy)-phenoxy

The synthesis and electrochemical properties of new cobalt and manganese phthalocyanine complexes, tetra-substituted with 3,4-(methylendioxy)-phenoxy at the peripheral (complexes 3 and 5) and non-peripheral (complexes 4 and 6) positions, are reported. Complexes 3 and 4 showed Q-band absorption, in DMF, at 668 and 686 nm, respectively while Q-band due to complexes 5 and 6 appeared at 732 and 760 nm, respectively in CHCl₃. All the complexes showed well resolved redox processes attributed to both metal and ring based processes. Complexes 3 and 4 showed four redox processes, labeled I, II, III and IV. For complex 3, process I (Co^IPc⁻²/Co^IPc⁻³) was observed at −1.45 V, II (Co^IIPc⁻²/Co^IPc⁻²) at −0.38 V, III (Co^IIIPc⁻²/Co^IIPc⁻²) at +0.49 V and IV (Co^IIIPc⁻¹/Co^IIIPc⁻²) at +0.97 V versus Ag|AgCl. Similar processes were observed for complex 4 at −1.36 V, −0.27 V, +0.56 V, +1.03 V versus Ag|AgCl, respectively. Complexes 5 and 6 showed two redox processes (I and II). For complex 5, these processes appeared at −0.79 V (Mn^IIPc⁻²/Mn^IIPc⁻³, I) and −0.07 V versus Ag|AgCl (Mn^IIIPc⁻²/Mn^IIPc⁻², II), while for complex 6, they were observed at −0.86 V and −0.04 V versus Ag|AgCl. Spectroelectrochemistry was used to probe and confirm the origin of these processes.     

Synthesis, structural characterization, and initial electroluminescent properties of bis-cycloiridiated complexes of 2-(3,5-bis(trifluoromethyl)phenyl)-4-methylpyridine

A series of bis-cyclometalated Ir(III) complexes (8-10, 12, 15, 17, 19, 21, 23, 25, 28, 29 and 33) bearing two chromophoric N^∧C cyclometalated ligands derived from 2-(3,5-bis(trifluoromethyl)phenyl)-4-methylpyridine (1) and a third nonchromophoric ligand has been synthesized. A palladium-catalyzed cross-coupling reaction between 2-chloro-4-methylpyridine (2) and 3,5-bis(trifluoromethyl)phenylboronic acid (3) was used to prepare 2-(3,5-bis(trifluoromethyl)phenyl)-4-methylpyridine (1). Cyclometalation of (1) by IrCl₃ was carried out in (MeO)₃PO, with the formation of chloro-bridged dimer [N^∧C]₂Ir(μ-Cl)₂Ir[C^∧N]₂ (8). Reaction of (8) with lithium 2,4-pentanedionate, lithium 2,2,6,6-tetramethyl-heptane-3,5-dionate (13), dipivaloyltrimethylsilylphosphine (14), 2,2-dimethyl-6,6,7,7,8,8,8-heptafluoro-3,5-octadione (16), 1,1,1,3,3,3-hexafluoro-2-pyridin-2-yl-propan-2-ol (18), 1,1,1,3,3,3-hexafluoro-2-pyrazol-1-ylmethyl-propan-2-ol (20), 2-diphenylphosphanylethanol (22), and 1-diphenylphosphanylpropan-2-ol (24), afforded octahedral iridium complexes 9, 12, 15, 17, 19, 21, 23 and 25, respectively. Complex 10, which contains three different ligands (L₁ = N^∧C of 1; L₂ = N^∧C of 4,4′-dimethyl-[2,2′]bipyridinyl 4; L₃ = O^∧O of 2,4-pentanedione), and complex 11, which contains no cyclometalated ligands (L₁ = 4; L₂ = L₃ = Cl; L₄ = O^∧O of 2,4-pentanedione) were also isolated as minor products in a one-pot reaction between a 94:5 mixture of 1 and 4, IrCl₃ and lithium 2,4-pentanedionate. Reaction of 8 with diphenylphosphanylmethanol (27) in 1,2-dichloroethane unexpectedly led to complexes 28 and 29. The reactions of 8 with benzoylformic acid resulted in the formation of hydroxyl-bridged dimer [N^∧C]₂Ir(μ-OH)₂Ir[C^∧N]₂ (33). According to X-ray analyses, Ir-to-Ir distances in the crystal cell increase from 6.86 Å for 10 to 13.31 Å for 33. The angle theta, which represents the twisting of two cyclometalated C-Ir-N planes relative to each other, varies from 97.5° for 21 to 90.76 for complex 28. OLED devices were fabricated from several Ir complexes and preliminary results are discussed.     

Total synthesis of (+)-epiepoformin, (+)-epiepoxydon and (+)-bromoxone employing a useful chiral building block, ethyl (1R,2S)-5,5-ethylenedioxy-2-hydroxycyclohexanecarboxylate

Enantioselective total synthesis of (+)-epiepoformin 1, (+)-epiepoxydon 2 and (+)-bromoxone 3 using a chiral building block, ethyl (1R,2S)-5,5-ethylenedioxy-2-hydroxycyclo- hexanecarboxylate 6, is described. Since the synthesis afforded intermediates 18, 2 and 25, it accomplished a formal synthesis of (−)-theobroxide 19, (−)-phyllostine 22, (+)-herveynone 27 and (−)-asperpentyn 28. The usefulness of 6 for the synthesis of natural epoxycyclohexene derivatives was demonstrated.     

Synthesis of novel lariat azathia crown macrocycles containing two triazole rings and bis crown macrocycles containing four triazole rings

The 13-hydroxy macrocycles 7a-d were prepared in 40-50% yields by the condensation of 1,ω-bis(4-amino-1,2,4-triazol-3-ylsulfany)alkanes 2a-d with 1,3-bis(2-formyphenoxy)-2-propanol (9). Acylation of 7a-d with 2-chloroacetylchloride gave the corresponding esters 11a,b. Amination of 11a,b with different amines in acetone furnished exclusively the target lariat macrocycles 12a,b and 13 in 60-70% yields. Reaction of 2 equiv. of the macrocycles 11a,b with 1 equiv. of piperazine afforded the novel bis macrocyles 14a,b in 50-60% yields. Reduction of 7a-d with NaBH₄ afforded the corresponding 13-hydroxyazathia crown ethers 15a-d in 65-70% yields.     

Mg-promoted facile and selective intramolecular cyclization of aromatic δ-ketoesters

Treatment of various types of aromatic δ-ketoesters 2, 7, and 9 with Mg-turnings for Grignard reaction at −5 to 0 °C in N,N-dimethylformamide (DMF) containing trimethylsilyl chloride (TMSCl) brought about selective and reductive intramolecular cyclization to give the corresponding α-aryl-α-hydroxycyclopentanones 5, 8, and 10, respectively, in moderate to good yields. Similar reductive intramolecular cyclization of aromatic δ-ketodiesters 14, followed by acidic hydrolysis and decarboxylation easily gave the corresponding 2-aryl-2-cyclopenten-1-ones 15. The present facile coupling may be initiated through electron transfer from Mg metal to the aromatic carbonyl groups of 2, 7, 9, and 14 to generate the corresponding radical anions, followed by their intramolecular nucleophilic attack to the ester groups to give the corresponding five-membered ring compounds 5, 8, 10, and 15, respectively.     

Synthesis and characterization of half-sandwich Rh, Ir complexes containing mono-thiolate-ortho-carborane ligand

Two binuclear complexes [Cp^∗M(Cl)Carb^S]₂ (Cp^∗ = η⁵-C₅Me₅, M = Rh (1a), Carb^S = SC₂(H)B₁₀H₁₀, Ir (1b)) were synthesized by the reaction of LiCarb^S with the dimeric metal complexes [Cp^∗MCl(μ-Cl)]₂ (M = Rh, Ir). Four mononuclear complexes Cp^∗M(Cl)(L)Carb^S (L = BuⁿPPh₂, M = Rh (2a), Ir (2b); L = PPh₃, M = Rh (4a), Ir (4b)) were synthesized by reactions of 1a or 1b with L (L = BuⁿPPh₂ (2); PPh₃ (4)) in moderate yields, respectively. Complexes 3a, 3b, 5a, 5b were obtained by treatment of 2a, 2b, 4a, 4b with AgPF₆ in high yields, respectively. All of these compounds were fully characterized by IR, NMR, and elemental analysis, and the crystal structures of 1a, 1b, 2a, 2b, 4a, 4b were also confirmed by X-ray crystallography. Their structures showed 3a, 3b and 5a, 5b could be expected as good candidates for heterolytic dihydrogen activation. Preliminary experiments on the dihydrogen activation driven by these half-sandwich Rh, Ir complexes were done under mild conditions.     

Syntheses of glucose-containing E5564 analogues and their LPS-antagonistic activities

Lipid A analogues containing a glucose moiety on their non-reducing end were synthesized, and their LPS-antagonistic activities were measured. The inhibitory activities (IC₅₀) on LPS-induced TNFα production of these six compounds, 26, 33, 44β, 52β, 59, and 61, toward human whole blood cells were 0.49, 0.65, 0.51, 0.98, 0.46, and 1.11 nM, respectively. Inhibitory doses (ID₅₀) of compounds 26, 33, 44β, 59, and 61 on TNFα production induced by coinjection of galactosamine and LPS in C3H/HeN mice were measured. The ID₅₀ values of these compounds were 0.45, 0.96, <0.2, 1.08, and <0.2 mg/kg, respectively. Moreover, C3H/HeN mice preinjected with compounds 26, 33, and 44β were protected from lethality induced by coinjection of galactosamine and LPS. Out of eight mice preinjected with 1 mg/kg of compounds 26, 33, and 44β, five, eight and six mice were protected, respectively.     

Methylene-2-ethynylcyclopropanes: synthesis and biological activity of (Z)- and (E)-9-{[2-ethynyl-2-(hydroxymethyl)cyclopropylidene]methyl}adenine and -guanine

Synthesis of methylene-2-ethynylcyclopropane analogues of nucleosides 12a, 12b, 13a, and 13b is described. Ethyl methylenecyclopropane carboxylate 14 was hydroxymethylated to give alcohol 15, which was reduced to diol 16. Selective protection with tert-butyldimethylsilyl group gave derivative 17, which was oxidized to aldehyde 18. Wittig reaction with CBr₄ gave dibromoalkene 19. Elimination of both bromine atoms afforded methylene-2-ethynylcyclopropane 20. Bromoselenenylation using N-bromosuccinimide and diphenyldiselenide gave intermediate 21. Alkylation of adenine and 2-amino-6-chloropurine with 21 provided the Z,E-isomeric mixtures 22a and 22c. Oxidation afforded selenoxides 23a and 23c. Mild thermolysis furnished methylenecyclopropanes Z-24a, E-24a, and 24c. Deprotection and separation of Z,E-isomers gave adenine analogues 12a and 13a, and 2-amino-6-chloropurine intermediates 12c and 13c. Hydrolytic dechlorination of 12c and 13c afforded guanine analogues 12b and 13b. Adenine Z-isomer 12a inhibits replication of Epstein-Barr virus through its cytotoxicity. The E-isomer 13a is a substrate for adenosine deaminase.