Selective synthesis of the two diastereomers of 5-oxo-1H-pyrrolizine-3-carboxylic acid

The rhodium catalysed reduction of a 2,5-disubstitued pyrrole 5 occurred selectively with the cis addition of hydrogen. The resulting cis-pyrrolidine was either cyclized without epimerization in refluxing toluene to the pyrrolizine 7 or with epimerization in refluxing acetic acid to the pyrrolizine 9 .     

Intramolecular capture of pummerer rearrangement intermediates. I. Synthesis of pyrrolo[2,1-c][1,4]benzothiazines

Treatment of 1-(2-alkylsulfinylphenyl)pyrroles with trifluoroacetic acid in refluxing toluene gives 4-substituted pyrrolo[2,1-c][1,4]benzothiazines in good yield when the alkyl group bears an electron withdrawing substituent on the α-carbon. In the absence of such a group, starting material is recovered. The sulfoxides are prepared by oxidation (mCBPA) of the corresponding sulfide. The sulfides are prepared from 2-aminobenzenethiol either by S-alkylation followed by conversion to the pyrrole using 1,4-dimethoxytetrahydrofuran in glacial acetic acid or by S-alkylation of 1-(2-phenylmercapto)pyrrole followed by oxidation to the sulfoxide.     

Solution- and solid-phase synthesis of 4-hydroxy-4,5-dihydroisoxazole derivatives from enantiomerically pure N-tosyl-2,3-aziridine alcohols

[reaction: see text] Enantiomerically pure N-tosyl-2,3-aziridine alcohols are directly converted into 4-hydroxy-4,5-dihydroisoxazole 2-oxides through oxidation to the corresponding aldehydes followed by in situ tandem nitroaldol-intramolecular cyclization. This study was concerned with (i) the selection of a suitable aziridine activation, (ii) the preparation of the target 4-hydroxy-4,5-dihydroisoxazole derivatives in solution, and (iii) the elaboration of a solid-phase process using hydroxy Merrifield-supported nitroacetic acid ester.     

Vicinal dianions of diethyl α-aroylsuccinates: preparation of functionalized-2,3-dihydrofurans and -furans, and diaxial 2,4-diaryl-3,7-dioxabicyclo[3.3.0]octanes

Vicinal dianions of diethyl α-aroylsuccinates react with aromatic aldehydes to provide functionalized 2,3-dihydrofurans as the major products together with γ-butyrolactones after treatment of the adducts obtained with a catalytic amount of p-toluenesulfonic acid in refluxing toluene. cis-2,3-Dihydrofurans are used as precursors for the preparation of tetrasubstituted furans and diaxial 2,4-diaryl-3,7-dioxabicyclo[3.3.0]octanes.     

A Novel Nitrone Cycloaddition/Rearrangement

Adamantanone-derived nitrone 4 and some other keto-nitrones, when reacted with aromatic and aliphatic aldehydes in refluxing toluene or tetrahydrofuran, formed the corresponding aldonitrones (Z)- 10 , the latter arising from the fragmentation of an initially formed 1 , 4 , 2 -dioxazolidine 6 to adamantan-2-one and an oxaziridine intermediate 11 , which then rearranges to (Z)- 10 .     

Silica gel assisted reductive cyclization of 2-nitro-β-piperidinostyrenes,derived from 2-nitrotoluenes,to indoles

An efficient modification of the Leimgruber-Batcho method of indole synthesis has been devised that facilitates the synthesis of a variety of 2,3-unsubstituted indoles containing halogen, methoxy and benzyloxy groups, from 2-nitrotoluenes, in high yields. The modified method involves the condensation of 2-nitrotoluenes with tripiperidinomethane followed by the reductive cyclization of the intermediate 2-nitro-β-piperidinostyrenes with iron and acetic acid in refluxing toluene in the presence of silica gel (column chromatography grade, 60–200 mesh).     

The chemistry of 2,3-dihydroisoxazole derivatives

Methods for the synthesis and transformations of 2,3-dihydroisoxazole derivatives are reviewed. Data on reduction and oxidation reactions and intramolecular rearrangements are generalized; their mechanisms are discussed.     

Studies on Thiazolopyridines. Part 1: Antimicrobial Activity of Some Novel Fluorinated Thiazolo[3,2-a]Pyridines and Thiazolo[2′,3′:1,6]Pyrido[2,3-d]Pyrimidines

Ternary condensation of aromatic aldehydes, malononitrile and thioglycolic acid (2:2:1 molar ratio) in ethanol/piperidine afforded the corresponding thiazolo[3,2-a]pyridines 1a-d . Thiazolo[2',3':1,6]pyrido[2,3-d]pyrimidine 4 was obtained by refluxing of compound 1a with acetic anhydride. Also, thiazolopyrido pyrimidine 6 was produced by refluxing of 1a with triethylorthoformate followed by treatment with hydrazine hydrate. Refluxing 1a with formic acid yielded the thiazolopyridopyrimidine 8 which on chlorination with thionyl chloride furnished the chloro derivative 9 . Finally, amino thiazolo[2',3':1,6]pyrido[2,3-d]pyrimidine 10 was obtained by treatment of 1a with formamide. The structures of these compounds were established on the basis of elemental analyses, IR, 1 H NMR, and mass spectral data. Also, the antimicrobial activity of some synthesized compounds is reported.     

四（烷硫基苯基）卟啉及其金属配合物的合成

某些人工合成的金属卟啉,由于其活化分子氧的功能,被广泛用作生物模拟氧化反应中的催化剂。金属四苯基卟啉及其衍生物是用得最普遍的模型化合物。文献中巳报道过各种四苯基卟啉衍生物的合成方法,但尚未见带烷硫基的四苯基卟啉衍生物的系统合成方法。本文报道这类四苯基卟啉衍生物及其金属配合物的合成。 本文采用通常的一步法合成四苯基卟啉衍生物,即首先参照文献方法合成烷硫基苯甲     

A new route to the synthesis of 4-amino-substituted pyrido[2,3-d]pyrimidin-5-one derivatives

The reaction of 6-(R-amino)-5-acetyl-4-methylsulfonyl-2-phenylpyrimidines with amines was studied. 6-Arylamino derivatives react with alkylamines to form 6-alkylamino-4-arylamino-5-acetyl-2-phenylpyrimidines, which upon refluxing in benzene with dimethylformamide dimethylacetal are converted to 4-alkylamino-8-aryl-2-phenylpyrido[2,3-d]pyrimidin-5(8H)-ones. The cyclization proceeds selectively with participation of the arylamino group only, the alkylamino group being not involved. At the same time, refluxing of 5-acetyl-4,6-dibenzylamino-2-phenylpyrimidine with dimethylformamide dimethylacetal in toluene affords the product of condensation on the acetyl group, which upon refluxing in o-xylene transforms to 4-benzylamino-8-benzyl-2-phenylpyrido[2,3-d]pyrimidin-5(8H)-one.

     

Thermal rearrangement of 1,3-thiazolidine sulfoxides: Thiolsulfinate and thioaldehyde intermediates

Stereospecific ring opening of the sulfoxides cis- 13 and trans- 14 in refluxing toluene gave the corre sponding sulfenic acids 9 , 10 intermediates respectively. The sulfenic acid 9 dimerized to the thiolsulfinate 17 by dual function of the sulfenic acid as S-nucleophile/S-electrophile with loss of water while the sulfenic acid 10 was unchanged. The stereospecific recyclization of 10 to the parent sulfoxide 14 increases the higher pi-electron density of the double. The thermolysis of the thiolsulfinate 17 gave the transient sulfenic acid 9 , which dimerized again to repeat the process and unisolable thioaldehyde 21 . The thioaldehyde 21 was con verted to either pyrrole 15 by the action of a sulfinic acid 20 catalyst formed inevitably by hydrolysis of 17 under the reaction conditions, or thiazole 18 under neutral conditions. In these rearrangements, the amide carbonyl group facilitated the elimination of a neighboring hydrogen.     

Chemistry of thienopyridines. XVII. Direct halogenation of thieno[2,3-b]pyridine

Thieno [2,3-b] pyridine (Ia) was converted into its 3-chloro, 3-bromo, and 3-iodo derivatives by means of elemental halogen, silver sulfate, and sulfuric acid. Bromine in a buffered chloroform solution of la also gave the 3-bromo compound (57% yield). Chlorine plus a refluxing mixture of Ia, chloroform, and water produced both the 3-chloro and the 2,3-dichloro derivatives. Various transformation products of these halothienopyridines (including the 2-nitro-3-halo compounds) are described and mass spectral fragmentation patterns are presented.     

Synthetic evaluation of an enantiopure tetrahydropyridine N-oxide. Synthesis of (+)-febrifugine

A study into the synthesis and synthetic utility of (S)-3-benzyloxy-3,4,5,6-tetrahydropyridine N-oxide is described. This nitrone is readily accessed from l-glutamic acid and the regio- and stereoselectivity of cycloaddition of this compound with a range of alkenes has been probed. Reductive cleavage of the major cycloadducts provides access to a diverse range of trans-2,3-disubstituted piperidines. The synthetic scope of this nitrone is further illustrated by the use of this compound as a key intermediate in a concise synthesis of the anti-malarial agent (+)-febrifugine.     

Macrolactones built from the bis-3,4(indol-1-yl)maleimide scaffold

15, 16, and 17-Membered lactones based on the bis-3,4(indol-1-yl)maleimide framework were obtained using intramolecular esterification reaction starting from 3-(1-ω-carboxyalkyl-2,3-dihydroindol-1-yl)-4-(1-ω-hydroxyalkyl-2,3-dihydroindol-1-yl)-maleimides. 3,4-Dibromo-maleimide, ω-(2,3-dihydroindol-3-yl)alkanoic acids, and ω-(2,3-dihydroindol-3-yl)alkanoles were used as starting compounds. Substitution of Br for the substituted indolines followed by the intramolecular cyclization of O-silylated hydroxyl acids derivatives led to macrolactones that incorporated 4-(dihydroindol-1-yl)-3-(indol-1-yl)maleimide moieties. Indoline nuclei in these compounds were dehydrogenated by DDQ in refluxing toluene to give 15, 16 or 17-membered lactones 3-[(ω-3-carboxyalkylindol-1-yl)-4-(ω-hydroxyalkylindol-1-yl)maleimides. Quantum chemical calculations showed that the formation of macrolactones of smaller size (13-membered) corresponds to the higher Gibbs energy ΔG^# and correlates with the absence of the target reaction product.     

Nitrone cycloadditions to 2,3-dihydro-1-phenyl-1H-phosphole 1-oxide. Double asymmetric induction and kinetic resolution by a chiral nitrone

The cycloadditions of nitrones with 2,3-dihydro-1-phenyl-1H-phosphole 1-oxide give a single cycloadduct deriving from a highly diastereoselective approach of the nitrone anti to the phenyl ring of phospholene oxide. When the chiral gliceraldehyde derived nitrone is used, only two diastereoisomers are produced in 1.7:1 ratio. The structural assignment based on NMR data and X-ray analysis of the major isomer established a trans C3–C4 stereochemistry (derived from endo TS with respect to nitrone) and a C3–C4′ relative stereochemistry of threo type in the major isomer and erythro in the minor one. Therefore, each enantiomer of phospholene oxide 6 gives exclusively one cycloadduct with five contiguous stereogenic centres in an established and predictable absolute configuration. The difference of reactivity of the two enantiomers allowed a partial kinetic resolution of the racemic phospholene oxide, affording (+)-(S) enantiomer with 90% enantiomeric excess.     

4,5-Unsubstituted 2,3-dihydroisoxazoles in the synthesis of racemic 4-substituted isoxazolidine-5-carbonitriles

The synthesis of novel types of the 4-hydroxy- and 4-bromosubstituted isoxazolidines is described. Dihydroxylation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles proceed from the less hindered side and provide the major 3,4-trans-isoxazolidine-4,5-diols in good yields. On the other hand, the hydroxybromination reaction of the model 3-phenyl-2,3-dihydroisoxazole predominantly proceeds with 3,4-cis selectivity. Isoxazolidine-5-carbonitriles have been prepared from isoxazolidines possessing a good leaving group at C5 by treatment with TMSCN in the presence of TMSOTf.     

一种新型α-甲醚基吡咯的合成

以乙酰乙酸苄酯(4)为原料, 经Knorr缩合制备了2,4-二甲基-3-丙酸甲酯基-5-羧酸苄酯基-1-氢吡咯 (2) 和2,4-二甲基-3-羧酸甲酯基-5-羧酸苄酯基-1-氢吡咯(3)。乙醚介质中,溴水氧化条件下,吡咯 (2) 发生自身缩合生成二吡咯甲烷 (7),吡咯 (3)无反应发生。在Pb(OAC)₄氧化条件下,当其浓度为吡咯 (3)浓度的2倍时,在80 ℃,吡咯 (3) 完全转华。所得产物经HCl甲醇溶液回流,以82%的产率制备了新型2-甲氧基甲基-3-羧酸甲酯基-4-甲基-5-羧酸苄酯基-1氢吡咯 (1)。吡咯(1)、(2)、(3)及二吡咯(7)的结构用核磁、元素分析、质谱和红外等测试技术进行了表征。吡咯(1)的构建对进一步研究吡咯构效关系具有一定参考价值。     

Dual reactivity pattern of allenolates "on water": the chemical basis for efficient allenolate-driven organocatalytic systems

A study of the reactivity pattern associated with zwitterionic allenolates "on water" is reported. This study establishes the chemical basis for two organocatalyzed allenolate-driven reaction networks operating "on water". The first one is a chemodifferentiating three building block (ABB') three-component reaction (ABB' 3CR) manifold comprising terminal alkynoates and aldehydes. The manifold produces propargylic enol ethers 3 with higher average efficiency than their homologues in organic solvents. The second one is a novel organocatalytic system elicited by the reaction of alkynoates and nitrones in the presence of tertiary amines or phosphines. While terminal alkynoates afford 2,3,5-trisubstituted 2,3-dihydroisoxazoles 5 and propargylic N-hydroxylamines 6, internal alkynoates selectively afford the 2,3,4,5-tetrasusbstituted 2,3-dihydroisoxazaole 10. Importantly, in both cases, the 2,3-dihydroisoxazole ring is obtained as a sole regioisomer.     

A convenient and general synthesis of 2-amino-1,3,4-thiadiazoles. Dehydration of acylthiosemicarbazides with methanesulfonic acid

2-Amino-5-alkyl and 2-amino-5-aryl-1,3,4-thiadiazoles were prepared by the dehydration of 2-acylthiosemicarbazides with molar equivalents of methanesulfonic acid in refluxing toluene. The synthesis appears to be general.     

Photolysis of (7R)-7-Methoxycarbonyl-1,5-di-f-butylbicyclo[2.2.2]oct-5-ene-2,3-dione at Various Temperatures

Upon irradiation at room temperature, the title compound 1 isomerized selectively and quantitatively into a cyclobutanedione 2 which underwent quantitatively bisdecarbonylation to afford a cyclohexadiene 3 . Thermolysis of 2 produced 1 and a bicyclo[2.2.1]heptenone 4 . Compound 4 was prepared in 70% yield by irradiation of 1 in refluxing dry toluene.