Stabilization of ortho-quinone methides by a bis(sulfonium ylide) derived from 2,5-dihydroxy-[1,4]benzoquinone

The zwitterionic intermediates (2a) in the oxidation of ortho-alkylphenols (1) and bis(sulfonium ylide) 3 form reasonably stable 2:1-complexes (4), in which the ortho-quinone methide (oQM) moieties are not present in quinoid form with the exocyclic in-plane methylene group, but as zwitterionic, aromatic conformer having an out-of-plane exocyclic methylene group. The complex 7 derived from the α-tocopherol model compound PMC (5) was comprehensively characterized. As exemplarily demonstrated, the adducts can be advantageously employed in organic synthesis as ‘stabilized oQMs’.     

Preparation, crystal structure, and spectroscopic, chemical, and electrochemical properties of (2E,4E)-4-[4-(dimethylamino)phenyl]-1-(3-guaiazulenyl)-1,3-butadiene compared with those of (E)-2-[4-(dimethylamino)phenyl]-1-(3-guaiazulenyl)ethylene

Wittig reaction of 3-[4-(dimethylamino)phenyl]propanal (5) with (3-guaiazulenylmethyl)triphenylphosphonium bromide (4) in ethanol containing NaOEt at 25 °C for 24 h under argon gives the title (2E,4E)-1,3-butadiene derivative 6E in 19% isolated yield. Spectroscopic properties, crystal structure, and electrochemical behavior of the obtained new extended π-electron system 6E, compared with those of the previously reported (E)-2-[4-(dimethylamino)phenyl]-1-(3-guaiazulenyl)ethylene (12), are documented. Furthermore, reaction of 6E with 1,1,2,2-tetracyanoethylene (TCNE) in benzene at 25 °C for 24 h under argon affords a new Diels-Alder adduct 8 in 59% isolated yield. Along with spectroscopic properties of the [π4+π2] cycloaddition product 8, the crystal structure, possessing a cis-3,6-substituted 1,1,2,2-tetracyano-4-cyclohexene unit, is shown. Moreover, reaction of 6E with (E)-1,2-dicyanoethylene (DCNE) under the same reaction conditions as the above gives no product; however, this reaction in p-xylene at reflux temperature (138 °C) for four days under argon affords a new Diels-Alder adduct 9 in 54% isolated yield. Although reaction of 6E with DCNE in toluene at reflux temperature (110 °C) for four days under argon provides 9 very slightly, reaction of 6E with dimethyl acetylenedicarboxylate (DMAD) in toluene at reflux temperature for two days under argon yields a new Diels-Alder adduct 10, in 58% isolated yield, which upon oxidation with MnO₂ in CH₂Cl₂ at 25 °C for 1 h gives 11, converting a (CH₃)₂N-4″ into CH₃NH-4″ group, in 37% isolated yield. The crystal structure of 11 supports the molecular structure 10 possessing a partial structure cis-3,6-substituted 1,2-dimethoxycarbonyl-1,4-cyclohexadiene. The title basic studies on the above are reported in detail.     

New α-substituted alkylbenzene- and dialkylbenzene-1,2-diphosphonates: side-chain metalation of tetraethyl 4-methyl- and 4,5-dimethylbenzene-1,2-diphosphonates

Carbocyclic 1,2-diphosphonates (1a, 1b) are prepared by the Diels-Alder reaction of classical donor alka-1,3-dienes (isoprene and 2,3-dimethyl-1,3-butadiene) with tetraethyl acetylene bisphosphonate. Their aromatization by the KMnO₄-Al₂O₃ system affords 4-methyl and 4,5-dimethylbenzene-1,2-diphosphonates (2a, 2b), used as precursor for the generation of benzyl-type carbanions (3a, 3b) by lithiation with lithium isopropylamide in THF at −80 °C. The carbanions react with electrophilic reagents (chlorotrimethylsilane, p-fluorobenzaldehyde, and ethyl trifluoroacetate) in situ to form corresponding α-substituted monoalkyl- and dialkylbenzenediphosphonates in good yields.     

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.     

An efficient catalyst for the synthesis of ortho-substituted biaryls by the Suzuki cross-coupling: Triphenylphosphine adduct of cyclopalladated ferrocenylimine

The air and moisture stable triphenylphosphine adduct of cyclopalladated ferrocenylimine 2 has been successfully used in palladium-catalyzed Suzuki cross-coupling for the synthesis of ortho-substituted biaryls in air. In the presence of 0.05 mol% of 2 as catalyst and 3 equivalent of CsF as base in dioxane at 100 °C, ortho-substituted biaryls were synthesized with moderate to high yields in the reactions of 2-methoxy-1-naphthylboronic acid with aryl halides, and 14 new ortho-substituted biaryls were obtained and characterized.     

Novel intramolecular cyclization of 2-(buta-1,3-dienyl)-3-methylpyrazines and 3-(buta-1,3-dienyl)-4-methyl-1,2,5-oxadiazoles into 5H-cycloheptapyrazines and 4H-cyclohepta-1,2,5-oxadiazoles

2-(Buta-1,3-dienyl)-3-methylpyrazines (5) and 3-(buta-1,3-dienyl)-4-methyl-1,2,5-oxadiazoles (10) were synthesized starting from base-induced reaction of 2,3-dimethylpyrazine or 3,4-dimethyl-1,2,5-oxadiazole with α,β-unsaturated carbonyls. The thus obtained heteroaromatics bearing a butadienyl moiety and a methyl at the adjacent position underwent intramolecular cyclization by the action of LDA to give the corresponding heteroaromatics fused with a seven-membered ring [7 (8)] and [11 (12)] in moderate to high yields.     

Syntheses and structures of iron carbonyl complexes derived from N-(5-methyl-2-thienylmethylidene)-2-thiolethylamine and N-(6-methyl-2-pyridylmethylidene)-2-thiolethylamine

The reaction of N-(5-methyl-2-thienylmethylidene)-2-thiolethylamine (1) with Fe₂(CO)₉ in refluxing acetonitrile yielded di-(μ₃-thia)nonacarbonyltriiron (2), μ-[N-(5-methyl-2-thienylmethyl)-η¹:η¹(N);η¹:η¹(S)-2-thiolatoethylamido]hexacarbonyldiiron (3), and N-(5-methyl-2-thienylmethylidene)amine (4). If the reaction was carried out at 45 °C, di-μ-[N-(5-methyl-2-thienylmethylidene)-η¹(N);η¹(S)-2-thiolethylamino]-μ-carbonyl-tetracarbonyldiiron (5) and trace amount of 4 were obtained. Stirring 5 in refluxing acetonitrile led to the thermal decomposition of 5, and ligand 1 was recovered quantitatively. However, in the presence of excess amount of Fe₂(CO)₉ in refluxing acetonitrile, complex 5 was converted into 2-4. On the other hand, the reaction of N-(6-methyl-2-pyridylmethylidene)-2-thiolethylamine (6) with Fe₂(CO)₉ in refluxing acetonitrile produced 2, μ-[N-(6-methyl-2-pyridylmethyl)-η¹ (N_py);η¹:η¹(N); η¹:η¹(S)-2-thiolatoethylamido]pentacarbonyldiiron (7), and μ-[N-(6-methyl-2-pyridylmethylidene)-η²(C,N);η¹:η¹(S)-2- thiolethylamino]hexacarbonyldiiron (8). Reactions of both complex 7 and 8 with NOBF₄ gave μ-[(6-methyl-2-pyridylmethyl)-η¹(N_py);η¹:η¹(N);η¹:η¹(S)-2-thiolatoethylamido](acetonitrile)tricarbonylnitrosyldiiron (9). These reaction products were well characterized spectrally. The molecular structures of complexes 3, 7-9 have been determined by means of X-ray diffraction. Intramolecular 1,5-hydrogen shift from the thiol to the methine carbon was observed in complexes 3, 7, and 9.     

3-Oxyanthranilic acid derivatives from Actinomadura sp. BCC27169

Eight new compounds including 9′-[2-amino-3-(4″-O-methyl-α-rhamnopyranosyloxy) phenyl]nonanoic acid (1), 9′-[2-amino-3-(4″-O-methyl-α-ribopyranosyloxy)phenyl] nonanoic acid (2), 11′-[2-amino-3-(4″-O-methyl-α-rhamnopyranosyloxy)phenyl]undecanoic acid (3), 11′-[2-amino-3-(4″-O-methyl-α-ribopyranosyloxy)phenyl]undecanoic acid (4), 8-(4′-O-methyl-α-rhamnopyranosyloxy)-3,4-dihydroquinolin-2(1H)-one (5), 8-(4′-O-methyl-α-ribopyranosyloxy)-3,4-dihydroquinolin-2(1H)-one (6), 8-(4′-O-methyl-α-rhamnopyranosyloxy)-2-methyquinoline (7), and 8-(4′-O-methyl-α-ribopyranosyloxy)-2-methylquinoline (8) were isolated from Actinomadura sp. BCC27169. The chemical structures of these compounds were determined based on NMR and high-resolution mass spectroscopy. The absolute configurations of these monosaccharides were revealed by the hydrolysis of compounds 7 and 8. Compounds 3 and 8 exhibited antitubercular activity at MIC 50 μg/mL. Only compound 3 showed cytotoxicity against KB cell at IC₅₀ 18.63 μg/mL, while other isolated compounds were inactive at tested maximum concentration (50 μg/mL).     

Efficient access to chiral N-substituted saccharin analogues via the directed ortho-lithiation of 3-N-arylsulfonyloxazolidin-2-ones

Chiral 3-N-arylsulfonyloxazolidin-2-ones 1a-f, prepared from (l)-amino acids, were reacted with lithium diisopropylamide in anhydrous THF and HMPA. The resulting new, optically active benzisothiazolinone 1,1-dioxides 2a-c and naphthisothiazolinone 1,1-dioxides 2d-f were obtained in good yields.     

Novel and efficient approach to (Z)-4-trifluoroethylidene-1,3-dioxolane derivatives via (trifluoromethyl)ethynylation of ketones and aldehydes

Perfluoroalkylated 4-trifluoroethylidene-1,3-dioxolanes 2a-p were prepared in quantitative yields from the reaction of new stable (trifluoromethyl)ethynylation reagent 1a with TBAF at −15 °C for 10 min, followed by treatment with phenyl perfluoroalkylated ketones at room temperature. The use of aldehydes under the same reaction condition afforded 1,3-dioxolanes 2q-r in good yields. The reaction of 1a with TBAF, followed by treatment with aldehydes or ketones at −15 °C for 10 min and then with trifluoroacetophenone at room temperature provided 1,3-dioxolane derivatives 2s-t in good yields. Tetrabutylammonium trifluoropropynylide [II] was treated with benzaldehyde derivatives at −15 °C for 10 min, followed by treatment with trifluoroacetophenone, to give the corresponding 1,3-dioxolanes 2u-z and 1,3-dioxines 3u-z with different reaction condition.     

Synthesis and decarboxylation of N-acyl-α-triphenylphosphonio-α-amino acids: a new synthesis of α-(N-acylamino)alkyltriphenylphosphonium salts

4-Phosphoranylidene-5(4H)-oxazolones 1 undergo hydrolysis in THF in the presence of HBF₄ at room temperature to give N-acyl-α-triphenylphosphonioglycines 3 (R² = H) in very good yields. 4-Alkyl-4-triphenylphosphonio-5(4H)-oxazolones 2 react with water in CH₂Cl₂/THF solution without any acidic catalyst at 0-5 °C in a few days yielding N-acyl-α-triphenylphosphonio-α-amino acids 3 (R² = Me) or α-(N-acylamino)alkyltriphenylphosphonium salt 4 (R² = CH₂OMe). α-Triphenylphosphonio-α-amino acids 3, on heating up to 105-115 °C under reduced pressure (5 mmHg) or on treatment with diisopropylethylamine in CH₂Cl₂ at 20 °C undergo decarboxylation to give the corresponding α-(N-acylamino)alkyltriphenylphosphonium salts 4, usually in very good yields.     

Unexpected reactions of ferrocene acetal derived from tartaric acid with alkyllithium: competition between proton abstraction and nucleophilic attack

We wished to prepare planar chiral compounds by the lithiation of acetal 2-ferrocenyl-(4S,5S)-bis(methoxymethyl)-1,3-dioxolane (1) with butyllithium followed by the reaction with an electrophile. However, the desired products were not observed and two unexpected products, 1-ferrocenyl-1-pentanol (4) of the nucleophilic attack product and 2-ferrocenyl-4,5-dimethylene-1,3-dioxolane (5) of the proton abstraction product, were isolated. Because the nucleophilic attack on acetal carbon is rarely reported so far and both products 4 and 5 may have some potential uses in organic synthesis, these unexpected reactions are investigated in detail. The mechanisms of these reactions are discussed.     

Antileukemic α-pyrone derivatives from the endophytic fungus Alternaria phragmospora

Four new (1–4) and two known (5 and 6) α-pyrone derivatives have been isolated from Alternaria phragmospora, an endophytic fungus from Vinca rosea, leaves. The isolated compounds were chemically identified to be 5-butyl-4-methoxy-6-methyl-2H-pyran-2-one (1), 5-butyl-6-(hydroxymethyl)-4-methoxy-2H-pyran-2-one (2), 5-(1-hydroxybutyl)-4-methoxy-6-methyl-2H-pyran-2-one (3), 4-methoxy-6-methyl-5-(3-oxobutyl)-2H-pyran-2-one (4), 5-(2-hydroxyethyl)-4-methoxy-6-methyl-2H-pyran-2-one (5), and 5-[(2E)-but-2-en-1-yl]-4-methoxy-6-methyl-2H-pyran-2-one (6). Compounds 2 and 4 showed moderate antileukemic activities against HL60 cells with IC₅₀ values of 2.2 and 0.9 μM and against K562 cells with IC₅₀ values of 4.5 and 1.5 μM, respectively.     

Neutral penta-coordinated diorganotin(IV) complexes derived from ortho-aminophenol Schiff bases: Synthesis, characterization and molecular structures

The one pot reactions carried among ortho-aminophenol, R₂SnO (R = Me or Ph) and acetyl acetone, 2-hydroxyacetophenone and 2-hydroxy-3-methylacetophenone led to six new diorganotin(IV) compounds Me₂SnL1 (1), Ph₂SnL1 (2), Me₂SnL2 (3) Ph₂SnL2 (4), Me₂SnL3 (5) and Ph₂SnL3 (6) (H2L1 = 2-(3-hydroxy-1-methyl-but-2-enylideneamino)-phenol, H2L2 and H2L3 = 2-[1-(2-hydroxyaryl)alkylideneamino]-phenol) in good yields. Combination of IR, ¹H, ¹³C and ¹¹⁹Sn NMR and X-ray diffraction techniques along with elemental analyses evidenced the formation of penta-coordinated monomeric species. The crystal structures of ligand H2L1 and complexes 1, 3 and 4 were determined by single crystal X-ray diffraction study. In the solid state, the ligand H2L1 exists as keto-enamine tautomeric form. There are N-H…O intra-molecular hydrogen bonds between amine and carbonyl groups. Diorganotin(IV) complexes 1, 3 and 4 are monomers with TBP (trigonal bipyramidal) geometry surrounding the tin atom. The O, N, O- tridentate ligand places its two oxygen donating atoms in the axial positions, and the nitrogen atom occupies one equatorial position. The two R groups attached to tin occupy the other two equatorial positions. The solution structures were predicted by ¹¹⁹Sn NMR spectroscopy.     

Synthesis and properties of novel ortho-metalated cobalt(I) and iron(II) complexes through Csp2-H bond activation of dibenzylphenylphosphine

Dibenzylphenylphosphine in the reaction with CoMe(PMe₃)₄ afforded complex [(Me₃P)₃Co((ortho-C₆H₄)∩P(C₆H₅)(CH₂C₆H₅))] (1) by C_sp2-H activation via ortho-metalation with P atom as anchoring group. An unexpected dinitrogen iron(II) complex [(Me₃P)₂(N₂)Fe((ortho-C₆H₄)₂∩P(C₆H₅))] (2) stabilized by two five-membered chelate rings as [CPC]-pincer ligand was formed through the reaction of dibenzylphenylphosphine with FeMe₂(PMe₃)₄ via double C_sp2-H activation. The reactions of complexes 1 and 2 with carbon monoxide delivered carbonyl complexes [(Me₃P)(CO)₂Co((ortho-C₆H₄)∩P(C₆H₅)(CH₂C₆H₅))] (3) and [(Me₃P)₂(CO)Fe((ortho-C₆H₄)₂∩P(C₆H₅))] (4). An iodo methyl cobalt(III) complex [(Me₃P)₂(Me)(I)Co((ortho-C₆H₄)∩P(C₆H₅)(CH₂C₆H₅))] (5) was isolated through the reaction of 1 with iodomethane. The structures of 1, 2, 3, 4 and 5 were determined by X-ray diffraction.     

Syntheses and coordination behaviour of 2-(ortho-phosphinophenyl)-functionalised 1,3-dioxolanes and 1,3-dioxanes towards a [(COD)Rh]-complex fragment - models for immobilised complexes

The syntheses are reported of the ether-phosphine ligands: 2-(ortho-diphenylphosphinophenyl)-1,3-dioxolane (1a), 2-(ortho-diisopropylphosphinophenyl)-1,3-dioxolane (1b), 2-(ortho-diphenylphosphinophenyl)-1,3-dioxane (1c), 2-(ortho-diisopropylphosphinophenyl)-1,3-dioxane (1d). Their reaction with [(COD)RhCl]₂ (COD: 1,5-cyclooctadiene) results in the formation of the mononuclear complexes: {chloro(COD)[2-(ortho-diphenylphosphinophenyl)-1,3-dioxolane]rhodium(I)} (2a), {chloro(COD)[2-(ortho-diisopropylphosphinophenyl)-1,3-dioxolane]rhodium(I)} (2b), {chloro(COD)[2-(ortho-diphenylphosphinophenyl)-1,3-dioxane]rhodium(I)} (2c), and {chloro(COD)[2-(ortho-diisopropylphosphinophenyl)-1,3-dioxane]rhodium(I)} (2d). The chloride ligands of compounds 2a and 2b were abstracted with TlPF₆, with accompanied insertion of an acetal oxygen atom of the ligands 1a and 1b into the coordination sphere of the metal centre, producing {(COD)[η²-P,O-2-(ortho-diphenylphosphinophenyl)-1,3-dioxolane]rhodium(I)}PF₆ (3a∗PF₆) and {(COD)[η²-P,O-2-(ortho-diisopropylphosphinophenyl)-1,3-dioxolane]rhodium(I)}PF₆ (3b∗PF₆). In contrast the dioxane analogues of 3, 3c∗BF₄ and 3d∗BF₄, were formed by reacting the ligands 1c, 1d with [Rh(COD)₂]BF₄. The ligands 1 and the complexes 2 serve as model compounds for their via acetalation to a polyvinylalcohol resin bound analogues. The complexes synthesised were employed as pre-catalysts in the hydroformylation reaction of 1-octene.     

Direct preparation and structure determination of tertiary and secondary amine boranes from primary or secondary amine boranes

New secondary and tertiary amine borane derivatives were prepared in a one-pot reaction starting from primary amine boranes. The reaction involves treatment of an amine borane with 2 equivalents of s-BuLi at −78 °C. In general, mixtures of mono and di metallated products were obtained. Alkyl iodides and benzyl chloride reacted with the lithiated amine, but aldehydes and ketones were reduced. Conversion was high as determined by NMR, but moderate to low yields were obtained after chromatography, possibly due to decomposition on silica. Crystal structures were obtained for the compounds 3a, 3b and 3c.     

Endo and exo cyclometallated iron carbonyl complexes derived from N-(N′-methyl-2-pyrrolylmethylidene)-2-thienylmethylamine

The reaction of N-(N′-methyl-2-pyrrolylmethylidene)-2-thienylmethylamine (1) with Fe₂(CO)₉ in refluxing toluene gives endo cyclometallated iron carbonyl complexes 2 and 5, exo cyclometallated iron carbonyl complex 3, and unexpected iron carbonyl complex 4. Complexes 2, 3, and 5 are geometric isomers. Complex 5 differs from complex 2 in the switch of the original substituent from α to β position of the pyrrolyl ring, and the pyrrolyl ring bridges to the diiron centers in μ-(3,2-η¹:η²) coordination mode in stead of μ-(2,3-η¹:η²). In complex 4, the pyrrolyl moiety of the original ligand 1 has been displaced by a thienyl group, which comes from the same ligand. Single crystals of 2, 3, and 5 were subjected to the X-ray diffraction analysis. The major product 2 undergoes: (i) thermolysis to recover the original ligand 1; (ii) reduction to form a hydrogenation product, 6, of the original ligand; (iii) substitution to form a monophosphine-substituted complex 7; (iv) chemical as well as electrochemical oxidation to produce a carbonylation product, γ-butyrolactam 8.     

A new approach to 2,2-disubstituted 1-(methylsulfanyl)vinyl phosphonates via an intermediate thiocarbonyl ylide

The reaction of methyl (diethylphosphoryl)dithioformate (6) with diaryldiazomethanes 7a-d in THF at −60 °C to room temperature followed by desulfurization is shown to be a convenient method for the preparation of 2,2-disubstituted 1-(methylsulfanyl)vinyl phosphonates 8a-d. The analogous reactions with 2-diazoacenaphthen-1-one (7f) or 2-diazocamphor (7g) in refluxing THF yield selectively the corresponding (Z)- and (E)-vinyl phosphonates 8f and 8g, respectively. These products can be easily oxidized to the vinylsulfoxides 13 and vinylsulfones 14. On the other hand, methyl (diethylphosphoryl)dithioformate (6) and 2-diazo-1,2-diphenylethanone (7e) in boiling THF react to give the 1,3-oxathiole 12. All these reactions occur via an intermediate thiocarbonyl ylide 11 followed by 1,3-dipolar electrocyclization and sulfur extrusion or 1,5-dipolar electrocyclization.     

Cycloaddition of methyl 2-(2,6-dichorophenyl)-2H-azirine-3-carboxylate to electron-rich 2-azadienes

tert-Butyldimethylsililoxy-2-aza-1,3-butadienes react with 2H-azirine 3 leading to Diels-Alder cycloadducts in moderate yields. The reactions are endo- and regioselective with the azirine being added by its less hindered face. There is only one product in the case of 1b, 4b. There are two isomers (4 and 5) from 1a, 1c and 1d. A different result was obtained with the diene 1e. Diene 1e formed products 4e and 8. Some of compounds 4 and 5 have been hydrolysed leading to functionalised aziridines 7. Compound 8 gave aziridine 9.