Silica-bonded S-sulfonic acid as a recyclable catalyst for chemoselective synthesis of 1,1-diacetates

A simple and efficient procedure for the preparation of silica-bonded S-sulfonic acid (SBSSA) by reaction of 3-mercaptopropylsilica (MPS) and chlorosulfonic acid in chloroform is described. This solid acid is employed as a recyclable catalyst for the synthesis of 1,1-diacetates from aromatic aldehydes and acetic anhydride under mild and solvent-free conditions at room temperature.     

The synthesis of 4,4′-arylmethylene-bis(3-(trifluoromethyl)-1-phenyl-1H-pyrazol-5-ol) in aqueous media without catalyst

The synthesis of 4,4′-arylmethylene-bis(3-(trifluoromethyl)-1-phenyl-1H-pyrazol-5-ol) was performed effectively in aqueous media without catalyst by the reaction of aryl aldehydes and 1-phenyl-3-trifluoromethylpyrazol-5-one. All of the compounds obtained were characterized by elemental analysis, FTIR and ¹H NMR. The structure of compound 3g was further confirmed by the X-ray single crystal diffraction. The method has the advantages of mild condition, without any catalyst, high yields and environmentally benign procedure.     

New and efficient synthesis of 5′-amino-5′-(S)-methyl-2′,5′-dideoxynucleosides

A short, efficient synthesis of 5′-amino-5′-(S)-methyl-2′,5′-dideoxynucleosides 1 has been developed through the diastereoselective addition of methylmagnesium bromide or methyllithium to an intermediate tert-butylsulfinimide.     

Un-catalyzed tandem Knoevenagel–Michael reaction for the synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ols) in aqueous medium

An environmentally benign un-catalyzed one-pot synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ols) has been reported via tandem Knoevenagel–Michael reaction of aldehydes with two equivalents of 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one in aqueous medium.     

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.     

原位生成的Ph3C+均相有机催化剂催化4,4’-芳亚甲基-二（3-甲基-1-苯基-1H-吡唑-5-醇）高效合成（英文）简

Trityl chloride (Ph₃CCl) efficiently catalyzes the condensation of 3-methyl-1-phenyl-1H-pyrazol- 5(4H)-one and aromatic aldehydes under mild and solvent-free conditions, affording 4,4''- (arylmethylene)-bis(3-methyl-1-phenyl-1H- pyrazol-5-ol)s in high to excellent yields and in short reaction time. The presence of the requisite organocatalytic trityl carbocation (Ph₃C⁺) species was confirmed by analysis of infrared, ¹H NMR, and ultra violet spectral data. A plausible mechanism was proposed for the reaction based on the observations and literature precedent.     

Synthesis of substituted 3-(3-chloro-1H-pyrazol-5-yl)quinoxalin-2(1H)ones

Synthetic strategies to gain access to all four isomers of 3-(3-chloro-1H-pyrazol-5-yl)quinoxalin-2(1H)ones with monosubstituted benzo core (i.e., compounds 8a–d) are described. Preparation of these heterocyclic compounds succeeded starting from only two different substituted 2-nitroanilines (i.e., 3-methoxy- and 4-methoxy-2-nitroaniline) in three or five steps, respectively.     

Synthesis of (3′R,5′S)-3′-hydroxycotinine using 1,3-dipolar cycloaddition of a nitrone

To synthesize (3′R,5′S)-3′-hydroxycotinine [(+)-1], the main metabolite of nicotine (2), cycloaddition of C-(3-pyridyl)nitrones 3a, 3c, and 15 with (2R)- and (2S)-N-(acryloyl)bornane-10,2-sultam [(2R)- and (2S)-8] was examined. Among them, l-gulose-derived nitrone 15 underwent stereoselective cycloaddition with (2S)-8 to afford cycloadduct 16, which was elaborated to (+)-1.     

Synthesis and properties of novel 5-(cyclohepta-2′,4′,6′-trienylidene)pyrimidine-2(1H),4(3H),6(5H)-triones: methodology for synthesizing cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborates

Novel condensation reaction of tropone with N-substituted and N,N′-disubstitued barbituric acids in Ac₂O afforded 5-(cyclohepta-2′,4′,6′-trienylidene)pyrimidine-2(1H),4(3H),6(5H)-trione derivatives (8a-f) in moderate to good yields. The ¹³C NMR spectral study of 8a-f revealed that the contribution of zwitterionic resonance structures is less important as compared with that of 8,8-dicyanoheptafulvene. The rotational barriers (ΔG^‡) around the exocyclic double bond of mono-substituted derivatives 8a-c were obtained to be 14.51-15.03 kcal mol⁻¹ by the variable temperature ¹H NMR measurements. The electrochemical properties of 8a-f were also studied by CV measurement. Upon treatment with DDQ, 8a-c underwent oxidative cyclization to give two products, 7 and 9-substituted cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborates (11a-c·BF₄⁻ and 12a-c·BF₄⁻) in various ratios, while that of disubstituted derivatives 8d-f afforded 7,9-disubstituted cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborate (11d-f·BF₄⁻) in good yields. Similarly, preparation of known 5-(1′-oxocycloheptatrien-2′-yl)-pyrimidine-2(1H),4(3H),6(5H)-trione derivatives (14a-d) and novel derivatives 14e,f was carried out. Treatment of 14a-c with aq. HBF₄/Ac₂O afforded two kinds of novel products 11a-c·BF₄⁻ and 12a,c·BF₄⁻ in various ratios, respectively, while that of 14d-f afforded 11d-f. The product ratios of 11a-c·BF₄⁻ and 12a-c·BF₄⁻ observed in two kinds of cyclization reactions were rationalized on the basis of MO calculations of model compounds 20a and 21a. The spectroscopic and electrochemical properties of 11a-f·BF₄⁻ and 12a-c·BF₄⁻ were studied, and structural characterization of 11c·BF₄⁻ based on the X-ray crystal analysis and MO calculation was also performed.     

A simple route for the synthesis of 3,3,3′,3′-tetramethyl-2,3,3′,4′-tetrahydro-1H,1′H-[4,9′-bixanthene]-1,1′(2′H,9′H)-dione and its derivatives catalyzed by Mn and other transition metal cations

A simple and efficient unusual coupling reaction of 9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one and its derivatives was accomplished in the presence of Mn²⁺, Cu²⁺, Cd²⁺, Hg²⁺, Fe³, or La³⁺. The structure elucidation was accomplished by IR, ¹H NMR, ¹³C NMR, X-ray crystallography, UV-Visible and elemental analysis. A reaction mechanism is proposed.     

A novel one-pot and efficient procedure for the synthesis of 3H-spiro[isobenzofuran-1,6′-pyrrolo[2,3-d]pyrimidine]-2′,3,4′,5′-tetraones

A novel and practical one-pot procedure is described for the preparation of several new of 3H-spiro[isobenzofuran-1,6′-pyrrolo[2,3-d]pyrimidine]-2′,3,4′,5′-tetraones based on the addition reaction of ninhydrin and 6-aminouracils followed by oxidative cleavage of their corresponding dihydroxyindenopyrrolopyrimidines.     

An efficient synthesis of new 1-H-4′-methyl-3′,4′-dihydrospiro[piperidine-4,2′(1′H)quinoline] scaffolds

Efficient synthesis of new 3′,4′-dihydrospiro[piperidine-4,2′(1′H)quinolines] by a four step synthetic route based on 1-benzyl-4-piperidone reactivity 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.     

Synthesis and characterization of 9-methyl-2-morpholin-4-yl-8-substituted phenyl-1H-purine derivatives using polyphosphoric acid (PPA) as an efficient catalyst

We demonstrate the synthesis of various purine derivatives through the coupling of N⁴-methyl-2-morpholin-4-yl-pyrimidine-4,5-diamine with various aldehydes by using polyphosphoric acid (PPA) as an efficient catalyst in DMF at reflux temperature. The PPA catalyst gave better yields (70-85%) in short reaction times (45-60 min). This commercially available cheap catalyst is more active than many reported expensive catalysts. Many aldehydes underwent the above conversion to form a series of 9-methyl-2-morpholin-4-yl-8-phenyl-9H-purines.     

Silica-bonded N-propyl sulfamic acid as an efficient recyclable catalyst for the synthesis of 3,4-dihydropyrimidin-2-(1H)-ones/thiones under heterogeneous conditions

Silica-bonded N-propyl sulfamic acid(SBNPSA) catalyzed one-pot three component Biginelli condensation of different substituted aromatic aldehydes with ethyl acetoacetate and urea/thoiurea to the respective 3,4-dihydropyrimidin-2-(1H)-ones and thiones in environment friendly procedure is described. The facile reaction conditions, simple isolation and purification procedures of this method make it a good option for the synthesis of dihydropyrimidinones.     

Asymmetric synthesis of (−)-(S,S)-homaline

The asymmetric synthesis of (−)-(S,S)-homaline was achieved in 8 steps from commercially available starting materials using the diastereoselective conjugate addition of the novel lithium amide reagent lithium (R)-N-(3-chloropropyl)-N-(α-methyl-p-methoxybenzyl)amide to methyl cinnamate to install the correct stereochemistry. Subsequent functional group manipulation of the resultant β-amino ester and Sb(OEt)₃-mediated macrolactamisation was followed by homodimerisation to give (−)-(S,S)-homaline in 18% overall yield, representing the first asymmetric, and by far the most efficient synthesis of this natural product reported to date.     

Application and details of photoinduced oxidative cyclization of 5-(4′,9′-methanocycloundeca-2′,4′,6′,8′,10′-pentaenylidene)pyrimidine-2,4,6(1,3,5H)-triones and related compounds

As novel methodology for synthesizing the furan ring, a photoinduced oxidative cyclization of 5-(4′,9′-methanocycloundeca-2′,4′,6′,8′,10′-pentaenylidene)pyrimidine-2,4,6(1,3,5H)-triones (7a-c) and related compounds 9a-c was accomplished to give 5,10-methanocycloundeca[4,5]furo[2,3-d]pyrimidine-2,4(1,3H)-dionylium tetrafluoroborates (8a-c⁺·BF₄⁻) and related compounds 2a-c⁺·BF₄⁻, respectively. In the photoinduced oxidative cyclization, the molecular oxygen in air is used as oxidant and the reaction proceeds under mild conditions to give desired products without byproducts, and thus, it is interesting from the viewpoint of the green chemistry. On the reactions of the mono-substituted derivatives 7d,e and 9e,f, the selectivity of the photoinduced cyclizations were reversed as compared with those of the DDQ-promoted oxidative cyclizations. By the NMR monitoring of the reactions of 7a and deuterated compound 7a-D₂ under degassed conditions, the details of the reaction pathway were clarified and rationalized on the basis of the MO calculation by the 6-31G^∗ basis set of the MP2 levels as well.     

3-Methyl-4H-[1,2,4]-oxadiazol-5-one: a versatile synthon for protecting monosubstituted acetamidines

The utilization of 3-methyl-4H-[1,2,4]-oxadiazol-5-one as a versatile protected acetamidine is demonstrated through employment in a variety of synthetic sequences. The potassium salt (2a) or the neutral form (2b) is alternatively shown to be superior for various synthetic reactions (i.e., alkylation, Michael addition, Mitsunobu) to incorporate side chains for further synthesis. The 3-methyl-4H-[1,2,4]-oxadiazol-5-one moiety was found to be stable to acid or base under non-aqueous conditions. It was also found to be stable to many reagents commonly used for organic synthesis. Despite this stability, the free acetamidine may be released by mild reduction including Lindlar hydrogenation or dissolving metal reductions. Alternatively, the hydroxyl amidine may be formed via alkaline hydrolysis.     

A convenient and new approach to the synthesis of ω-heterocyclic amino acids from carboxy lactams through ring-chain-transformation. Part 2: Synthesis of (2R)-/(2S)-2-aminomethyl-3-(1-aryl-/1,5-diaryl-1H-pyrazol-3-yl)-propionic acid

Making use of amide activation, a convenient and short path synthesis of optically pure ω-heterocyclic-β-amino acids has been achieved from (1R,3R)- and (1R,3S)-5-oxo-1-(1-phenyl-ethyl)-pyrrolidine-3-carboxylic acid methyl ester. The key step of the synthesis involves a regiospecific ring-chain-transformation of the enaminones when subjected to 1,2-binucleophilic attacks. The method is illustrated by the synthesis of (2R)-/(2S)-2-aminomethyl-3-(1-aryl-/1,5-diaryl-1H-pyrazol-3-yl)-propionic acid.     

A hetero-Diels-Alder approach to functionalized 1H-tetrazoles: synthesis of tetrazolyl-1,2-oxazines, -oximes and 5-(1-aminoalkyl)-1H-tetrazoles

This work describes the first and unprecedented examples of inverse electron demand Diels-Alder reactions of 5-(1-nitrosovinyl)-1-phenyl-1H-tetrazole, generated in situ from the corresponding bromooxime, with electron rich alkenes and heterocycles, providing in good overall yields tetrazolyl-1,2-oxazines and -oximes. Upon subsequent reduction these allowed the access to 5-(1-aminoalkyl)-1H-tetrazoles, paving the way for a new entry into this important class of compounds, bioisosteres of α-amino acids.