One-pot synthesis of malononitriles by free radical reactions of ylidenemalononitrile with Et3B and iodoalkane in a water-ether biphase medium

The one-pot synthesis of malononitrile derivatives 4, 6, and 7 in moderate to high yields by the reaction of ylidenemalononitriles 3, prepared in situ from carbonyl compounds 1 and malononitrile 2 in the presence of ammonium acetate in aqueous solution at 50-60 °C, with Et₃B or RI 5/Et₃B in a water-diethyl ether biphase medium under an atmosphere of room temperature is reported. The reaction of Et₃B with adamantyl iodides 8 and 10 under similar conditions gave 9 and 11 in high yields, respectively. However, low yields of the monoalkylated combined with dialkylated malonates 14 were obtained when benzaldehyde 1a was condensed with dimethylmalonate 12 followed by parallel free radical treatment in benzene solution.     

Sulfinatodehalogenation reactions of gem-aryl disubstituted methylenecyclopropanes with perfluoroiodoalkanes

Sulfinatodehalogenation reaction of gem-aryl disubstituted methylenecyclopropanes (MCPs) 1 with perfluoroiodoalkanes produces the corresponding ring-opened products 4-iodo-1,1-diaryl-2-perfluorobutyl-but-1-enes 2, rearranged products 1,2-dihydronaphthalenes 3, and addition products 1-perfluoroalkyl-1-(diarylmethyl)cyclopropanes 4 in the presence of sodium dithionite in moderate yields through a radical process under mild conditions. The major product 2 is derived from radical ring-opening reaction of MCPs 1.     

Stereoselective hydrostannation of substituted alkynes initiated by triethylborane and reactivity of bulky triorganotin hydrides

This paper reports the results obtained in a study on the radical hydrostannation of mono- and disubstituted alkynes with bulky triorganotin hydrides using triethylborane as initiator. The addition of trineophyl- (1), tris[(phenyldimethylsilyl)methyl]- (2), and 9-tripticyldimethyltin (3) hydride to eight alkynes was carried out at room temperature leading to vinylstannanes in good to excellent yields and, mostly, with complete stereoselectivity. The results obtained in a study on the relative reactivity of trineophyl- (1), tris[(phenyldimethylsilyl)methyl]- (2), 9-triptycyldimethyltin (3) hydrides, and tri-n-butyltin hydride (29) using the radical reactions between these hydrides and 6-bromo-1-hexene (28) are also reported. Full ¹H-, ¹³C-, and ¹¹⁹Sn NMR characteristics are included.     

Synthesis and properties of 7,7-bis(heteroazulen-3-yl)-8,8-dicyano-1,4-quinodimethanes

The synthesis and properties of a novel type of 7,7-bis(heteroazulen-3-yl)-8,8-dicyano-1,4-quinodimethanes (9a-c) are studied. The synthetic method is based on a TFA-catalyzed electrophilic aromatic substitution on the heteroazulenes with 4-(dicyanomethyl)benzaldehyde to afford the corresponding methane derivatives, followed by oxidative hydrogen abstraction with DDQ. The polarization of 9a-c is evaluated by the inspection of their ¹³C NMR and IR spectra. Based on the investigation of the UV-Vis spectra of 9a-c and protonated cations 10a-c, conformational changes of the heteroazulene-moiety and (dicyanomethyl)phenyl group are suggested. In the CV measurements of 9a-c, two reversible reduction waves are observed, indicating the stabilizing ability of heteroazulenes toward the corresponding radical and anion species. Furthermore, 9a-c exhibit two irreversible oxidation waves, which suggest a conformational change in the radical cation during the redox process. The conformational change is rationalized on the basis of the MO calculations.     

Synthesis of fluorine containing glycolurils and oxazolines from oxides of internal perfluoroolefins

The reaction of oxides of internal perfluoroolefins 1-3 with urea gave two kinds of novel fluorine containing N-heterocyclic compounds depending on the solvent nature: 1,5-bis(perfluoroalkyl)tetraazabicyclo[3.3.0]octane-3,7-diones 4a-c and 2-amino-5-fluoro-4,5-bis(perfluoroalkyl)-4,5-dihydrooxazol-4-ols 7a-d. Use of polar dimethylsulfoxide, N,N-dimethylacetamide and acetonitrile afforded glycolurils 4a-c in moderate yields. In dioxane, unexpected cyclization occurred resulting in oxazolines 7a-d in high yields. A similar reaction of oxiranes 2, 3 with urea in aqueous dioxane gave mixtures of 4,5-dihydroxy-4,5-bis(perfluoroalkyl)imidazolidine-2-ones 9b, c, glycolurils 4b, c and oxazolines 7b-d. The molecular structure of trans-isomers of oxazoline 7b and imidazolidine 9b has been established by X-ray crystallography.     

Addition of secondary phosphines to N-vinylpyrroles

Secondary phosphines 1-3 react readily with N-vinylpyrroles 4 and 5 under radical initiation to give regiospecifically anti-Markovnikov adducts, diorganyl-2-(1-pyrrolyl)ethylphosphines 6a-d, highly reactive building blocks for organic synthesis, in 88-91% yields.     

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.     

Synthesis, photophysical and photochemical properties of highly soluble phthalocyanines substituted with four 3,5-dimethylpyrazole-1-methoxy groups

The synthesis and characterization of new peripherally tetra-3,5-dimethylpyrazole-1-methoxy substituted metal-free (4), zinc (5), nickel (6), cobalt (7), copper (8) and lead (9) phthalocyanines are described for the first time in this study. The photophysical (fluorescence quantum yields and fluorescence lifetimes) and photochemical (photodegradation and singlet oxygen quantum yields) properties of metal-free (4), zinc (5) and lead (9) phthalocyanines are studied in dimethylsulfoxide (DMSO). Nickel (6), cobalt (7) and copper (8) phthalocyanines (6-8) did not evaluate for this purpose due to transition metal and paramagnetic behavior of central metals in the phthalocyanine cavity. The fluorescence quenching behavior of metal-free (4), zinc (5) and lead (9) phthalocyanines are also investigated. The fluorescence emissions of these phthalocyanines are effectively quenched by 1,4-benzoquinone in DMSO.     

Radical scavenging activity of sterically hindered catecholate and o-amidophenolate complexes of LSbPh3 type

The radical scavenging effect of the substituted catecholates (1-3, 6) and o-amidophenolates (4, 5) of triphenylantimony(V) in reactions with DPPH^• radical and in a process of oleic acid peroxidation was studied in details. Complexes 1-6 show the high activity in radical scavenging reactions with DPPH^• radical leading to disappearance of radical species. Complexes were demonstrated to be high-efficient inhibitors of chain-radical process of the peroxidation of oleic acid as well as the effective destructors of the formed hydroperoxides. It was found that the effectiveness of complexes studied in the inhibition of the peroxidation of oleic acid depends on the first oxidation potential of complex.     

Copper-catalyzed dimerization of chromium Fischer carbene complexes: synthesis of dialkoxytrienes and their Nazarov-type cyclization to 2-alkoxy-2-cyclopentenones

Fischer carbene complexes 1 underwent a clean ligand dimerization reaction yielding functionalized olefins and trienes 4 in the presence of copper (I) catalysts. If treated with trifluoroacetic acid (TFA), trienes 4c, d, f undergo a cyclization process (Nazarov reaction) which furnishes cyclopentenone derivatives 6c, d, 7c, d and 8 in good yields. Finally, the Fischer aminocarbene 9 efficiently cyclodimerizes to the substituted arene 10 in the presence of CuBr.     

Synthesis of N-tosyl-3,3,4-trisubstituted pyrrolidine derivatives starting from the Baylis-Hillman adducts via radical cyclization

N-Tosyl-3,3-disubstituted-4-vinylpyrrolidine derivatives 3a-c were synthesized via radical cyclization from the modified Baylis-Hillman adducts 2. The required starting materials 2a-c were prepared in moderate yields from the Baylis-Hillman adducts in three steps: (i) acetylation of the Baylis-Hillman adducts, (ii) S_N2′ reaction with tosylamide to prepare 1, and (iii) alkylation with 1,4-dibromo-2-butene.     

Syntheses of aryl- and arylethynyl-substituted N-confused porphyrins

Palladium-catalyzed cross-coupling reactions under Suzuki, Sonogashira, and Stille conditions afford 3-aryl (9-12) and 3-arylethynyl N-confused porphyrin (NCP) silver(III) complexes (13-15) from the 3-bromo NCP complex (4) in ca. 70% yields along with the transmetalated products, 3-substituted NCP palladium(II) complexes (11-Pd to 15-Pd), in 10-30% yields. Substitution at 3-position was confirmed by the single crystal X-ray structures of 9, 13-Ag, and 13-Pd. The arylethynyl groups or five-membered heterocyclic aromatic rings at 3-position largely affected the optical properties of N-confused porphyrin, in which the longest absorption maxima of the Q-bands are shifted bathochromically by 30-120 nm. The electronic effect of substituent differs largely between palladium and silver complexes reflecting the different π-electron delocalization pathway of NCP cores. 3-Aryl- and 3-arylethynyl NCP silver(III) complexes were easily demetalated to afford the corresponding free base porphyrins by the treatment of sodium borohydride.     

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.     

Efficient and regioselective chromium(0)-catalyzed reaction of 2-substituted furans with diazo compounds: stereoselective synthesis of (2E,4Z)-2-aryl-hexadienedioic acid diesters

Pentacarbonyl(η²-cis-cyclooctene)chromium(0) (1) catalyzes efficiently reactions of diazo compounds with electron-rich furans. The reaction of 2-methoxyfuran (2) with alkyl α-diazoarylacetate (3a-g) furnishes the (2E,4Z)-2-aryl-hexadienedioic acid diesters (4a-g) in excellent yields. These reactions are highly regioselective. The cyclopropanation intermediates formed from 1 and diazo compounds 3a-g always arise from a carbene addition to the less substituted CC bond of 2. The resulting cyclopropanation product undergoes a ring opening reaction to form the corresponding (2E,4Z)-2-aryl-hexadienedioic acid diesters (4a-g). The pentacarbonylchromium(0)-catalyzed reactions of 2-alkylfuran (5a-b) with ethyl α-diazophenylacetate (3a) and 9-diazo-9H-fluorene (3h) produce the 1(E),3(E)-butadienes (6a-d) in very good yields.     

A convenient synthesis of pyridine and 2,2′-bipyridine derivatives

α-Chloro-α-acetoxy-β-keto-esters 9 were readily prepared from β-keto-esters 6 in good overall yields. These compounds reacted as α,β-diketo-ester equivalents 2 with amidrazones 1 yielding triazines 3, generally in good yields. Picolinates 10 provided an alternative source of α,β-diketo-ester equivalents 2 when treated with copper(II) acetate. A ‘one-pot’ reaction of the α,β-diketo-ester equivalents 2 with amidrazones 1 in the presence of 2,5-norbornadiene 5 in boiling ethanol yielded the pyridines 4 and 2,2′-bipyridines 4 (R¹=2-pyridyl) directly without the need to isolate the corresponding triazines 3. Triazine 3c reacted with the aza-dienophiles 13 and 17 affording the products 16 and 18, respectively, in good yields.     

Bargellini condensation of coumarins. Expeditious route to o-carboxyvinylphenoxyisobutyric acids and application to the synthesis of sesquiterpenes helianane, heliannuol A and heliannuol C

The direct Bargellini condensation of coumarins involving reaction with chloroform and acetone in the presence of aqueous sodium hydroxide furnished o-carboxyvinylphenoxyisobutyric acids in good yields. The utility of this new useful protocol was demonstrated by the transformation of the three diesters 9b, 9f and 9g to the sesquiterpenes helianane 4, heliannuol A 2 and heliannuol C 3, respectively.     

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.     

Addition of diphenylphosphinodithioic acid and thioacetic acid with vinylidenecyclopropanes: reversed regioselectivities

The reaction of vinylidenecyclopropanes 1 with diphenylphosphinodithioic acid produces the adducts 3 in good to high yields in toluene upon heating at 100 °C within 1 h, whereas adducts 5 are obtained in excellent yields in reversed regioselectivity from the reaction of 1 with thioacetic acid under identical conditions. The radical reaction processes have been discussed on the basis of deuterium labeling experiment and the control experiments in the presence of radical inhibitors (TEMPO and BHT) or a proton scavenger (DTBMP).     

Formation of spiro ketolactones versus alkoxy radical fragmentation-promoted three-atom ring enlarged lactones from cyclic ketones

A dual pathway from readily available 2-allyl-2-carboethoxycycloalkanones 1 provides a new facile stereoselective synthesis either of functionalized spiro ketolactones 4 or of ring enlarged lactones 7 in one-step. Thus, iodination of 5-8-membered 2-allyl-2-carboethoxycycloalkanones 1a-d led, in excellent yields, to spiro ketolactones 4a-d, respectively, as single stereoisomers. On the other hand, iodination of 1a-d under alkoxy radical fragmentation conditions via incipient hemiketals produced the 8-, 9-, 10-, or 11-membered, three-atom ring enlarged, poly-functionalized lactones 7a-c as two stereoisomers and 8 as a single isomer.     

Improved methodologies for synthesis of prenylated xanthones by microwave irradiation and combination of heterogeneous catalysis (K10 clay) with microwave irradiation

Eleven prenylated xanthone derivatives (4-9, 11-15) have been synthesized for the first time by the microwave irradiation method. Prenylation of the xanthone building blocks 1 and 2 with prenyl bromide in alkaline medium, using microwave irradiation, gave the oxyprenylated xanthones 4 and 6, as major products in high yields, as well as diprenylated by-products (5, 7, 8, and 9) in very low yields. Microwave irradiation of oxyprenylated xanthones 4 and 6 furnished three new Claisen rearranged products (11, 14, and 15), as well as the previously described dihydrofuranoxanthones (12, 13). Furthermore, three new (19, 20, 21) and three previously described (16, 17, 18) dihydropyranoxanthones have also been prepared by a one-pot synthesis from xanthones 1, 2, and 3, using Montmorillonite K10 clay as a heterogeneous catalyst and a combination of Montmorillonite K10 clay with microwave irradiation in various conditions. The presence of solvent and the type of the clay (commercial or dry) were found to have a strong influence on the product yields. This is the first report of using these methodologies for the synthesis of dihydropyranoxanthone derivatives. The structures of the prenylated xanthones obtained were established by IR, UV, HRMS, and NMR (¹H, ¹³C, HSQC, and HMBC) techniques.