Using ligand exchange reactions to control the coordination environment of Pt(II) acetylide complexes: applications to conjugated metallacyclynes

Ligand exchange of cis-bis(diphenylphosphino)ethylene (dppee) with trans-(Ph₃P)₂Pt(CCR)₂ easily generates the cis-complexes (dppee)Pt(CCR)₂ in 64-95% yield. This transformation is used to convert pyridine-containing macrocycle 7 to its cis-analogue 8 and the macrocyclic bipyridine analogue 10 to the unique macrocyclic ligand 11. X-ray structural characterization of trans-complexes 5a and 5b and cis-complexes 6a and 6b are reported, as is the structure of the strained macrocycle 8.     

One-pot synthesis of macrocyclic compounds possessing two cyclobutane rings by sequential inter- and intramolecular [2+2] photocycloaddition reactions

Sensitized photocycloaddition reactions of 6,6′-dimethyl-4,4′-[1,3-bis(methylenoxy)phenylene]-di-2-pyrone (1) with electron-poor α,ω-diolefins such as ethylene diacrylate (2a) and polyoxyethylene dimethacrylates (2b-d) afforded site- and stereoselective macrocyclic dioxatetralactones (3a-d) and (4b) having 18- to 25-membered rings across the C5-C6 and C5′-C6′ double bonds, or C5-C6 and C3′-C4′ double bonds in 1, respectively. Similar photoreactions of 1 with electron-rich α,ω-diolefins such as poly(ethylene glycol)divinyl ether (2e and 2f) afforded crown ether-type macrocyclic compounds (5e and 5f) having 18- and 21-membered rings across the C3-C4 and C3′-C4′ double bonds in 1, respectively. The stereochemical features of 3b, 5e-xx, and 5e-nn were determined by the X-ray crystal analysis. The reaction mechanism was inferred by MO methods.     

Structurally original oxathioethers macrocycles containing an exocyclic double-bond: synthesis,characterization, reactivity,and coordination

New oxathioethers macrocycles have been synthesized and characterized. Each macrocycle consists in structurally defined ether and thioether moieties and an exocyclic double-bond (2a–c) or a hydroxymethyl group (3a–c). Macrocycles (2a–c) have been synthesized by reaction of dianions of thioethers diols (1a–c) with 3-chloro-2-chloromethylprop-1-ene. Their hydroboration/oxidation led to corresponding primary alcohols (3a–c). Structures of compounds (2b) and (3a) have been determined by X-ray diffraction. The reactivity of the hydroxyl group allowed the preparation of oxathioethers macrocycles bearing a polyether chain or a benzyl group (4a,b) and the synthesis of new bicyclic sandwich-type compounds (5a,b). The ability of these functionalized macrocycles to coordinate to palladium has been investigated.     

Novel chiral Schiff base macrocycles containing azobenzene chromophore: gelation and guest inclusion

A novel chiral Schiff base macrocycle 1 was synthesized by [3+3] condensation of enantiomerically pure trans-1,2-diaminocyclohexane with azobenzene-4,4′-dicarbaldehyde. Subsequent reduction of 1 afforded macrocyclic hexamine 2 having three azobenzene units. The former could be converted into a benzene gel, while the latter could include several aromatic guest molecules.     

Anion binding with some 22- and 28-membered selenaaza macrocycles: Structural aspects and Se NMR studies

A series of macrocyclic adducts of the 22- and 28-membered selenaaza macrocycles (1 and 2, respectively) with different counter anions such as halides, sulfate, perchlorate, phosphate, trifluoroacetate and nitrate has been prepared. The adducts have been characterized by elemental analysis, IR, ¹H NMR, ⁷⁷Se NMR and ESI-MS analysis. The ⁷⁷Se NMR spectrum of the adduct (7) shows an upfield shift compared to the parent macrocycle. The bromo (5), iodo (6), sulfate (7), trifluroacetate (10) adducts of the 22-membered selenaaza macrocycle and perchlorate (16), trifluroacetate (18) adducts of the 28-membered selenaaza macrocycle have been structurally characterized. The crystal structures show extensive hydrogen bonding networks. The molecular structures of all the compounds show the macrocycle to be fully protonated except the trifluroacetate adduct of the 22-membered macrocycle (10), which is only diprotonated. The binding constants of the neutral 22-membered selenaaza macrocycle towards, fluoride, bromide, iodide and sulfate ion have been determined by the NMR titration method.     

An efficient microwave assisted synthesis of novel class of Rhodanine derivatives as potential HIV-1 and JSP-1 inhibitors

(Z)-5-(2-(1H-Indol-3-yl)-2-oxoethylidene)-3-phenyl-2-thioxothiazolidin-4-one (7a-q) derivatives have been synthesized by the condensation reaction of 3-phenyl-2-thioxothiazolidin-4-ones (3a-h) with suitably substituted 2-(1H-indol-3-yl)-2-oxoacetaldehyde (6a-d) under microwave condition. The thioxothiazolidine-4-ones were prepared from the corresponding aromatic amines (1a-e) and di-(carboxymethyl)-trithiocarbonyl (2). The aldehydes (6a-h) were synthesized from the corresponding acid chlorides (5a-d) using HSnBu₃.     

Synthesis of polyfunctionalized furans from 3-acetyl-1-aryl-2-pentene-1,4-diones

The BF₃-catalyzed cyclization of 3-acetyl-1-aryl-2-pentene-1,4-diones 1a-e in the presence of water in boiling tetrahydrofuran gave bis(3-acetyl-5-aryl-2-furyl)methanes 2a-e in 26-79% yields along with a small amount of 3-acetyl-5-aryl-2-methylfurans 3a-e. The exact structure of 2a was determined by X-ray crystallography. The use of a half volume of the solvent for the reaction of 1a resulted in the formation of 2,4-bis(3-acetyl-5-phenyl-2-furfuryl)-3-acetyl-5-phenylfuran (4) together with 2a and 3a. A similar reaction of 1a was carried out in the presence of 3-acetyl-5-(4-methylphenyl)-2-methylfuran (3d) to afford 4-(3-acetyl-5-phenyl-2-furfuryl)-3-acetyl-5-(4-methylphenyl)-2-methylfuran (5) in 49% yield. The BF₃-catalyzed reaction of 1a with 2,4-pentanedione in dry tetrahydrofuran at 23°C gave 3-(3-acetyl-5-phenyl-2-furfuryl)-4-hydroxy-3-penten-2-one (6a) and 3-(3-acetyl-2-methyl-4-phenyl-5-furyl)-4-hydroxy-3-penten-2-one (7a) in 66 and 24% yields, respectively. The product distribution depended on the reaction temperature. A similar reaction of 1b-e also yielded the corresponding trisubstituted furans 6b-e and tetrasubstituted furans 7b-e in good yields. These results suggested the presence of the furfuryl carbocation intermediate A during the reaction. The one-pot synthesis of 6a and 7a was also achieved by a similar reaction using phenylglyoxal. The deoxygenation of 1a with triphenylphosphine gave 3a in 88% yield, while 1a was treated with concentrated hydrochloric acid to yield 3-acetyl-2-chloromethyl-5-phenylfuran (8) which was quantitatively transformed in ethanol into 3-acetyl-2-ethoxymethyl-5-phenylfuran (9) and in water into 3-acetyl-5-phenylfurfuryl alcohol (10), respectively. In addition, the Diels-Alder reaction of cyclopantadiene with 1a gave the corresponding [4+2] cycloaddition products 11 and 12.     

Fluorinated molecules relevant to conducting polymer research

The synthesis of versatile fluorine compounds for conducting polymer research on fluorinated materials is presented. 1,2,4,5-Tetrafluorobenzene was converted to 1,2,4,5-tetrafluorobenzaldehyde (1) and protected as an acetal. This gave the acetals 1,2,4,5-tetrafluoro-3-(1,3-dioxol-2-yl)benzene (2a) and 1,2,4,5-tetrafluoro-3-(5,5-dimethyl-1,3-dioxan-2-yl)benzene (2b). Compounds 2a and 2b were converted into the semiprotected 2,3,5,6-tetrafluoroterephthaldehydes: 1,2,4,5-tetrafluoro-3-(1,3-dioxol-2-yl)-6-formylbenzene (3a) and 1,2,4,5-tetrafluoro-3-(5,5-dimethyl-1,3-dioxan-2-yl)-6-formylbenzene (3b). While 3a was easily deprotected to give 2,3,5,6-tetrafluoroterephthaldehyde (4) compound 3b proved very resilient to hydrolysis and gave a 1:1 mixture of 4 and 1,2,4,5-tetrafluoro-3,6-bis(5,5-dimethyl-1,3-dioxan-2-yl)benzene (5). Compound 4 was reduced to 1,2,4,5-tetrafluoro-3,6-dihydroxymethylbenzene (6) and converted into 1,2,4,5-tetrafluoro-3,6-dibromomethylbenzene (7). Compound 7 was finally converted into 1,2,4,5-tetrafluoro-3,6-bis(diethylphosponylmethyl)benzene (8). Compounds 4 and 8 are versatile fluorinated molecules that can be used to replace their hydrogen counterparts in many molecules and materials. To illustrate this compounds 4 and 8 were oligomerised to give partially fluorinated polyphenylenevinylene (9).     

Synthesis and evaluation of bipendant-armed (oligo)thiophene crown ether derivatives as new chemical sensors

Three new (oligo)thiophene bipendant-armed ligands 2a-c, derived from 2-(aminomethyl)-15-crown-5, have been synthesized and characterized. Compounds 2a-c were prepared by reductive amination of the corresponding macrocycle with formyl thiophene derivatives 1a-c in the presence of NaBH(OAc)₃ in fair to good yields. The photophysical properties of ligands 2a-c were studied and they were also evaluated as chemosensors in the presence of Na(I), Ag(I), Pd(II) and Hg(II) cations in acetonitrile solution.     

Microwave-assisted synthesis of novel bis(2-thioxothiazolidin-4-one) derivatives as potential GSK-3 inhibitors

(5Z,5′Z)-3,3′-(1,4-Phenylenebis(methylene)-bis-(5-arylidene-2-thioxothiazolidin-4-one) derivatives (5a-r) have been synthesized by the condensation reaction of 3,3′-(1,4- or 1,3-phenylenebis(methylene))bis(2-thioxothiazolidin-4-ones) (3a,b) with suitably substituted aldehydes (4a-f) or 2-(1H-indol-3-yl)2-oxoacetaldehydes (8a-c) under microwave conditions. The bis(2-thioxothiazolidin-4-ones) were prepared from the corresponding primary alkyl amines (1a,b) and di-(carboxymethyl)-trithiocarbonyl (2). The 2-(1H-indol-3-yl)-2-oxoacetaldehydes (8a-c) were synthesized from the corresponding acid chlorides (7a-c) using HSnBu₃.     

Microwave-assisted manganese(III) acetate based oxidative cyclizations of alkenes with β-ketosulfones

The microwave-assisted synthesis of 5-(4-nitrophenyl)-2-phenyl-4-(phenylsulfonyl)-2,3-dihydrofuran (5a) was performed via manganese(III) acetate based oxidative cyclization of 1-(4-nitrophenyl)-2-(phenylsulfonyl)ethanone (3a) with vinylbenzene (4a). This new protocol was applied to four sulfone derivatives (3a-d), using vinylbenzene (4a) and diphenylethene (4b), affording a series of 2,3-dihydrofurans (5a-d, 6a-d) in moderate to good yields (26-55%). Similar methodology, applied on allylbenzene (4c), surprisingly, led to dehydronaphthalene derivatives (7a-d) in moderate yields. The unexpected mechanism and the role of allylbenzene (4c) are herein discussed.     

Synthesis of arylated highly congested indans using a domino sequence

A novel and efficient regioselective synthesis of various arylated highly congested 7-aryl-5-methylsulfanylindan-4-carbonitriles (3a-f), methyl 7-aryl-5-methylsulfanylindan-4-carboxylates (10a-e) and 7-aryl-5-methylsulfanylindan-4-carboxylic acids (11a-e) through base-catalyzed reaction of 6-aryl-4-methylsulfanyl-2-oxo-2H-pyran-3-carbonitriles (1a-f) and methyl 6-aryl-4-methylsulfanyl-2-oxo-2H-pyran-3-carboxylates (9a-e) by cyclopentanone (2) has been delineated. The synthetic potential of 2-pyranone was explored further to generate molecular diversity using 6-aryl-4-sec-amino-2-oxo-2H-pyran-3-carbonitriles (7a-h), 5,6-diaryl-4-methylsulfanyl-2-oxo-2H-pyran-3-carbonitriles (5a,b) and methyl 5,6-diaryl-4-methylsulfanyl-2-oxo-2H-pyran-3-carboxylates (12a,b) as precursors for the ring transformation by cyclopentanone to assess the effects of substituents on the course of the reaction to obtain highly congested indans, 6,7-diaryl-5-methylsulfanylindan-4-carbonitriles (6a,b), 7-aryl-5-(piperidin-1-yl)indan-4-carbonitriles (8a-h) and methyl 6,7-diaryl-5-methylsulfanylindan-4-carboxylates (13a,b).     

Microwave assisted synthesis of novel imidazo [2,1-b]thiazole derivative attached to quinoxalinones

3-(6-Phenylimidazo[2,1-b]thiazol-5-yl)quinoxalin-2(1H)-ones (qunoxalinone) (6a-q) have been synthesized by the reaction of ethyl 2-oxo-2-(6-phenylimidazo[2,1-b]thiazol-5-yl)acetates (4a-e) with suitably substituted o-phenylenediamines (5a-f) under microwave heating. The ethyl 2-oxo-2-(6-phenylimidazo[2,1-b]thiazol-5-yl)acetates (4a-e) were prepared by the reaction of 6-phenylimidazo[2,1-b]thiazoles (3a-e) with ethyl chlorooxoacetate in refluxing 1,4-dioxane whereas the thiazoles (3a-e) were synthesized by the reaction of 2-bromo-1-phenylethanones (2a-e) with thiazol-2-amine in refluxing acetone.     

Rapid syntheses of (±)-pterocarpans and isoflavones via the gold-catalyzed annulation of aldehydes and alkynes

(±)-Pterocarpan and analogues (4a-c) have been synthesized efficiently via the annulation of salicylaldehydes (1a, 1b and 1c) and o-methoxymethoxylphenylacetylene (2a), followed by a one-pot reduction and acidic cyclization of the ketones (3a-c). In addition, isoflavone derivatives (5a-c) have been synthesized rapidly, in two steps, via the annulation of salicylaldehyde (1a) and arylacetylenes (2b, 2c and 2d), followed by IBX/DMSO oxidation of the isoflavanones (3d, 3e and 3f).     

Facile access to stereodefined dienoates and cyclopropylenoates containing a trifluoromethyl group

Ethyl (2E,4E)-3-trifluoromethyl-2,4-dienoates 1a-e and ethyl (E)-3-trans-alkylcyclopropyl-4,4,4-trifluoro-2-butenoates 2a-e were prepared from the trans-alkenylboronic acids 3a-e and the trans-cyclopropylboronic acids 4a-e with ethyl (Z)-3-iodo-4,4,4-trifluoro-2-butenoate (5) by the Suzuki cross-coupling reaction in high yields (88-95%). The configurations of both 3a-e or 4a-e and 5 were retained in the reaction.     

Diastereoselective route to (2R,5S)- and (2S,5S)-2-methyl-1,6-dioxaspiro[4.5]decane, a pheromone component of the wasp Paravespula vulgaris

A diastereoselective approach to (2R,5S)- and (2S,5S)-2-methyl-1,6-dioxaspiro[4.5]decane 1 and 1a is described. The route starts with an alkylation reaction among the cyclopentanone N,N-dimethylhydrazone 6 and the chiral iodides (R)-3 or (S)-3, derived from the enantiomers of ethyl β-hydroxybutyrate, controlling the estereocenter at C-2 of the molecules. The alkylated products 7 and 7a were easily transformed into the 1,8-O-TBS-1,8-dihydroxy-5-nonanones 9 and 9a in four steps, and a subsequent stereoselective spiroketalization, in acidic media, afforded a Z:E mixture (1:2) of compounds 1 and 1a.     

Synthesis of new tetracyclic 7-oxo-pyrido[3,2,1-de]acridine derivatives

A series of (±)3-hydroxyl- and 2,3-dihydroxy-2,3-dihydro-7-oxopyrido[3,2,1-de]acridines were synthesized for antitumor evaluation. These agents can be considered as analogues of glyfoline or (±)1,2-dihydroxyacronycine derivatives. The key intermediates, 3,7-dioxopyrido[3,2,1-de]acridines (15a,b or 24a,b), for constructing the target compounds were synthesized either from 3-(N,N-diphenylamino)propionic acid (14a,b) by treating with Eaton’s reagent (P₂O₅/MsOH) (Method 1) or from (9-oxo-9H-acridin-10-yl)propionic acid (23a-c) via ring cyclization under the same reaction conditions (Method 2). Compounds 15a,b and 24a,b were converted into (±)3-hydroxy derivatives (25a-d), which were then further transformed into pyrido[3,2,1-de]acridin-7-one (28a-d) by treating with methanesulfonic anhydride in pyridine via dehydration. 1,2-Dihydroxylation of 28a-d afforded (±)cis-2,3-dihydroxy-7-oxopyrido[3,2,1-de]acridine (29a-d). Derivatives of (±)3-hydroxy (25a,b) and (±)cis-2,3-dihydroxy (29a-d) were further converted into their O-acetyl congeners 26a,b and 30a-d, respectively. We also synthesized 2,3-cyclic carbonate (31, 32, and 33) from 29a-c. The anti-proliferative study revealed that these agents exhibited low cytotoxicity in inhibiting human lymphoblastic leukemia CCRF-CEM cell growth in culture.     

Catalyst- and steric-controlled alkenylation via chemoselective C-H activation and C-Br activation in Heck reaction of methyl 1-(2-bromoaryl)-3-(2-furyl/thienyl)-5-oxopyrrolidine-2-carboxylates and diethyl 1-(2-bromoaryl)-3-(2-furyl/thienyl)-5-oxopyrrolidine-2,2-dicarboxylate derivatives

Pd(II)-catalyzed alkenylation of methyl 1-(2-bromoaryl)-3-(2-furyl/thienyl)-5-oxopyrrolidine-2-carboxylate derivatives 1(a-d) resulted in the formation of 3(a-d) exclusively via C-H activation in the heteroaryl moiety. Similar observations were observed for the corresponding diester analogues 4(a-d) to form 5(a-d). Normal Heck reaction, however, was observed in the case of 1(a-f) to furnish 2(a-f) when the reaction was carried out with Pd(0) catalyst generated in situ. Pd(0)-catalyzed vinylation of 4(a-f) via C-Br oxidation, however, failed due to steric reason.     

Solid-state and solution photocycloadditions of 4-acyloxy-2-pyrones with maleimide

Solid-state photosensitized reactions of 4-acyloxy-2-pyrones (1b,c) with maleimide (2) afforded endo-endo double-[4+2] cycloadducts (3b,c) with high stereoselectivity. Sensitized photoreactions of 1a-d with 2 in solution gave exo-endo double-[4+2] cycloadducts (4a-d). 2-Pyrones 1a-d were photolyzed to give carboxylic acids (5a-d) via their valence isomerization in the solid state and in solution. Such kinds of photoreaction of the 4-acyloxy-2-pyrones were dramatically different from regio- and stereoselective [2+2] cycloadditions of 4-alkyloxy-2-pyrones. The photoreaction mechanisms of 1 with 2 and 1 itself were analyzed by powder X-ray diffraction analysis and MO calculations.     

Tetracyclic 1,6-methano-[10]annulenes a novel class of steroidal annulenes

Reaction of 19-hydroxyandrosta-4,6-diene-3,17-dione (8b) and the corresponding Δ⁷-compound (8c) with diethyl-(2-chloro-1,1,2-trifluoroethyl)-amine affords 5β,19-cyclo-Δ^1,6- and 5β,19-cyclo-Δ^1,7-3-ketones (4b) and (4c) respectively. Solvolysis experiments with the 19-tosylates of the 19-hydroxy-Δ^4,6- and Δ^4,7-3-ketones (8b) and 8c) are described as alternate approaches to (4b) and (4c). Exposure of 5β,19-cyclo compounds (4b) and (4c) to acetic anhydride-acetic acid-p-toluenesulfonic acid yields the respective 3-acetoxycycloheptatrienes (5a) and (6a). The latter substance (6a) is converted into the novel tetracyclic 1,6-methano-[10]annulene (2a) on exposure to N-bromosuccinimide in boiling carbon tetrachloride. Synthesis of the corresponding 3-methoxy- and 3-desoxy-1,6-methano-[10]annulenes (2b) and (2c) are also described. The NMR spectra of (2a), (2b) and (2c) and related intermediates are discussed.