A facile route to the pentacyclic lamellarin skeleton via Grob reaction between 3-nitro-2-(trifluoromethyl)-2H-chromenes and 1,3,3-trimethyl-3,4-dihydroisoquinolines

The basic structural framework of lamellarin alkaloids, 8,9-dihydro-6H-chromeno[4′,3′:4,5]pyrrolo[2,1-a]isoquinoline derivatives, has been obtained in good yields via Grob reaction between 3-nitro-2-(trifluoromethyl)-2H-chromenes and 1,3,3-trimethyl-3,4-dihydroisoquinolines in refluxing isobutanol. When the reaction was carried out in toluene at room temperature, only Michael adducts, as a mixture of two diastereomers, were isolated.     

Domino reaction of 3-nitro-2-(trifluoromethyl)-2H-chromenes with 2-(1-phenylalkylidene)malononitriles: synthesis of functionalized 6-(trifluoromethyl)-6H-dibenzo[b,d]pyrans and a rare case of [1,5] sigmatropic shift of the nitro group

A variety of functionalized 6-(trifluoromethyl)-6H-dibenzo[b,d]pyrans were easily synthesized in good yields under mild conditions by a domino reaction of 3-nitro-2-(trifluoromethyl)-2H-chromenes with 2-(1-phenylethylidene)- and 2-(1-phenylpropylidene)malononitriles. In the latter case, intermediate 7-amino-10-methyl-10-nitro-9-phenyl-6-(trifluoromethyl)-10,10a-dihydro-6H-benzo[c]chromene-8-carbonitriles were isolated as a result of a rare [1,5] sigmatropic shift of the nitro group.     

Synthesis of 4-(2-hydroxyaryl)-3-nitro-4H-chromenes

A combinatorial library of 4-(2-hydroxyaryl)-3-nitro-4H-chromenes was synthesized in high yield by C4-SMe substitution in N-alkyl/phenyl 4-(methylthio)-3-nitro-4H-chromen-2-amines with a variety of phenols. The reaction always provided C2 substitution in the phenol ring, dictated by hydrogen bond interactions between the phenolic hydroxyl group and the nitro group in 3-nitro-4H-chromenes. Reduction of the nitro group with concomitant hydrolysis of the enamine in 4-(2-hydroxyaryl)-3-nitro-4H-chromenes with Zn, Ac₂O in AcOH furnished hybrid amino-acid lactone incorporating ortho-tyrosine and phenyl alanine moieties.     

Highly diastereoselective 1,3-dipolar cycloaddition of nonstabilized azomethine ylides to 3-nitro-2-trihalomethyl-2H-chromenes: synthesis of 1-benzopyrano[3,4-c]pyrrolidines

Reactions of 3-nitro-2-trifluoro(trichloro)methyl-2H-chromenes, including 2-unsubstituted derivatives, with N-alkyl-α-amino acids (sarcosine, proline) and paraformaldehyde proceed diastereoselectively to give 1-benzopyrano[3,4-c]pyrrolidines in good yields as a result of a 1,3-dipolar cycloaddition of the intermediate nonstabilized azomethine ylide at the Δ³-bond of the chromene system.     

Reactions of 3-nitro-2-trihalomethyl-2H-chromenes with C-nucleophiles. Synthesis of 3-nitro-4-(pyrazol-4-yl)-2-trihalomethylchromanes

The nucleophilic addition of acetylacetone and ethyl acetoacetate at the double bond of 3-nitro-2-trihalomethyl-2H-chromenes in the presence of NaH affords 2,3,4-trisubstituted chromanes containing the β-dicarbonyl fragment at position 4. The trans-trans configuration and the enol structure of the reaction products were confirmed by ¹H NMR spectroscopy and X-ray diffraction. Treatment of these compounds with hydrazine gives the corresponding 3-nitro-4-(pyrazol-4-yl)-2-trihalomethylchromanes. The reactions of 3-nitro-2-trihalomethyl-2H-chromenes with nitromethane and nitroethane in the presence of K₂CO₃ produce 1,3-dinitro derivatives of the chromane series. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1945–1955, November, 2006.     

A simple and convenient synthesis of 4-methyl-3-nitro-2-trihalomethyl-2H-chromenes from N-unsubstituted imines of 2-hydroxyacetophenones and trichloro(trifluoro)ethylidene nitromethanes

The reaction of N-unsubstituted imines of 2-hydroxyacetophenones with trichloro(trifluoro)ethylidene nitromethanes in the presence of DABCO proceeds via tandem oxa-Michael/aza-Henry additions (in dichloromethane) or aza-Michael addition (in benzene) to give 4-methyl-3-nitro-2-trichloro(trifluoro)methyl-2H-chromenes or 1,1,1-trichloro(trifluoro)-3-nitro-N-[1-(2-hydroxyaryl)ethylidene]propan-2-amines, respectively.     

Synthesis of ferrocene annulated trifluoromethylated heterocycles with crispine and lamellarin skeletons

Ferrocene analogues of pyrrolo[2,1-a]isoquinoline alkaloids, 2-(trifluoromethyl)-5,6-dihydroferroceno[g]indolizine and 6-(trifluoromethyl)-8,9-dihydro-6H-chromeno[4,3-b]ferroceno[g]indolizines, were obtained in 44–65% yield via the Grob reaction between 1-nitro-1-(2,2,2-trifluoroethylidene)alkanes or 3-nitro-2-(trifluoromethyl)-2H-chromenes and 1-alkyl-3,4-dihydroferroceno[c]pyridines in 2-propanol at reflux.     

Novel (E)- and (Z)-3(5)-(2-hydroxyphenyl)-4-styrylpyrazoles from (E)- and (Z)-3-styrylchromones: the unexpected case of (E)-3(5)-(2-hydroxyphenyl)-4-(4-nitrostyryl)pyrazoles

An efficient synthetic method for the preparation of (E)- and (Z)-3(5)-(2-hydroxyphenyl)-4-styrylpyrazoles has been developed. The reaction of (E)- and (Z)-3-styrylchromones with hydrazine hydrate afforded the corresponding (E)- and (Z)-4-styrylpyrazoles, respectively, saved 4′-nitro-derivatives where both (E)- and (Z)-4′-nitro-3-styrylchromones afforded (E)-3(5)-(2-hydroxyphenyl)-4-(4-nitrostyryl)pyrazoles. The reaction mechanism for these transformations was discussed and the stereochemistry of all products was assigned by NMR experiments.     

Re-visiting of 5-[(E)-2-(aryl)-1-diazenyl]-quinolin-8-ol with tweaking of Sn-Ph groups: Synthesis, spectroscopic characterization and X-ray crystallography

Reactions of sodium 5-[(E)-2-(aryl)-1-diazenyl]quinolin-8-olates (LH, where the aryl group is an R-substituted phenyl ring such that for L¹H: R = H; L²H: R = 2′-CH₃; L³H: R = 3′-CH₃; L⁴H: R = 4′-CH₃; L⁵H: R = 4′-OCH₃ and L⁶H: R = 4′-OC₂H₅) with Ph₃SnCl in a 1:1 molar ratio yielded complexes of composition Ph₃SnL. The complexes have been characterized by ¹H, ¹³C, ¹¹⁹Sn NMR, IR and ^119mSn Mössbauer spectroscopic techniques in combination with elemental analyses. The crystal structures of Ph₃SnL¹ · 0.5C₆H₆ (1), Ph₃SnL² (2), Ph₃SnL⁵ · C₆H₆ (5) and Ph₃SnL⁶ · 0.5C₆H₆ (6) were determined. The results of the X-ray studies indicated that the benzene solvated compounds 1, 5 and 6 are distorted square pyramid, with one of the phenyl C atoms in the apex while the ligand arrangement around central Sn atom in 2 is distorted trigonal-bipyramidal, with a phenyl C and the oxinato N atoms in axial positions.     

Domino reactions in water for the stereoselective synthesis of novel spiro dihydro-2′H-[indene-2,3′-thiophen]-1(3H)-ones with three contiguous stereocenters

The domino reactions of (E)-2-(aryl)-2,3-dihydro-1H-inden-1-ones and 1,4-dithiane-2,5-diol in the presence of triethylamine in water stereoselectively afforded a library of 2′-(aryl)-4′-hydroxy-4′,5′-dihydro-2′H-spiro[indene-2,3′-thiophen]-1(3H)-ones. This transformation presumably proceeds via the generation of 2-mercaptoacetaldehyde from 1,4-dithiane-2,5-diol followed by Michael addition–intramolecular aldol sequence with C–C and C–S bond formations and creation of three contiguous stereocenters in a one-pot operation.     

Di-n-octyltin(IV) complexes with 5-[(E)-2-(aryl)-1-diazenyl]-2-hydroxybenzoic acid: Syntheses and assessment of solid state structures by Sn Mössbauer and X-ray diffraction and further insight into the solution structures using electrospray ionization MS, Sn NMR and variable temperature NMR spectroscopy

Reactions of 5-[(E)-2-(aryl)-1-diazenyl]-2-hydroxybenzoic acids (LHH′, where the aryl group is an R-substituted phenyl ring such that for L¹HH′: X = H; L²HH′: X=2′-OCH₃; L³HH′: X = 3′-CH₃; L⁴HH′: X = 4′-CH₃; L⁵HH′:X = 4′-Cl) with ⁿOct₂SnO in 2:1 and 1:1 molar ratios have been investigated. Two types of complexes, ⁿOct₂Sn(LH)₂ and {[ⁿOct₂Sn(LH)]₂O}₂, were isolated and they have been characterized by ¹H, ¹³C, ¹¹⁹Sn NMR, ESI-MS, IR and ^119mSn Mössbauer spectroscopic techniques in combination with elemental analyses. The crystal structures of ⁿOct₂Sn(L¹H)₂ (1), {[ⁿOct₂Sn(L²H)]₂O}₂ (3) and {[ⁿOct₂Sn(L³H)]₂O}₂(4) were determined. The mononuclear complex 1 was found to adopt a skew-trapezoidal bipyramidal arrangement around the tin atom while 3 and 4 are centrosymmetric tetranuclear bis(dicarboxylatotetrabutyldistannoxane) complexes containing a planar Sn₄O₂ core in which two μ₃-oxo O-atoms connect an Sn₂O₂ ring to two exocyclic Sn-atoms. The solution structures were confirmed by ¹¹⁹Sn NMR spectroscopy by observing one tin resonance in compound 1 and two tin resonances in {[ⁿOct₂Sn(L⁵H)]₂O}₂ (5). {[ⁿOct₂Sn(L²H)]₂O}₂ (3) and {[ⁿOct₂Sn(L³H)]₂O}₂ (4) undergo very complex exchange processes in deuteriochloroform solution, which has been confirmed by variable temperature ¹H NMR spectroscopy. The cleavage of the most labile bond in the molecule was studied by ESI mass spectrometry.     

Five-membered 2,3-dioxoheterocycles: LXIV. Reactions of 1-methyl-3,4-dihydroisoquinolines with 5-arylfuran-2,3-diones and (Z)-alkyl 4-aryl-2-hydroxy-4-oxobut-2-enoates. Crystal and molecular structure of (2Z,5Z)-3-hydroxy-5-{8,8-dimethyl-2,3,8,9-tetrahydro[1,4]dioxino[2,3-g]isoquinolin-6(7H)-ylidene}-1-phenylpent-2-ene-1,4-dione

5-Arylfuran-2,3-diones and (Z)-alkyl 4-aryl-2-hydroxy-4-oxobut-2-enoates react with 3,3-dialkyl-1-methyl-3,4-dihydroisoquinolines to give (2Z,5Z)-1-aryl-3-hydroxy-5-[3,3-dialkyl-3,4-dihydroisoquinolin-1(2H)-ylidene]pent-2-ene-1,4-diones whose structure has been proved by XRD analysis.     

Synthesis and characterization of bis[dicarboxylatotetraorganodistannoxane] units involving 5-[(E)-2-(aryl)-1-diazenyl]-2-hydroxybenzoic acids: An investigation of structures by X-ray diffraction, NMR, electrospray ionisation MS and assessment of in vitro cytotoxicity

Reactions of 5-[(E)-2-(aryl)-1-diazenyl]-2-hydroxybenzoic acids (LHH′, where the aryl group is an R-substituted phenyl ring such that for L¹HH′: R = H; L²HH′: R = 2′-CH₃; L³HH′: R = 3′-CH₃; L⁴HH′: R = 4′-CH₃; L⁵HH′: R = 4′-Cl; L⁶HH′: R = 4′-Br) with ⁿBu₂SnO in a 1:1 molar ratio yielded complexes of composition {[ⁿBu₂Sn(LH)]₂O}₂. The complexes have been characterized by ¹H, ¹³C, ¹¹⁹Sn NMR, ESI-MS, IR and ^119mSn Mössbauer spectroscopic techniques in combination with elemental analyses. The crystal structures of {[ⁿBu₂Sn(L¹H)]₂O}₂ (1), {[ⁿBu₂Sn(L⁴H)]₂O}₂ (4), {[ⁿBu₂Sn(L⁵H)]₂O}₂ (5) and {[ⁿBu₂Sn(L⁶H)]₂O}₂ (6) were determined. The compounds are centrosymmetric tetranuclear bis(dicarboxylatotetrabutyldistannoxane) complexes containing a planar Sn₄O₂ core in which two μ₃-oxo O-atoms connect an Sn₂O₂ ring to two exocyclic Sn-atoms. The four carboxylate ligands display two different modes of coordination where both modes involve bridging of two structurally distinct Sn-atoms. The solution structures were confirmed by ¹¹⁹Sn NMR spectroscopy by observing two tin resonances in compounds 1, and 4-6. The observed difference between the two tin resonances was about 3 ppm while the differences in ¹³C resonances were even smaller. Compounds {[ⁿBu₂Sn(L²H)]₂O}₂ (2) and {[ⁿBu₂Sn(L³H)]₂O}₂ (3) undergo a very complex exchange processes in deuteriochloroform solution. The in vitro cytotoxic activity of compounds 1 and 4 against WIDR, M19 MEL, A498, IGROV, H226, MCF7 and EVSA-T human tumour cell lines is reported.     

Highly diastereoselective chemoenzymatic synthesis of (2′R)- and (2′S)-2′-deoxy[2′-H]guanosines

In an effort to develop an efficient synthetic method of highly diastereoselective (2′R)- and (2′S)-2′-deoxy[2′-²H]guanosines, chemoenzymatic conversion was investigated. The synthesis of (2′R > 98% de)-2′-deoxy[2′-²H]guanosine was achieved by biological transdeoxyribosylation using (2′R > 98% de)-2′-deoxy[2′-²H]uridine, 2,6-diaminopurine, and Enterobacter aerogenes AJ-11125, followed by treatment with adenosine deaminase. (2′S > 98% de)-2′-Deoxy[2′-²H]guanosine was synthesized from (2′S > 98% de)-2′-deoxy[2′-²H]uridine and 2,6-diaminopurine using thymidine phosphorylase and purine nucleoside phosphorylase instead of E. aerogenes AJ-11125.     

Regioselective synthesis of cytotoxic 4-(1-alkynyl)-substituted 2-(5H)-furanones

4-(1-Alkynyl)-3-bromo- and 4-(1-alkynyl)-3-chloro-2(5H)-furanones have been regioselectively synthesized in moderate to good yields by a new version of the Pd/Cu-catalyzed Sonogashira reaction involving treatment of 1-alkynes with 3,4-dibromo- and 3,4-dichloro-2(5H)-furanone, respectively, in the presence of KF as a base. 4-(1-Alkynyl)-3-bromo-2(5H)-furanones have been found to be able to undergo Stille-type and Suzuki-type reactions with aryl(tributyl)tins and arylboronic acids, respectively, to give 4-(1-alkynyl)-3-aryl-2(5H)-furanones in modest to satisfactory yields. Some 4-(1-alkynyl)-substituted 2(5H)-furanones so prepared have been found to exhibit significant cytotoxic activities, especially against human leukemia cell lines.     

Synthesis, characterization and crystal structures of polymeric and dimeric triphenyltin(IV) complexes of 4-[((E)-1-{2-hydroxy-5-[(E)-2-(2-carboxyphenyl)-1-diazenyl]phenyl}methylidene)amino]aryls

The triphenyltin(IV) complexes of 4-[((E)-1-{2-hydroxy-5-[(E)-2-(2-carboxyphenyl)-1-diazenyl]phenyl}methylidene)amino]aryls (aryls = 4-CH₃, 4-Br, 4-Cl, 4-OCH₃) have been synthesized and characterized by ¹H-, ¹³C-, ¹¹⁹Sn-NMR, ESI mass spectrometry, IR and ^119mSn Mössbauer spectroscopic techniques in combination with elemental analysis. The crystal structures of a representative carboxylate ligand (aryl = 4-CH₃) and three Sn complexes, viz., polymeric (Ph₃Sn[O₂CC₆H₄{NN(C₆H₃-4-OH(C(H)NC₆H₄X-4))}-o])_n (X = Me (1) and Br (2)) and dimeric (Ph₃Sn[O₂CC₆H₄{NN(C₆H₃-4-OH(C(H)NC₆H₄X-4))}-o])₂ (X = OMe (4)) complexes are reported. The coordination environment in each complex is trigonal bipyramidal trans-Ph₃SnO₂. A single zwitterionic carboxylate ligand bridges adjacent Sn atoms via the carboxylate and phenoxide O atoms.     

Nitroketene acetal chemistry: efficient synthesis of 2-amino-3-nitro-4H-chromenes

Base-catalyzed reaction of the nitroketene N,S-acetals and the ring substituted 2-hydroxybenzaldehydes afforded a combinatorial library of the 2-alkylamino-3-nitro-4-alkylsulfanyl 4H-chromenes in excellent yields. Nucleophilic displacement of the C4 alkylsulfanyl group with different thiols afforded 4H-chromenes with structural diversity.     

Library construction of 1-(1H-imidazol-1-yl)-1,2-dihydroisoquinolines via three-component reaction of 2-alkynylbenzaldehyde, amine, and imidazole

Parallel diversity-oriented synthesis of diverse 1-(1H-imidazol-1-yl)-1,2-dihydroisoquinolines via AgOTf-catalyzed three-component reaction of 2-alkynylbenzaldehyde, amine, and imidazole is described. This reaction works efficiently under mild conditions to generate a small library of imidazole-incorporated 1,2-dihydroisoquinolines.     

1-(2′-Pyridylazo)-2-naphtholate (PAN) complexes of rhodium(III): Synthesis,structure and spectral studies

The ligating properties 1-(2′-pyridylazo)-2-naphthol (HPAN) toward Rh(III) have been examined. The reaction of RhCl₃·3H₂O with HPAN in presence of excess PPh₃ afforded trans-[Rh(PAN)Cl(PPh₃)₂]PF₆ (3PF₆). Intermediate cis-[Rh(PAN)Cl₂(PPh₃)] (4) has also been isolated. Solid state structures were authenticated by X-ray analyses revealing that monoanionic PAN is coordinated to rhodium in meridional fashion. Both the compounds were spectroscopically characterized in both solution and solid states, which include IR, NMR (¹H and ³¹P), and optical spectra. The diamagnetic complexes show multiple CT transitions in the visible region. Low-energy transitions (λ ≈ 550–650 nm) occurred in the absorption spectra are predominantly ligand centered in nature. The rhodium(III)–PAN compounds are red emissive (λ_em ≈ 650 nm) at room temperature and the nature of the emission level is probably an ILCT level. Complexes are electro-active in acetonitrile and display irreversible oxidative and reductive waves and these responses are ascribed to be PAN ligand centered in character.     

Synthesis and ring transformations of 1-amino-1,2,3,9a-tetrahydroimidazo[1,2-a]indol-2(9H)-ones

Heating 1-carbamoylmethyl-2,3,3-trimethyl-3H-indolinium chloride in the presence of hydrazine bishydrate produces regioselectively the five-membered heterocycle 1-amino-1,2,3,9a-tetrahydro-9,9,9a-trimethylimidazo[1,2-a]indol-2(9H)-one. The assignment of the structure is based on extensive ¹H, ¹³C and ¹⁵N NMR spectroscopic studies. No ring-chain tautomerism of the 1-amino-1,2,3,9a-tetrahydroimidazo[1,2-a]indol-2(9H)-one was observed to open-chain hydrazides or the corresponding six-membered 1,2,10,10a-tetrahydro[1,2,4]triazino[4,3-a]indol-3(4H)-one. Further transformations of 1-amino-1,2,3,9a-tetrahydroimidazo[1,2-a]indol-2(9H)-one were performed by treatment with aromatic aldehydes, acid chlorides and isocyanates giving access to 40 novel hydrazones, N,N′-diacylhydrazines, N-acyl-N′-carbamoylhydrazines and 1,3,4-oxadiazoles.