Diastereoselective Michael additions of N-Boc-2-(tert-butyldimethylsiloxy)pyrrole to 2-(Arylsulfinyl)-1,4-benzoquinones

Reactions of 2-(arylsulfinyl)-1,4-benzoquinones 1a-c with N-(tert-butoxycarbonyl)-2-(tert-butyldimethylsiloxy)pyrrole 2 have been studied under different catalytic conditions. Under BF(3).OEt(2) catalysis, reactions were completely stereoselective leading to the Michael-type adducts 3, whereas in the presence of SnCl(4) diastereomeric mixtures of the pyrrolo[3,2-b]benzofuranes 5 and 6 were obtained. The latter products result from a tandem process involving the Michael reaction followed by an intramolecular cyclization of the intermediates 3 and 4, the first step being hardly stereoselective. Reactions catalyzed by Eu(fod)(3) evolved in a highly stereoselective manner yielding the products 3 or 5 depending on the electronic density of the arylsulfinyl group.     

5-(2’-羧乙基)-6-烷基-3,4-二氢吡喃酮的合成

吡喃酮是许多天然产物的结构单元,我们曾由4-异丁酰基庚二酸在过量醋酸酐及乙酰氯存在下回流得到7-氧代-8,8-二甲基-△~9-六氢香豆素.本文由二氰乙基-β-二酮进行酮解水解反应得到4-酰基庚二酸1_(a-c)。 在过量醋酸酐、乙酰氯存在下由1_a、1_c为底物进行反应没有得到双环的香豆素衍生物.其产物和单纯以乙酐为缩合剂时的产物2_a、2_c相同,产率分别为68％、63％。2_c可在硫酸铁催化     

Hypbrvalent Iodine Oxidation of 3-(2-Furyl)-1-(2-hydroxyaryl)prop-2-enones : Synthesis of Novel 2-(2-Furyl)-cis-3-hydroxvchromanones and Derived 3-Hydroxychromones

The synthesis of novel 2-(2-furyl)-cis-3-hydroxychro-manones(3a-c) has been achieved from 3-(2-furyl)-1-(2-hydroxy-aryl)-2-enones (1a-c) via acid catalyzed hydrolysis of dimethylacetals (2a-c), formed by hypervalent iodine oxidation using iodobenzene diacetate in methanolic potassium hydroxide. Action of dil. alkali on 3a and 3b provides a new synthesis of 2-(2-furyl)-3-hydroxychromones (6a, 6b).     

Photolytic, thermal, addition, and cycloaddition reactions of 2-diazo-5,6- and -3,8-disubstituted acenaphthenones

Preparation and varied thermal and photolytic reactions of 2-diazo-5,6-(disubstituted)acenaphthenones (11a-d) and 2-diazo-3,8-dimethoxyacenaphthenone (12) are reported. Alcohols react thermally and photolytically with 11a-c with losses of N(2) to yield 2-alkoxynaphthenones (24a,band 47a,b) and acenaphthenones (25 and 48a,b). Aniline and diphenylamine are converted by 11a-c at 180 degrees C to acenaph[1,2-b]indoles (29a,b and 53a,b). Thermolyses of 11a-c at approximately 450 degrees C (0.15 mmHg) yield reduction products 25 and 48a,b, respectively. Wolff rearrangements to 1,8-naphthyleneketenes (15a-d) and/or their derivatives are not observed in the above experiments. Oxygen converts 11a-c thermally to acenaphthenequinones (19a-c) and/or 1,8-naphthalic anhydrides. Insertion, addition, substitution, and/or isomerization reactions occur upon irradiation of 2-diazoacenaphthenones in cyclohexane, benzene, and tetrahydrofuran. Photolysis of 11d in benzene in the presence of O(2) yields the insertion-oxidation product 2-hydroxy-5,6-dinitro-2-phenylacenaphthenone (60). Photolyses of 11a-c in nitriles result in N(2) evolution and dipolar cycloaddition to give acenaph[1,2-d]oxazoles (41 and 61a,b). Acetylenes undergo thermal and photolytic cycloaddition/1,5-sigmatropic rearrangement reactions with 11a-d with N(2) retention to give pyrazolo[5,1-a]quinolin-7-ones (69f-j). 2-Diazoacenaphthenones 1a and 11a react thermally and photolytically with electronegatively-substituted olefins with N(2) expulsion to yield (E)- and (Z)-2-oxospiro[acenaphthylene-1(2H),1'cyclopropanes] 73a-c and 74a-c, respectively. The mechanisms of the reactions of 1a, 11a-d, and 12 reported are discussed.     

Photocyclization of 2-[1]benzothien-3-yl)-3-phenylpropenoic acids

Photocyclization of the substituted 2-([1]benzothien-3-yl)-3-phenylpropenoic acids 3a-c in the presence of iodine and air in a benzene-cyclohexane mixture afforded a separable mixture of three compounds, benzo[b]naphtho[2,1-d]thiophene-6-carboxylic acids 4a-c , 6H-benzo[b]naphtho[2,3-d]thiopyran-6-ones 5a-c , and 10-methoxy-2-methyl-6H-benzo[b]naphtho[2,3-d]pyran-6-one ( 6 ).     

Asymmetric Synthesis. 39.(1) Synthesis of 2-(1-Aminoalkyl)piperidines via 2-Cyano-6-phenyl Oxazolopiperidine

The asymmetric synthesis of a series of 2-(1-aminoalkyl) piperidines using (-)-2-cyano-6-phenyloxazolopiperidine 1 is described. LiAlH(4) reduction of 1 followed by hydrogenolysis led to the diamine 3. The same strategy applied to C-2-methylated compound 7 afforded [(2S)-2-methylpiperidin-2-yl]methanamine (9). Addition of lithium derivatives to the cyano group of 1 resulted in the formation of an intermediate imino bicyclic system (11a-c) which could be diastereoselectively reduced to substituted diamino alcohols 13a-c. The addition of an excess of PhLi to 1 in the presence of LiBr furnished disubstituted amine 19, the precursor of diphenyl[(2S)-piperidin-2-yl]methanamine (22).     

Potassium Fluoride Promoted Reaction of 3-Acylsubsti-Tuted 2H-1-Benzopyran-2-Ones with Acid Anhydrides. An Improved Method for the Synthesis of 4-(2-Oxoalkyl)-2H-Chroman-2-Ones. Part III1

The reaction of 3-acylsubstituted 2H-1-benzo-pyran-2-ones 1, 5 and 11a-c with acid anhydrides in the presence of potassium fluoride (KF)/molecular sieves 4A gives the 4-(2-oxoalkyl)-2-oxochromans 2, 6 and 12a-c as the main products. Also the 3-carboxylic acid derivatives, such as esters and N,N-dialkylamides, of 2H-1-benzopyran-2-one (11d-g) react with isobutyric acid anhydride in the presence of KF/molecular sieves 4A to give the corresponding 2-oxochroman-4-acetic acid derivatives.     

Facile syntheses of 2,2-dimethyl-6-(2-oxoalkyl)-1,3-dioxin-4-ones and the corresponding 6-substituted 4-hydroxy-2-pyrones

A variety of 2,2-dimethyl-6-(2-oxoalkyl)-1,3-dioxin-4-ones 5a-l and the corresponding 6-substituted 4-hydroxy-2-pyrones 3a-l were prepared in high yields under mild reaction conditions by the reaction of 2,2,6-trimethyl-1,3-dioxin-4-one 4 with 1-acylbenzotriazoles 9 in the presence of LDA followed by thermal cyclization of 5a-l to 3a-l. Synthesis of novel 6-(1-benzoylalkyl)-2,2-dimethyl-1,3-dioxin-4-ones 12a-c was achieved by alkylation of dioxinone 5a and their subsequent cyclization gave 5-alkyl-4-hydroxy-2-pyrones 13a-c.     

Microwave assisted synthesis of novel functionalized hydantoin derivatives and their conversion to 5-(Z) arylidene-4H-imidazoles

2-(Alkyl-1-yl)-1H-imidazol-5(4H)-ones 5a-n were synthesized via nucleophilic substitution of the methylsulfanyl group of the corresponding 2-(methylthio)-1H-imidazol-5(4H)-ones 3a-c with suitably substituted secondary amines. The starting 2-thioxo- imidazolidin-4-ones 2a,2b were prepared by condensation of thiohydantoin and benzo[b]-thiophene-3-carbaldehyde or benzofuran-3-carbaldehyde under microwave irracdiation (MW) conditions. 2-Methylthio derivatives 3a-c were prepared by treatment of 2a-b with methyl iodide in the presence of aqueous sodium hydroxide.     

1-(Organosulfonyloxy)-3(1H)-1,2-benziodoxoles: Preparation and Reactions with Alkynyltrimethylsilanes

Organosulfonyloxy derivatives of 1,2-benziodoxol-3(1H)-one (3a-c) and 3,3-bis(trifluoromethyl)-3(1H)-1,2-benziodoxole (5a-c) can be prepared in high yield by the reaction of 1-hydroxybenziodoxoles 1 or 4 and the corresponding sulfonic acids or Me(3)SiOTf in the form of stable, but moderately hygroscopic, microcrystalline solids. Reaction of the triflate derivatives 3a and 5a with alkynyltrimethylsilanes affords either alkynyliodonium triflates 6, or (E)-beta-(trifluoromethanesulfonyloxy)alkenyliodonium triflates 7, while the same reaction in the presence of pyridine selectively gives the respective 1-alkynylbenziodoxoles 8 and 9 in 82-90% yield.     

New oxidative cyclizations of 1,3,4,6-tetraketones. Synthesis and structure of (Z)-2-acyl-5-alkyl(aryl)-1,4-dioxaspiro[2.4]hept-5-en-7-ones

Iodosobenzene diacetate oxidation of 1,3,4,6-tetraketones 1a-c yielded (Z)-2-acyl-5-alkyl(aryl)-1,4-dioxa-spiro[2.4]hept-5-en-7-ones (4a-c) in addition to 2-acyl-6-alkyl(aryl)-3-hydroxy-4-pyrones (3a-c). The structure of new spiro-heterocycles 4 was inferred from chemical and spectroscopic data, and the stereochemistry was fully defined by a single-crystal X-ray analysis. Alternative cyclization pathways can be rationalized as proceeding through carbocation intermediates derived from both forms of the ring-chain tautomerism of 1,3,4,6-tetraketones 1.     

Reactions of 2-hydroxybenzonitrile with isocyanates

Triethylamine catalyzes the reaction of 2-hydroxybenzonitrile ( 1 ) with aryl isocyanates to form the corresponding carbamates 2a-c , as well as the cyclization of the latter compounds to either 4[N-(N-arylcarbamoyl)-imino]-3-aryl-2H-1,3-benzoxazin-2-ones 4a-c , or 4-arylamino-2H-1,3-benzoxazin-2-ones 7a-c , depending on the reaction temperature. Under analogous conditions, the carbamates obtained from 1 and 2-chloroethyl isocyanate, 3-chloropropyl isocyanate and ethyl isocyanatoacetate undergo a double cyclization yielding imidazo- and pyrimido[1,2-c|1,3]benzoxazinones 13a,b,17 . Upon heating in phenyl ether, compounds 7a-c , rearrange to 2-(2-hydroxyphenyl)-4(3H)-quinazolinones 10a-c .     

Synthesis and biological activities of 1-[2-(dimethylamino)ethyl]- and 1-[3-(dimethylamino)propyl]-substituted 3-methyl-1,8-dihydrocycloheptapyrazol-8-ones and related compounds.

3-Methyl-1,8-dihydrocycloheptapyrazol-8-ones (2a-c), prepared from 3-acetyltropolones (1a-c), were treated with diazomethane, methyl iodide, dimethyl sulfate, and diethyl sulfate to give 1- and 2-alkylated compounds. The 1,8-dihydrocycloheptapyrazol-8-one (2a) also reacted with 2-(dimethylamino)ethyl, 2-(diethylamino)ethyl, 3-(dimethylamino)propyl, and 2,3-dihydroxypropyl chloride to afford the corresponding 1-substituted products. A preliminary study was made of the biological activities of some of the obtained compounds.     

Reactions of 3-isopropenyltropolones with bromine and N-bromosuccinimide: Formation of 8H-cyclohepta[b]furan-8-one derivatives

3-Isopropenyltropolones 1a-c were treated with bromine in carbon tetrachloride to give 3-methyl-8H-cyclohepta[b]furan-8-ones 2a-c and their corresponding 7-bromo-substituted compounds 3a-c , while reactions in acetic acid gave the bromo-substituted compounds 3a-c . On the other hand, bromination of 1a-c with N-bromosuccinimide afforded 7-bromo-3-(2-bromo-1-methylethenyl)tropolones 5a-c . The compound 2a was treated with bromine to give 2-bromo-3-methyl-8H-cyclohepta[b]furan-8-one ( 4 ). The tropolones 5a-c were heated in the presence of potassium carbonate to give the cyclized compounds 3a-c .     

Infrared, 1H and 13C NMR spectra, structural charcterization and DFT calculations of novel adenine-cyclodiphosp(V)azane derivatives

Adenine tetrachlorocyclodiphospha(V)zane derivatives (III(a-c)) were prepared by the reaction of hexachlorocyclodiphospha(V)zane derivatives (I(a-c)) and adenine (II) as precursors. The synthesized compound's and their structures (III(a-c)) were firmly characterized (based on the presence of an inversion center) using FT-IR (4000-200 cm(-1)), UV-vis. (190-800 nm), (1)H, (13)C NMR and Mass spectral measurements in addition to C, H, N, P elemental analysis. The compounds (III(a-c)) were found to be a 1:2 molar ratio of (I(a-c)) and adenine (II) adducts, respectively. Confident and complete vibrational assignments are proposed for nearly all fundamental vibrations, along with detailed interpretation for all observed signals in both (1)H and (13)C NMR spectra of the investigated phospha(V)zanes (III(a-c)). In addition, unconstrained geometry optimization of III(a-c) were carried out by means of DFT-B3LYP/3-21G(d) calculations to provide new insight into the structural parameters and molecular geometries of compounds III(a-c). The results are reported herein and compared with similar molecules whenever appropriate.     

Halogenated 7-deazapurine nucleosides: stereoselective synthesis and conformation of 2'-deoxy-2'-fluoro-beta-D-arabinonucleosides

The stereoselective syntheses of 5-halogenated 7-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine nucleosides 3b-d, 4a-c as well as 7-deaza-2'-deoxyisoguanosine are described. Nucleobase anion glycosylation of 2-amino-4-chloro-7H-pyrrolo[2,3-d]pyrimidine (5) with 3,5-di-O-benzoyl-2-deoxy-2-fluoro-alpha-D-arabinofuranosyl bromide (6) exclusively gave the beta-D-anomer, which was deblocked (--> 8), aminated at C4 (--> 3a) and selectively deaminated at C2 to yield 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl 7-deazaisoguanine (2). Condensation of the 5-halogenated 4-chloro-2-pivaloylamino-7H-pyrrolo[2,3-d]pyrimidines 9a-c with 6 furnished the N7-nucleosides 10a-c together with N2,N7-bisglycosylated compounds 11a-c. The former was converted to the corresponding 2,4-diamino-compounds 3b-d, and the latter was deblocked by NaOMe/MeOH to yield the 4-methoxy-nucleosides 4a-c. Conformational analysis of the sugar moiety of the nucleosides 2 and 3a-d was performed on the basis of vicinal [1H,1H] coupling constants. The fluorine atom in the sugar moiety shifts the sugar conformation from S towards N by about 10%, while the halogen substituents in the base moiety increase the hydrophobicity and polarizability of the nucleobases.     

Synthesis, structure and catalytic properties of CNN pincer palladium(II) and ruthenium(II) complexes with N-substituted-2-aminomethyl-6-phenylpyridines

N-substituted-2-aminomethyl-6-phenylpyridines 2a-c have been easily prepared from commercially available 6-bromo-2-picolinaldehyde in two steps. Reaction of 2a-c with PdCl(2) in toluene in the presence of triethylamine gave the CNN pincer Pd(II) complexes 3a-c in 18-28% yields. The CNN pincer Ru(II) complex 5 containing a Ru-NHR functionality could be obtained in a 71% yield by treatment of 2c with a Ru(II) precursor instead of PdCl(2). Additionally, the related CNN pincer Ru(II) complex 7 containing a Ru-NH(2) functionality has been synthesized by the reaction of 2-aminomethyl-6-phenylpyridine with the same Ru(II) precursor in a 68% yield. All the new compounds were characterized by elemental analysis (MS for ligands), (1)H, (13)C NMR, (31)P{(1)H} NMR (for Ru complexes) and IR spectra. Molecular structures of Pd complex 3c as well as Ru complexes 5 and 7 have been determined by X-ray single-crystal diffraction. The obtained Pd complexes 3a-c were effective catalysts for the allylation of aldehydes as well as for three-component allylation of aldehydes, arylamines and allyltributyltin and their activity was found to be much higher than a related NCN Pd(II) pincer in the allylation of aldehyde. On the other hand, the two new CNN pincer Ru(II) complexes 5 and 7 displayed excellent catalytic activity in the transfer hydrogenation of ketones in refluxing 2-propanol with the latter being much more active. The final TOF values were up to 4510 h(-1) with 0.01 mol% of 5 and 220,800 h(-1) with 0.005 mol% of 7, respectively.     

Novel 6-(trifiuoromethyl)cytosines and 6-(trifluoromethyl)uracils

Ethyl 3-amino-4,4,4-trifluorocrotonate ( 3 ) has been converted by a one step reaction with alkyl and aryl isocyanates to novel 3-substituted-6-(trifluoromethyI)uracils. Also several 3-amino-4,4,4-trifluorocrotonitriles ( 11a-c ) have been cyclized to novel 6-(trifluoromethyI)cytosines ( 13a-c ) and then hydrolyzed to the corresponding uracils ( 4, 14b-c ). Alkylation studies with isopropyl bromide of three 6-(trifluoromethyl)uracils ( 1, 4, 5 ) are described.     

Bridged cyclophosphazenes resulting from deprotonation reactions of cyclotriphophazenes bearing a P-NH group

Cyclotriphosphazene derivatives containing a P-NHR group in the side-chain react in the presence of a strong base to form stable intermolecular bridged products. Reaction of sodium hydride with mono-spiro cyclophosphazene derivatives having a P-NH group, N(3)P(3)Cl(4)[O(CH(2))(3)NH], (1a) or N(3)P(3)Cl(4)[CH(3)N(CH(2))(3)NH], (1b) leads to formation of bis-cyclophosphazenes bridged with an eight-membered cyclophosphazene ring in an ansa arrangement (2a, 2b) whereas reaction of sodium hydride with mono-amino cyclophosphazene derivatives [N(3)P(3)Cl(5)(NHR), R = n-hexyl, 3a; i-Pr, 3b; Ph, 3c] give bis-cyclophosphazenes bridged with a four-membered cyclophosphazane ring in a spiro arrangement (4a-c). In the latter reaction P-O-P bridged compounds (5a-c) were also obtained as a result of hydrolysis reactions associated with the amount of moisture in the solvent tetrahydrofuran. In addition, it was found that reaction of a mixture of cyclotriphosphazene with either mono spiro compound, (1a) or (1b), in the presence of sodium hydride lead to formation of the first examples of asymmetrically-bridged cyclophosphazenes (6a-b).     

Reactions of 2-aryl-4-methoxy-9-oxocyclohepta[b]pyrylium perchlorates with hydroxylamine and hydrazines

2-Aryl-4-methoxy-9-oxocyclohepta[b]pyrylium perchlorates 1a-c reacted with hydroxylamine hydrochloride and hydrazine sulfate in the presence of triethylamine to afford 2-aryl-4,9-dihydrocyclohepta[b]pyran-4,9-dione 4-oximes 3a-c and 4-hydrazones 4a-c in good yields, respectively. On the other hand, the reactions with methylhydrazine and phenylhydrazine gave respectively 1-methyl- and 1-phenyl-substituted 5-aryl-3-(3-tropolonyl)pyrazoles 5a-c and 6a-c in excellent yields. Treatment with 4-nitrophenylhydrazine gave 2-aryl-4,9-dihydrocyclohepta[b]pyran-4,9-dione 4-(4-nitrophenyl)hydrazones 7a-c in good yields.