[60]Fullerene adducts with 9-substituted anthracenes: mechanochemical preparation and retro Diels-Alder reaction

Three 9-substituted anthracene derivatives, that is, 9-hydroxymethylanthracene (2), 9-methoxymethylanthracene (3) and bis(9-anthrylmethyl) adipate (6), were chosen as the model compounds to evaluate the reactivity in their Diels-Alder reactions with [60]fullerene and in retro Diels-Alder reactions of the formed cycloadducts. Corresponding adducts 4, 5 and 7 were prepared in high yields under solvent-free conditions using high-speed vibration milling technique. In order to determine thermal stabilities of adducts 4, 5 and 7, their dissociations in the temperature range of 40-65 °C were investigated. Fitting the dissociation rates and temperatures to the Arrhenius equation gives the activation energies of 25.8, 21.8 and 24.9 kcal/mol for compounds 4, 5 and 7, respectively.     

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.     

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.     

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.     

Fluoride-induced intermolecular excimer formation of bispyrenyl thioureas linked by polyethylene glycol chains

New bispyrenyl thioureas linked by polyethylene glycol (PEG) chains, L1-L3, and methoxy benzene pyrene thiourea, L4, were synthesized. Upon binding with F⁻ in CHCl₃, L1-L3 exhibited strong excimer emission bands (I_E) and weak monomer emission bands (I_M), while L4 displayed the same intensity of both bands. However, little or no change was observed in fluorescence spectra of L1 upon adding OH⁻, AcO⁻, BzO⁻, H₂PO₄⁻, Cl⁻, Br⁻, and I⁻. Therefore, only F⁻ induced the pyrene excimer formation. Job’s plots showed 1/1 or 2/2 complexation of L1 with F⁻. Ratios of I_E/I_M of L1·F⁻ complex were dependent on the concentration of L1, implying that the dimerization of L1 proceeded via the intermolecular excimer formation. Among L1-L4, L1 possessed the highest binding constant and sensitivity toward F⁻ implying the importance of the linking PEG chain. L1 was demonstrated to be an excellent probe for F⁻ in CHCl₃ with the detection limit as low as 46.2 μg/L.     

Molecular structures and ab initio molecular orbital calculations of the optically active derivatives of 1-aminocyclopropane-1-carboxylic acid

The novel optically active derivatives of 2,2′-disubstituted-1-aminocyclopropane-1-carboxylic acid (−)-2 and (+)-3 were synthesised from the spiro-azlactone (+)-1. Oxidation of the diol moiety of (+)-3 gave by ring enlargement the racemic mixture of 2,3-dihydrofuran derivative (±)-6. This conversion is explained by stepwise rearrangement of the initially formed tetrasubstituted cyclopropanecarbaldehyde 4 through zwitterionic's reactive intermediate 5. The formation of (±)-6 is preferred energetically as established by ab initio calculations of the ground states and possible intermediates for that rearrangement. The crystal structure and absolute configuration of the compounds (+)-1, (−)-2, (+)-3 and (−)-7 were determined by single-crystal X-ray diffraction method. All four compounds possess Z-configuration of the cyclopropane ring. The dioxolane ring in the structures (+)-1 and (−)-2 adopts half-chair conformation, while the cyclopropane ring and geminally substituted groups in the structures (−)-2, (+)-3 and (−)-7 possess the anticlinal conformation. The molecules of the compound (+)-1 are connected by very weak intermolecular hydrogen bond of C-H?O type. In the compounds (−)-2, (+)-3 and (−)-7inter- and intramolecular hydrogen bonds of N-H?O type were observed. The spiro-compound (+)-1 exhibited a more pronounced inhibitory activity against the proliferation of murine leukemia and human T-lymphocytes cells than other type of tumor cell lines and normal human fibroblast cells.     

Nickel (II) complexes bearing 2-ethylcarboxylate-6-iminopyridyl ligands: synthesis, structures and their catalytic behavior for ethylene oligomerization and polymerization

A series of nickel (II) complexes (L)NiCl₂ (7-9) and (L)NiBr₂ (10-12) were prepared by the reactions of the corresponding 2-carboxylate-6-iminopyridine ligands 1-6 with NiCl₂ · 6H₂O or (DME)NiBr₂ (DME = 1,2-dimethoxyethane), respectively. All the complexes were characterized by IR spectroscopy and elemental analysis. Solid-state structures of 7, 8, 10, 11 and 12 were determined by X-ray diffraction. In the cases of 7, 8 and 10, the ligands chelate with the nickel centers in tridentate fashion in which the carbonyl oxygen atoms coordinate with the metal centers, while the carbonyl oxygen atoms are free from coordinating with the nickel centers in 11 and 12. Upon activation with methylaluminoxane (MAO), these complexes are active for ethylene oligomerization (up to 7.97 × 10⁵ g mol⁻¹ (Ni) h⁻¹ for 11 with 2 equivalents of PPh₃ as auxiliary ligand) and/or polymerization (1.37 × 10⁴ g mol⁻¹ (Ni) h⁻¹ for 9). The ethylene oligomerization activities of 7-12 were significantly improved in the presence of PPh₃ as auxiliary ligands. The effects of the coordination environment and reaction conditions on the ethylene catalytic behaviors have been discussed.     

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.     

Novel 2,7-substituted pyrene derivatives: syntheses, solid-state structures, and properties

A novel series of pyrene derivatives 3-6 functionalized with different aromatic substituents at 2,7-positions of the pyrene core have been readily synthesized by Suzuki coupling reactions. Single crystals suitable for X-ray crystallographic analysis of compounds 3-6 were all successfully obtained. The optical, electrochemical, and thermal properties of these newly synthesized compounds were thoroughly investigated and discussed. Theoretical calculation was adopted to study the geometric and electronic structure of compounds 3-6. Additionally, preliminary studies demonstrated that field-effect transistors using compound 3, 5, and 6 performed as p-type semiconductors, in which a field-effect mobility as high as 0.018 cm² V⁻¹ s⁻¹ and current on/off ratio of 10⁶ were achieved from compound 6.     

Enantioselective synthesis of axially chiral 1-(1-naphthyl)isoquinolines and 2-(1-naphthyl)pyridines through sulfoxide ligand coupling reactions

Racemic 1-(1′-isoquinolinyl)-2-naphthalenemethanol rac-12 was prepared through a ligand coupling reaction of racemic 1-(tert-butylsulfinyl)isoquinoline rac-7 with the 1-naphthyl Grignard reagent 10. Resolution of rac-12 was achieved through chromatographic separation of the Noe-lactol derivatives 14 and 15, providing (R)-(−)-12 of >99% ee and (S)-(+)-12 of 90% ee. The ligand coupling reaction of optically enriched sulfoxide (S)-(−)-7 (62% ee) with Grignard reagent 10 furnished rac-12, with the absence of stereoinduction resulting from competing rapid racemisation of the sulfoxide 7. Reaction of optically enriched (S)-(−)-7 with 2-methoxy-1-naphthylmagnesium bromide was also accompanied by racemisation of the sulfoxide 7, and furnished optically active (+)-1-(2′-methoxy-1′-naphthyl)isoquinoline (+)-3b in low enantiomeric purity (14% ee). The absolute configuration of (+)-3b was assigned as R using circular dichroism spectroscopy, correcting an earlier assignment based on the Bijvoet method, but in the absence of heavy atoms. Optically active 2-pyridyl sulfoxides were found not to undergo racemisation analogous to the 1-isoquinolinyl sulfoxide 7, with the ligand coupling reactions of (R)-(+)- and (S)-(−)-2-[(4′-methylphenyl)sulfinyl]-3-methylpyridines, (R)-(+)-17 and (S)-(−)-17, with 2-methoxy-1-naphthylmagnesium bromide providing (−)- and (+)-2-(2′-methoxy-1′-naphthyl)-3-methylpyridines, (−)-18 and (+)-18, in 53 and 60% ee, respectively. The free energy barriers to internal rotation in 3b and 18 have been determined, and the isoquinoline (R)-(−)-12 examined as a ligand in the enantioselectively catalysed addition of diethylzinc to benzaldehyde; (R)-(−)-12 was also converted to (R)-(−)-N,N-dimethyl-1-(1′-isoquinolinyl)-2-naphthalenemethanamine (R)-(−)-19, and this examined as a ligand in the enantioselective Pd-catalysed allylic substitution of 1,3-diphenylprop-2-enyl acetate with dimethyl malonate.     

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.     

Anion recognition through hydrogen bonding by adamantane-dipyrromethane receptors

Adamantane-dipyrromethane (AdD) receptors [di(pyrrole-2-yl)methyladamantane (1), 2,2-di(pyrrole-2-yl)adamantane (2), 1,3-bis[di(pyrrole-2-yl)methyl]adamantane (3), 2,2,6,6-tetra(pyrrole-2-yl)adamantane (4)] form complexes with F⁻, Cl⁻, Br⁻, AcO⁻, NO₃⁻, HSO₄⁻, and H₂PO₄⁻. The association constants of the complexes were determined by ¹H NMR titrations, whereas the geometries of complexes 1·F⁻ (2:1), 2·F⁻ (2:1), 2·Cl⁻ (2:1), 2·AcO⁻ (2:1), and 4·F⁻ (1:1) were determined by X-ray structural analysis. The most stable complexes are of 2:1 stoichiometry with F⁻ and AcO⁻. The stability constants are in accordance with the anion basicity and the ability of AdD receptors to place the hydrogen bonding donor groups in a tetrahedral fashion around anions. The binding energies of the complexes between receptors 1-4 and F⁻ anion are calculated using quantum chemical methods. The calculated results show that the solvent polarity is important for the complexation of fluoride ion with AdD receptors 1-4.     

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.     

Regioselective rearrangement of 7-azabicyclo[2.2.1]hept-2-aminyl radicals: first synthesis of 2,8-diazabicyclo[3.2.1]oct-2-enes and their conversion into 5-(2-aminoethyl)-2,3,4-trihydroxypyrrolidines, new inhibitors of α-mannosidases

Enantiomerically pure 2,8-diazabicyclo[3.2.1]oct-2-ene derivatives (+)-5 and (−)-5 have been obtained from 2-azido-3-tosyl-7-azabicyclo[2.2.1]heptanes (+)-1 and (−)-2 and their enantiomers, by ring expansion under radical conditions. Compounds (+)-5 and (−)-5 were transformed into hemiaminals 9 ((3S,4R,5R)- and 10 ((3R,4S,5S)-5-(2-aminoethyl)-2,3,4-trihydroxypyrrolidine) that are good inhibitors of α-mannosidases.     

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.     

Gold catalysis in stereoselective natural product synthesis: (+)-linalool oxide, (−)-isocyclocapitelline, and (−)-isochrysotricine

A stereoselective synthesis of the tetrahydrofuran-containing natural products (2S,5R)-(+)-linalool oxide (1), (−)-isocyclocapitelline (2), and (−)-isochrysotricine (3) is reported. Key steps are the copper-mediated S_N2′-substitution of propargyl oxiranes 7 and the gold-catalyzed cycloisomerization of dihydroxyallenes 8/17, resulting in a highly efficient center-to-axis-to-center chirality transfer. The enantioselective total synthesis of (−)-isocyclocapitelline (2) and (−)-isochrysotricine (3) allowed the elucidation of the absolute configuration of these β-carboline natural products.     

An efficient approach to 2-substituted N-tosylpiperdines: asymmetric synthesis of 2-(2-hydroxy substituted)piperidine alkaloids

We have developed an efficient and a general approach to chiral 2-substituted N-tosylpiperidines starting from chiral α-substituted-N-tosylaziridines. Using this approach, we have synthesized (+)-coniine. The synthesis of chiral N-tosyl-2-piperidinylethanol 15 and ent-15, was achieved from l- and d-aspartic acids, respectively in few steps. Piperidine 15 was converted into 2-(2-hydroxysubstituted)piperidines of type 2 in optically active form. By applying this strategy, asymmetric syntheses of halosaline (R,R)-2a, (+)- and (−)-sedamine 2b, (+)- and (−)-allosedamine 2c, (+)- and (−)-sedridine 2d, (+)- and (−)-allosedridine 2e, (+)-tetraponerine T-3 3a, T-4 3c, T-7 3b, and T-8 3d have been achieved in high yields. These stereoisomers can be interconverted via Mitsunobu inversion in excellent yields.     

Dopamine derivatives from the insect Polyrhachis dives as inhibitors of ROCK1/2 and stimulators of neural stem cell proliferation

Polyrhachis dives is consumed as an insect food in some regions of China. In this study, new dopamine derivatives, (+)-polyrhadopamine A (1a) and (−)-polyrhadopamine A (1b), (+)-polyrhadopamine B (2a) and (−)-polyrhadopamine B (2b), and polyrhadopamines C–E (3–5), were isolated from this species. The structures and stereochemistry of these substances were assigned by using spectroscopic and computational methods. Compounds 1a, 1b, 2a, and 2b are dimeric N-acetyldopamine derivatives, 3 is a dopamine analog containing an unusual sulfone group, and 4 and 5 possess a rare benzo[d]thiazole moiety. The functions of these substances as ROCK1/2 inhibitors, neural stem cell (NSCs) proliferation stimulators, immunosuppressive, and anti-inflammatory agents were determined.     

Design, synthesis, and characterization of the electrochemical, nonlinear optical properties, and theoretical studies of novel thienylpyrrole azo dyes bearing benzothiazole acceptor groups

Two series of related donor-acceptor conjugated heterocyclic azo dyes based on the thienylpyrrole system, functionalized with benzothiazol-2-yl (5-6) or benzothiazol-6-yl acceptor groups (7) through an NN bridge, have been synthesized by azo coupling using 1-alkyl(aryl)thienylpyrroles (1) and benzothiazolyl diazonium salts (2-4) as coupling components. Their optical (linear and first hyperpolarizability), electrochemical, and thermal properties have been examined. Optimized ground-state molecular geometries and estimates of the lowest energy single electron vertical excitation energies in dioxane solutions were obtained using density functional theory (DFT) at the B3LYP/6-31+G(d,p) level. Hyper-Rayleigh scattering (HRS) in dioxane solutions using a fundamental wavelength of 1064 nm was employed to evaluate their second-order nonlinear optical properties. Of these systems, the benzothiazol-2-yl-diazenes 5-6 exhibit the largest first hyperpolarizabilities (β=460-660×10⁻³⁰ esu, T convention) compared to benzothiazol-6-yl-diazenes 7 (β=360-485×10⁻³⁰ esu, T convention). Good to excellent thermal stabilities were also obtained for all azo dyes (235-317 °C). This multidisciplinary study showed that modulation of the optical and electronic properties can be achieved by introduction of the benzothiazole acceptor group in the thienylpyrrole system through position 2 or 6 of the benzothiazole heterocycle.     

Synthesis and electrochemical studies of ferrocene-dithiafulvalenes (Fc-DTF) and 1,1′-bis(dithiafulvalenyl)ferrocene (DTF-Fc-DTF). An approach towards new conducting organic materials

Novel π-conjugated donor compounds based on the strong electron-donating ferrocene moiety and dithiafulvalene donors exhibited increased electron donor ability. The ferrocenylketones 4a,b, 5, 8 and 9 were synthesized via described methods, and allowed to react with 2-dimethoxyphosphinyl-1,3-benzodithiole (13) in the presence of n-BuLi at −78°C in dry THF to afford the corresponding ferrocene-dithiafulvalenes 14a,b, 18, 19 and 1,1′-bis(benzo-1,3-dithiol-2-ylidene)ethyl]ferrocene (15). Electrochemical properties of these new donor compounds were studied using cyclic voltammetry (CV) and UV-Vis spectra. CV and absorption spectra of the new compounds were studied in comparison with ferrocene (6) and dibenzo-tetrathiafulvalene DB-TTF 3. Two-electron and three-electron redox behaviors were observed as two waves. The absorption spectra showed a red-shift with a slight increase in the absorption intensities.