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.     

Oxygen replacement by fluorine in carbonyl derivatives of perfluoroaromatic compounds and isomerization of perfluoroindan-1,3-dione to perfluoro-3-methylenephthalide under the action of HF/SbF5

When acted upon by HF/SbF₅ at 95 °C, carbonyl groups of perfluorinated acetophenone (10), 3,4-dihydronaphthalen-1(2H)-one (8), 2,3-dihydronaphthalene-1,4-dione (9), benzocyclobutenone (6), benzocyclobutenedione (7) and indan-1-one (1) are converted into difluoromethylene groups to give the corresponding perfluoroaromatic products. Perfluoroindan-2-one (5), under the same conditions, is transformed to bis(perfluoroindan-2-yl) ether (21). On heating with HF/SbF₅, perfluoroindan-1,3-dione (2) isomerizes into perfluoro-3-methylenephthalide (4) at 95 °C, and gives 4,5,6,7-tetrafluoro-3-trifluoromethyl-phthalide (14) at 130 °C. Compound 4 in the absence of a solvent dimerizes giving perfluorodispiro[phthalide-3,1′-cyclobutane-2′,3″-phthalide] (18), and when heated with SbF₅ at 130 °C, it is converted into perfluoro-3-methylphthalide (3). When acted upon by HF/SbF₅ at 95 °C, perfluorinated benzoic acid (12) and phthalic anhydride (13) give the corresponding products with trifluoromethyl groups.     

Synthesis of a series of novel 2′,3′-dideoxy-6′,6′-difluoro-3′-thionucleosides

A series of novel 2′,3′-dideoxy-6′,6′-difluoro-3′-thionucleosides 1a-d, analogues of 3TC that has high biological activities against HIV and HBV, have been synthesized from the gem-difluorohomoallyl amine 7 in a straightforward fashion. Our synthesis featured the construction of thiofuranose skeleton through ring closure of key intermediates and installation of pyrimidine ring with amino group in compounds 13a,b.     

Synthesis of an ethidium nucleoside and its acyclic analog

The protected ethidium nucleosides 8-(3′,5′-di-O-benzoyl-2′-deoxy-d-ribofuranosyl)-3-acetamido-5-ethyl-6-phenyl-phenanthridinium (5), 8-(3′,5′-di-O-acetyl-2′-deoxy-d-ribofuranosyl)-3-acetamido-5-ethyl-6-phenyl-phenanthridinium (6), and the acyclic analog 8-[(3R)-1,3-dihydroxy-4-yl]-acetamido-3-amino-5-ethyl-6-phenyl-phenanthridinium (3) were prepared. Based on to their different stability, only the acyclic derivative 3 seems to be suitable for oligonucleotide synthesis. Furthermore, the acyclic ethidium nucleoside analog 3 exhibits comparable absorption and emission properties of the underivatized ethidium (1).     

Enantioselective synthesis of planar chiral azaferrocenes via chiral ligand-mediated ring- and lateral-lithiations

Lithiation of 1′,2′,3′,4′,5′-pentamethylazaferrocene (1) with sec-BuLi/(−)-sparteine (3) in Et₂O at −78°C followed by quenching with electrophiles gave the ring-substituted products 2 in 74-81% ee. On the other hand, lithiation of 1′,2,2′,3′,4′,5,5′-heptamethylazaferrocene (6) with sec-BuLi in the presence of S-valine-derived bis(oxazoline) 5 in Et₂O at −55°C and subsequent reaction with electrophiles afforded the laterally functionalized products 7 in excellent enantioselectivity (96-99% ee).     

Cationoid rearrangements in reactions of perfluoro-1-arylbenzocyclobutenes with antimony pentafluoride

In the presence of antimony pentafluoride at 130 °C, the four-membered ring of perfluoro-1-(2-ethylphenyl)benzocyclobutene (2) undergoes cleavage, forming perfluoro-2-ethyl-2′-methyldiphenylmethane (5). Compound 5 is converted, under the action of SbF₅ at 170 °C, to perfluoro-8,9-dimethyl-1,2,3,4-tetrahydrofluorene (8). Perfluoro-1-(4-ethylphenyl)benzocyclobutene (3) remains unchanged at 130 °C, whereas at 170 °C it gives a mixture of perfluorinated 4′-ethyl-2-methyldiphenylmethane (9), 6-ethyl-1,2,3,4-tetrahydroanthracene (11) and 2-ethyl-9,10-dihydroanthracene (12). When heated with SbF₅ at 170 °C, perfluoro-1-phenylbenzocyclobutene (1) remains unchanged. Solution of compounds 2, 3, 5 and 9 in SbF₅-SO₂ClF generated the perfluorinated 1-(2-ethylphenyl)-1-benzocyclobutenyl (29), 1-(4-ethylphenyl)-1-benzocyclobutenyl (30), 2-ethyl-2′-methyldiphenylmethyl (31) and 4′-ethyl-2-methyldiphenylmethyl (32) cations, respectively.     

Acyclic tertiary diamines and 1,4,7,10-tetraazacyclododecane with fluorine-containing β-diketones: Leading to low melting ionic adducts

N,N,N′,N′-Tetramethylmethanediamine (1a), N,N,N′,N′-tetramethylethanediamine (1b), N,N,N′,N′-tetramethyl-1,3-propanediamine (1c), and N,N,N′,N′-tetramethyl-1,6-hexanediamine (1d) were reacted at 25 °C with 1,1,1,5,5,5-hexafluoro-2,4-pentanedione (2a), 2,2-dimethyl-6,6,7,7,8,8,8-heptafluoro-3,5-octanedione (2b), 2-thenoyltrifluoroacetone (2c), and 4,4,4-trifluoro-1-(2-furyl)-1,3-butanedione (2d) to form the ionic adducts 3-18. 1,4,7,10-Tetraazacyclododecane (1e) reacted at 25 °C with β-diketones (2a-d) and 1,1,1-trifluoro-2,4-pentanedione (2e) to give ionic solids 19-23 in good yields. Some of the products are liquid at 25 °C and are thermally stable over long liquid ranges as determined by thermal gravimetric analyses. Single-crystal X-ray structure determinations show that compounds 9 and 21 crystallize in the monoclinic space groups P2(1)/c and P2(1)/n, respectively. All the new compounds were characterized by ¹H, ¹⁹F and ¹³C NMR, electrospray MS and/or elemental analyses.     

On the lithiation of oxazolinylaziridines

Lithiated N-sulfonyloxazolinylaziridines 6a and 7a, generated by deprotonation of the corresponding aziridines 6 and 7 with sec-BuLi/TMEDA at −98°C in THF, were found to be chemically and configurationally stable to be stereospecifically captured by electrophiles, while warming up to rt resulted in the formation of oxazolinylazirine 15. In contrast, lithiation of N-phenyloxazolinylaziridines 8 and 9 led to oxazolinylenamine 18. Tricyclic aziridines 10 and 11 resulted from an intramolecular addition of the aziridinyllithium 6a to the phenyl ring of the benzenesulfonyl group.     

Synthesis of 2,2′-bipyridyl derivatives using aza Diels-Alder methodology

Amidrazone 1 and the tricarbonyl derivatives 2a-c gave the triazines 3a-c, respectively, which reacted with 2,5-norbornadiene 4 in boiling ethanol yielding the corresponding novel 2,2′-bipyridines 5a-c in good yield. Triazine 6 gave the 2,2′-bipyridyl derivative 7 (65%) with compound 4 in 1,2-dichlorobenzene at 140°C.     

On the relative stereochemistry of atomaric acid and related compounds

The stereochemistry at C-3 of the known compounds atomaric acid 2a, 5′a-desmethyl-5′-acetylatomaric acid 4a, and stypoquinonic acid 5a is revised to 2, 4, and 5 on the basis of a careful study of 2D NOESY experiments and also from comparison of their ¹H and ¹³C chemical shifts with those of the related metabolites 6 and 7 isolated from Stypopodium zonale. Compound 7 is a novel unusually functionalized 1-keto-5′a-desmethyl atomaric acid derivative whose structure and stereochemistry were determined by spectroscopic means.     

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.     

The degradation of 4,5-dichloro-1,2,3-dithiazolium chloride in wet solvents

4,5-Dichloro-1,2,3-dithiazolium chloride 1 (Appel salt) reacts in wet DCM, THF or MeCN to give elemental sulfur, dithiazole-5-thione 4, dithiazol-5-one 5 and thiazol-5-one 6. Furthermore the reaction of 2-phenylthiazol-5(4H)-one 12 with Appel salt 1 at ca. 20 °C gives 4-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)-2-phenylthiazol-5(4H)-one 13 (26%) while at ca. 82 °C a new product 2,2′-diphenyl-4,4′-bithiazol-ylidene-5,5′-dione 14 (36%) is additionally isolated. Finally, 4,4′-bithiazolylidene-5,5′-dione 14 is prepared directly by treating 2-phenylthiazol-5(4H)-one 12 with N-chlorosuccinimide. All new compounds are fully characterised and rational mechanisms are proposed for the formation of all key compounds.     

Regiochemistry in the reductive opening of phthalan derivatives

The lithiation of phthalan derivatives 4, 9 and 12 with an excess of lithium in the presence of a catalytic amount of 4,4′-di-tert-butylbiphenyl (DTBB) in THF at −78 °C gives dianionic intermediates 5, 10 and 13, respectively, which by reaction with different electrophiles [H₂O, t-BuCHO, Me₂CO, (EtO)₂CO] at the same temperature, followed by hydrolysis, leads to regioselective functionalised naphthalenes 7, and biphenyls 11 and 14. The reductive opening takes place with high or total regioselectivity and can be explained considering the electron density in the dianion or in the radical anion, which are formed previous to the carbon-oxygen bond excision. The lithiation of the dihydrofurophthalan derivative 18 with the same reaction mixture but at higher temperature (0 °C) leads to intermediates 19 and 20, resulting from a single and a double reductive cleavage, respectively, which after addition of H₂O and benzaldehyde as electrophiles gives a mixture of compounds 21 and 22.     

Thermal decomposition of the tert-butyl perester of thymidine-5′-carboxylic acid. Formation and fate of the pseudo-C4′ radical

Thermal decomposition of the tert-butyl perester of thymidine-5′-carboxylic acid 1 carried out at 85 °C in different solvents affords the tert-butylacetal 4a, deriving from in cage decomposition, and pseudo C4′ radicals 2. Radicals 2 can be reduced to 5 by hydrogen atom abstraction from thiol (thiophenol or glutathione) or THF, or can be oxidized to cations 8 by dioxygen or perester 1 itself. Cations 8 are stereoselectively trapped by the nucleophilic solvent (tert-butanol, methanol, water) to give acetals 4a-c.     

Aigialomycins and related polyketide metabolites from the mangrove fungus Aigialus parvus BCC 5311

Reinvestigation of the secondary metabolites from the marine mangrove fungus Aigialus parvus BCC 5311 led to the isolation of six new nonaketide metabolites, aigialomycins F (4) and G (5a/5b), 7′,8′-dihydroaigialospirol (7), 4′-deoxy-7′,8′-dihydroaigialospirol (8), and rearranged macrolides 9 and 10, along with six previously described compounds, hypothemycin (1), aigialomycins A (2) and B (3), aigialospirol (6), 4-O-demethylhypothemycin (11), and aigialone (12). The structures of the new compounds were elucidated by analyses of the NMR spectroscopic and mass spectrometry data in combination with chemical means.     

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.     

Synthesis, structure, and catalytic activity of rhodium complexes with new chiral binaphthyl-based NHC-ligands

Three new chiral NHC-rhodium complexes have been prepared from the reactions between [Rh(COD)Cl]₂, NaOAc, KI, and dibenzimidazolium salts 3, 4 or 5, which are derived from (S)-2,2′-diamino-1,1′-binaphthyl. The steric and electronic effects of the ligand play an important role in the complex formation. For example, treatment of pyridine substituted dibenzimidazolium salts 3 or 4 with 0.5 equiv of [Rh(COD)Cl]₂ in the presence of NaOAc and KI in CH₃CN at 85 °C gives the chiral Rh(III) complexes 6 and 7, respectively. However, under similar reaction conditions, pyridine-N-oxide substituted dibenzimidazolium salt 5 affords a binuclear Rh(I) complex 8. All compounds have been characterized by various spectroscopic techniques, and elemental analyses. The solid-state structures of compounds 4-8 have been further confirmed by X-ray diffraction analyses. Rhodium complexes 6-8 show good catalytic activity for the asymmetric hydrosilylation of acetophenone with moderate ee values.     

Synthesis and properties of 4,9-methanoundecafulvenes and their transformation to 3-substituted 7,12-methanocycloundeca[4,5]furo[2,3-d]pyrimidine-2,4(1H,3H)-diones: photo-induced autorecycling oxidizing reaction toward amines

The synthesis and properties of 4,9-methanoundecafulvene [5-(4,9-methanocycloundeca-2′,4′,6′,8′,10′-pentaenylidene)pyrimidine-2,4,6(1,3,5H)-trione] derivatives 8a,b were studied. Their structural characteristics were investigated on the basis of the ¹H and ¹³C NMR and UV-vis spectra. The rotational barrier (ΔG^‡) around the exocyclic double bond of 8a was found to be 12.55 kcal mol⁻¹ by the variable temperature ¹H NMR measurement. The electrochemical properties of 8a,b were also studied by CV measurement. Furthermore, the transformation of 8a,b to 3-substituted 7,12-methanocycloundeca[4,5]furo[2,3-d]pyrimidine-2,4(1H,3H)-diones 16a,b was accomplished by oxidative cyclization using DDQ and subsequent ring-opening and ring-closure. The structural details and chemical properties of 16a,b were clarified. Reaction of 16a with deuteride afforded C13-adduct 19 as the single product, and thus, the methano-bridge controls the nucleophilic attack to prefer endo-selectivity. The photo-induced oxidation reaction of 16a and a vinylogous compound, 3-methylcyclohepta[4,5]furo[2,3-d]pyrimidine-2,4(3H)-dione 2a, toward some amines under aerobic conditions were carried out to give the corresponding imines (isolated by converting to the corresponding 2,4-dinitrophenylhydrazones) with the recycling number of 6.1-64.0 (for 16a) and 2.7-17.2 (for 2a), respectively.     

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.     

A novel class of organosoluble and light-colored fluorinated polyamides derived from 2,2-bis(4-amino-2-trifluoromethylphenoxy)biphenyl or 2,2-bis(4-amino-2-trifluoromethylphenoxy)-1,1-binaphthyl

Two series of novel fluorinated aromatic polyamides were prepared from 2,2^′-bis(4-amino-2-trifluoromethylphenoxy)biphenyl (2) and 2,2^′-bis(4-amino-2-trifluoromethylphenoxy)-1,1^′-binaphthyl (4) with various aromatic dicarboxylic acids using the phosphorylation polycondensation technique. The polyamides had inherent viscosities ranging from 0.43 to 0.62 dl/g and 0.36 to 0.74 dl/g, respectively. All the fluorinated polyamides were soluble in many polar organic solvents such as N,N-dimethylacetamide (DMAc), N-methyl-2-pyrrolidinone, and afforded transparent, light-colored, and flexible films upon casting from DMAc solvent. These polyamides showed glass-transition temperatures in the ranges of 190-240 °C (for the 6 series from diamine 2) and 247-255 °C (for the 7 series from diamine 4) by differential scanning calorimetry, softening temperatures in the ranges of 196-230 °C (6 series) and 241-291 °C (7 series) by thermomechanical analysis, and decomposition temperatures for 10% weight loss above 420 °C in both nitrogen and air atmospheres.