Stereoselective ring-opening reactions with AcBr and AcCl. A new method for preparation of some haloconduritols

The actions of AcX (X=Br, Cl) on 7-oxa-bicyclo[2.2.1]hept-5-ene-2,3-diol diacetates and a transoid-epoxide prepared from the acetonide of cyclohexa-3,5-diene-cis-1,2-diol were studied. H₂SO₄-catalyzed cleavage of exo-cis-7-oxa-bicyclo[2.2.1]hept-5-ene-2,3-diol diacetate with AcCl gave (1α,2α,3α,6β)-6-chloro-4-cyclohexene-1,2,3-triol triacetate, from which the corresponding chloroconduritol was obtained by trans-esterification (MeOH/HCl). A similar reaction of the exo-diacetate with AcBr in the presence of H₂SO₄ resulted in bromine addition. The formation of bromine from the reaction of AcBr and H₂SO₄ was observed by independent experiments. H₂SO₄-catalyzed reaction of endo-cis-7-oxa-bicyclo[2.2.1]hept-5-ene-2,3-diol diacetate with AcX (X=Br, Cl) gave (1α,2α,3β,6β)-6-halo-4-cyclohexene-1,2,3-triol triacetates. The reaction of the transoid-epoxide with AcX (X=Br, Cl) with no catalyst gave also (1α,2α,3β,6β)-6-halo-4-cyclohexene-1,2,3-triol triacetates.     

Route selection in the synthesis of C-4 and C-6 substituted thienopyrimidines

Three different routes have been investigated for the preparation of 6-aryl-N-(1-arylethyl)thienopyrimidin-4-amines. First the possibilities of selective Suzuki reactions on 6-bromo-4-chlorothienopyrimidine were investigated. The preference for mono arylation at C-6 could be increased, in the case of Pd(PPh₃)₄ catalysis, by reducing the water content of the reaction, or by using less electron rich Pd-ligands. The highest selectivity was obtained with Pd(OAc)₂ or Pd₂(dba)₃, while reactions with the more electron rich Pd(PPh₃)₄ and especially XPhos gave a lower mono- to dicoupled product ratio. Secondly, two alternative strategies avoiding this selectivity issue were tested. Suzuki reaction on C-6 of 6-bromothienopyrimidin-4(3H)-one (three examples) proceeded in 70-89% yield using Pd(PPh₃)₄ in dioxane/water. Similar conditions on 4-amino-6-bromo-thienopyrimidine (eight examples) gave 67-95% yield. The reaction could be performed with boronic acids containing nonprotected phenolic groups in the ortho, meta and para positions. By prolonging the reaction time, coupling with sterically crowded arylboronic acids was also efficient. Diarylation of 6-bromo-4-chlorothienopyrimidine gave the corresponding 4,6-diarylated derivatives in 71-80% yield depending on the nature of the arylboronic acid.     

Trifluoromethyl-containing pyrazolinyl (p-tolyl) sulfones: The synthesis and structure of promising antimicrobial agents

The regiospecific synthesis of a novel series of nine 4-phenyl- and 3-alkyl(aryl)-5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-tosylpyrazoles (pyrazolinyl p-tolyl sulfones), as well as their antimicrobial activity against yeast, such as fungi, bacteria, and alga are reported. The 1-p-tosyl-2-pyrazolines were obtained from the cyclocondensation reaction of 3-phenyl- and 4-alkyl(aryl)-1,1,1-trifluoro-4-alkoxy-3-alken-2-ones, [where alkyl = H, Me and aryl are -C₆H₅, 4-CH₃C₆H₄, 4-OCH₃C₆H₄, 4-FC₆H₄, 4-ClC₆H₄, 4-BrC₆H₄,] with p-tosylhydrazine in a yield of 58-92% when toluene was employed as solvent. The best activity was obtained when the structure possessed a 4-fluorophenyl substituent linked at the carbon-3 of the pyrazoline ring. Subsequently, the dehydration reaction of 3-(4-fluorophenyl) substituted 2-pyrazoline with thionyl chloride/pyridine in benzene as solvent furnished the corresponding 1H-pyrazole in only a moderate yield (49%).     

Superelectrophilic activation of N-aryl amides of 3-arylpropynoic acids: synthesis of quinolin-2(1H)-one derivatives

The superelectrophilic activation of N-aryl amides of 3-arylpropynoic acids by Bronsted superacids (CF₃SO₃H, HSO₃F) or strong Lewis acids AlX₃ (X=Cl, Br) results in the formation of 4-aryl quinolin-2(1H)-ones in quantitative yields. The vinyl triflates or vinyl chlorides may be formed as additional reaction products. The investigated amides in reactions with benzene give 4,4-diaryl 3,4-dihydroquinolin-2-(1H)-ones under the superelectrophilic activation. 4-Aryl quinolin-2(1H)-ones in POCl₃ are converted into 4-aryl 2-chloroquinolines. 4-Fluorophenyl-4-phenyl 3,4-dihydroquinolin-2-(1H)-one give N-formylation products in a yield of 79% under the Vilsmeier–Haack reaction conditions.     

The first synthesis of dihydro-3H-pyrido[2,3-b][1,4]diazepinols and a new alternative approach for diazepinone analogues

The first synthesis of a series of 2-aryl(heteroaryl)-4-trifluoromethyl-4,5-dihydro-3H-pyrido[2,3-b][1,4]diazepin-4-ols, where aryl = C₆H₅, 4-FC₆H₄, 4-ClC₆H₄, 4-BrC₆H₄, 4-CH₃C₆H₄, 4-OCH₃C₆H₄, 4,4′-biphenyl, 1-naphthyl and heteroaryl = 2-thienyl, 2-furyl obtained from the direct cyclocondensation reaction of 4-methoxy-1,1,1-trifluoroalk-3-en-2-ones with 2,3-diaminopyridine in 54-71% yield, is reported. Another alternative and efficient route for the synthesis of a series of 2-aryl(heteroaryl)-3H-pyrido[2,3-b][1,4]diazepin-4(5H)-ones from the reaction 4-methoxy-1,1,1-trichloroalk-3-en-2-ones with 2,3-diaminopyridine, in 54-70% yield, is also reported.     

Generation of oxodiazonium ions 3. Synthesis of [1,2,5]oxadiazolo[3,4-c]cinnoline-1,5-dioxides

A reaction of 4-(N-nitramino)-3-phenylfuroxane with the Ac₂O/H₂SO₄ system leads to the formation of [1,2,5]oxadiazolo[3,4-c]cinnoline-1,5-dioxide, the first representative of furoxanocinnolines. The reaction presumably proceeds through the transformation of the nitramine fragment NHNO₂ to the oxodiazonium ion [N=N=O]⁺ with subsequent intramolecular attack by this cation on the phenyl ring. Furoxanocinnoline is also formed in the reaction of the 4-(N-nitramino)-3-phenylfuroxane O-methyl derivative with H₂SO₄. It is assumed that this reaction also proceeds with involvement of the intermediate cation [N=N=O]⁺ formed by the protonation of the N=N(O)OMe group and subsequent elimination of MeOH. 7-Nitro derivative is formed when furoxanocinnoline is nitrated with the concentrated HNO₃/H₂SO₄ mixture. The compounds obtained were characterized by ¹H, ¹³C, and ¹⁴N NMR spectroscopy.     

Convergent procedure for the synthesis of trifluoromethyl-containing N-(pyridinyl-triazolyl)pyrimidin-2-amines

This study describes a simple and efficient procedure to synthesize a novel series of fourteen 4-substituted N-(5-pyridinyl-1H-1,2,4-triazol-3-yl)-6-(trifluoromethyl)pyrimidin-2-amines, where the 4-substituents are H, CH₃, C₆H₅, 4-FC₆H₄, 4-CH₃C₆H₄, 4-CH₃OC₆H₄ and 2-Furyl; from the cyclocondensation reaction of N-[5-(pyridinyl)-1H-1,2,4-triazol-3-yl]guanidines with 4-alkoxy-4-alkyl(aryl/heteroaryl)-1,1,1-trifluoroalk-3-en-2-ones. The reactions were carried out in ethanol under reflux for 18 h and led to 40-68% yields. N-(Pyridyl-triazolyl)guanidine precursors were further obtained from reactions of cyanoguanidine with nicotinic or isonicotinic acid hydrazides and the halogenated enones from trifluoroacetylation of enolethers or acetals.     

Synthesis of methyl (E)-2-[(3S,4S)-4-hydroxy-3-(pent-3-yloxy)-pyrrolidin-2-ylidene]propanoate and its unusual recyclization

Methyl (2E,4S,5S)-5-hydroxy-6-mesyloxy-2-methyl-4-(pent-3-yloxy)hex-2-enoate was synthesized from l-tartaric acid. Attempted substitution of the mesyloxy group by the reaction with NaN₃ directly led to methyl (E)-2-[(3S,4S)-4-hydroxy-3-(pent-3-yloxy)pyrrolidin-2-ylidene]propanoate. The latter on treatment with CF₃COOH and then NaOH gave methyl (2E)-2-methyl-4-[(S)-oxiran-2-yl]-4-(pent-3-yloxy)but-2-enoate.     

Studies on the radical addition reaction of perfluoroalkyl iodides with 2,3-allenols and the Pd-catalyzed kinetic resolution via Sonogashira coupling reaction

A radical addition reaction promoted by Na₂S₂O₄ of perfluoroalkyl iodides with 2,3-allenols affording E/Z mixtures of 3-iodo-4-perfluoroalkyl-substituted allylic alcohols has been studied. Kinetic resolution with Sonogashira coupling reaction was applied to afford the Z isomer of 3-iodo-4-perfluoroalkyl-substituted allylic alcohol (Z-3) and the E isomer of conjugated enynic diols (E-5) in 39-52% and 22-40% yields, respectively.     

Synthesis and luminescent properties of neutral Eu(III) and Gd(III) complexes with 1-(1,5-dimethyl-1h-pyrazol-4-yl)-4,4,4-trifluoro-1,3-butanedione and 4,4,5,5,6,6,6-heptafluoro-1-(1-methyl-1H-pyrazol-4-yl)-1,3-hexanedione

Neutral [EuL₃Phen] complexes were synthesized by the reaction of EuCl₃ with heterocyclic diketones-1-(1,5-dimethyl-1H-pyrazol-4-yl)-4,4,4-trifluoro-1,3-butanedione and 4,4,5,5,6,6,6-heptafluoro-1-(1-methyl-1H-pyrazol-4-yl)-1,3-hexanedione—and 1,10-phenanthroline (Phen) in an aqueous alcohol solution in the presence of NaOH. The reaction of GdCl₃ with the same diketones under analogous conditions, but without adding 1,10-phenanthroline, yielded [GdL₃(H₂O)₂] complexes. The composition of the complexes was determined by elemental analysis, and their optical and luminescent properties were examined.     

Selective solution-phase synthesis of BiOCl, BiVO4 and δ-Bi2O3 nanocrystals in the reaction system of BiCl3-NH4VO3-NaOH

In this study, we demonstrate a straightforward solution-phase method for the selective synthesis of BiOCl, BiVO₄ and δ-Bi₂O₃ nanocrystals by simply manipulating the reaction temperature and the BiCl₃-to-NaOH mole ratio in the reaction system of BiCl₃-NH₄VO₃-NaOH. The experimental results revealed that BiOCl, as the sole product, was prepared when designating the reaction temperature ranging from room temperature to 100 °C, regardless of the BiCl₃-to-NaOH mole ratio; on the other hand, BiOCl, BiVO₄, and δ-Bi₂O₃ nanocrystals could be selectively prepared at 140-180 °C, depending on the BiCl₃-to-NaOH mole ratio in solution. Significantly, we first report on fabricating δ-Bi₂O₃ sample, the high-temperature cubic phase commonly stabilized at 730-824 °C, at the low reaction temperature of 140-180 °C under solution-phase synthetic conditions. In addition, the δ-Bi₂O₃ sample exhibits strong emission at room temperature.     

Cycloacylation of N-phenyl-N′-R-thioureas with 3-aryl-2-propenoyl chlorides

Cycloalkylation of N-phenyl-N′-R-thiourea with 3-aryl-2-propenoyl chlorides in acetone gives as products 6-aryl-3-phenyl-2-(R-imino)-2,3,5,6-tetrahydro-4H-1,3-thiazin-4-one and their hydrochlorides. The same reaction carried out in acetone in the presence of K₂CO₃ leads to the formation of 6-aryl-3-phenyl-2-(R-imino)-2,3,5,6-tetrahydro-4H-1,3-thiazin-4-ones, N-(3-aryl-2-propenoyl)-N-phenylthioureas, 3-aryl-2-propenoylanilides, and phenyl isothiocyanate.     

Rhodium-catalyzed carbothiolation reaction of 1-alkylthio-1-alkynes

A rhodium complex derived from RhH(PPh₃)₄ and Me₂PhP catalyzed the carbothiolation reaction of 1-alkylthio-1-alkynes and 1,4-diaryl-1,3-butadiynes giving (Z)-4-alkylthio-4-aryl-3-arylethynyl-3-buten-1-ynes. Terminal alkynes such as 1-decyne and (t-butylthio)acetylene underwent the carbothiolation reaction using a RhH(PPh₃)₄-dppb catalyst. The reactions proceeded via cis-addition with C-C bond formation at the less hindered acetylene carbon.     

Stereoselective synthesis and Lewis acid mediated functionalization of novel 3-methylthio-β-lactams

A proficient etiquette for the stereoselective synthesis of novel 3-methylthio-β-lactams and their Lewis acid mediated functionalization is described. Treatment of 2-methylthioethanoic acid and appropriate imines in the Staudinger reaction leads to the stereocontrolled synthesis of novel trans-3-methylthio-β-lactams in excellent yields. cis-3-Chloro-3-methylthio-β-lactams, obtained from stereoselective chlorination of trans-3-methylthio-β-lactams using N-chlorosuccinimide (NCS) and AIBN, were subjected to Lewis acid (TiCl₄ or SnCl₄) mediated functionalization using various active aromatic, heterocyclic and aliphatic compounds (nucleophiles). This reaction provides an easy access to novel, stereoselective cis-3-monosubstituted-3-methylthio-β-lactams, which further undergo smooth desulfurization with Raney-nickel to afford C-3 cis- and trans-monosubstituted-β-lactams. The cis or trans configuration of the hydrogen/chloro/nucleophile substituent at C-3 was assigned with respect to C4–H.     

Catalytic asymmetric hetero-Diels–Alder route to a key intermediate for the synthesis of calyxin L

A catalytic asymmetric formal synthesis of diarylheptanoid natural product calyxin L has been achieved by incorporating an enantio- and diastereoselective hetero-Diels–Alder (HDA) reaction, a Suzuki–Miyaura coupling, and a stereocontrolled catalytic hydrogenation of 2,4,6-trisubstituted dihydropyran as the key steps. The HDA reaction between 4-(4-benzyloxyphenyl)-2-triethylsilyloxy-1,3-butadiene and (4-benzenesulfonyloxyphenyl)propynal catalyzed by dirhodium(II) tetrakis[(R)-3-(benzene-fused-phthalimido)-2-piperidinonate], Rh₂(R-BPTPI)₄, provided cis-2,6-disubstituted tetrahydropyran-4-one in 91% yield with 91% ee.     

Asymmetric syntheses of diarylheptanoid natural products (−)-centrolobine and (−)-de-O-methylcentrolobine via hetero-Diels-Alder reaction catalyzed by dirhodium(II) tetrakis[(R)-3-(benzene-fused-phthalimido)-2-piperidinonate]

Catalytic asymmetric syntheses of (−)-centrolobine and (−)-de-O-methylcentrolobine have been achieved, incorporating a hetero-Diels-Alder (HDA) reaction between 4-aryl-2-silyloxy-1,3-butadienes and phenylpropargyl aldehyde derivatives as a key step. The HDA reaction using dirhodium(II) tetrakis[(R)-3-(benzene-fused-phthalimido)-2-piperidinonate], Rh₂(R-BPTPI)₄, as a chiral Lewis acid catalyst provides exclusively cis-2,6-disubstituted tetrahydropyran-4-ones in up to 93% ee.     

A novel synthesis of new 2-aryl-6-(arylamino)-1H-imidazo[1,2-b]pyrazole-7-carbonitrile derivatives

New 2-aryl-6-(arylamino)-1H-imidazo[1,2-b]pyrazole-7-carbonitriles are synthesized in good yields, via cyclocondensation of 5-amino-1-(2-oxo-2-arylethyl)-3-(arylamino)-1H-pyrazole-4-carbonitriles, which are prepared by the reaction of 5-amino-3-arylamino-1H-pyrazole-4-carbonitriles and α-bromoacetophenone derivatives in the presence of K₂CO₃ using acetone as the solvent.     

Efficient synthesis of functionalized spiro-2,5-dihydro-1,2-λ-oxaphospholes

The reaction of ethyl propiolate with triphenylphosphine (Ph₃P) in the presence of N-alkylisatins led to ethyl 2,2,2-triphenyl-2,5-dihydro-1,2-λ⁵-oxaphosphole-4-carboxylate-spiro-1-alkyl-1,3-dihydro-2H-indol-2-ones in good yield. The reaction of dialkyl acetylenedicarboxylates with Ph₃P in the presence of N-alkylisatins led to dialkyl 2,2,2-triphenyl-2,5-dihydro-1,2-λ⁵-oxaphosphole-3,4-dicarboxylate-spiro-1-alkyl-1,3-dihydro-2H-indol-2-ones and alkyl 4-(alkoxy)-5-oxo-2,5-dihydro-3-furancarboxylate-spiro-1-alkyl-1,3-dihydro-2H-indol-2-ones.     

Synthesis of mononuclear and oligomeric ruthenium(II) acetylides

The complexes trans-[Ru(PMe₃)₄(CCPh)₂] and trans-[Ru(PMe₃)₄(CCC₆H₄C₆H₄CCSnMe₃)₂] have been prepared from the reaction between trans-[Ru(PMe₃)₄Cl₂] and an excess of either Me₃SnCCPh or Me₃SnCCRCCSnMe₃ (R = p-C₆H₄C₆H₄), respectively. However, if only one equivalent of the latter reagent is used the rod-like polymeric species trans-[-Ru(PMe₃)₄CCRCC-]_n can be isolated.     

Derivatives of α,β-dehydroamino acids: V. Intramolecular cyclization of 2-{2-[(<Emphasis Type="Italic">Z</Emphasis>)-1-Benzamido-2-phenylvinyl]acetamidomethyl}benzimidazole

Reaction of 4-benzylidene-2-phenyl-1,3-oxazol-5(4H)-one with 2-(1H-benzimidazol-2-yl)ethaneamine led to the formation of 2-{2-[(Z)-1-benzamido-2-phenylvinyl]acetamidomethyl}benzimidazole that in a reaction with hexamethyldisilazane in DMF gave 5-benzylidene-1-(1H-benzimidazol-2-yl)-2-phenyl-3,5-dihydro-4H-imidazol-4-one. In the presence of K₂CO₃ in dioxane the reaction with hexamethyldisilazane resulted in the product of intramolecular addition, N-(4-benzyl-3-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]-benzimidazol-4-yl)benzamide