Synthesis of Indolines and Derivatives by Aza‐Heck Cyclization

For the first time, an aza‐Heck cyclization that allows the preparation of indoline scaffolds is described. Using N‐hydroxy anilines as electrophiles, which can be easily accessed from the corresponding nitroarenes, this method provides indolines bearing pendant functionality and complex ring topologies. Synthesis of challenging indolines, such as those bearing fully substituted carbon atoms at C2, is also possible using this method.     

由1,1-二溴烯烃一锅法合成1,4-二取代-1,2,3-三氮唑

以1,1-二溴乙烯和芳基叠氮化合物为原料,碘化亚铜为催化剂,室温下通过一锅法合成了1,4-二取代-1,2,3-三氮唑衍生物。考察了催化剂用量、反应溶剂、反应温度对产品收率的影响。通过IR,MS,_¹H NMR及_¹³C NMR等对目标产物结构进行确证,并提出了可能的反应机理。该合成方法具有环境友好、条件温和、操作简单、收率高等特点。     

Synthesis and Photochemistry of Novel 3,5-Diacetyl-1,4-dihydropyridines. II [1]

Summary. In continuation of previous work some novel 3,5-diacetyl-1,4-dihydropyridine derivatives were synthesized and their photochemical behavior was studied under oxygen and argon atmosphere. Oxidation of the dihydropyridine ring and formation of pyridine derivatives was the result of the reaction. The presence of oxygen affects not only on the rate of oxidation, but also the formation of some unidentified by-products was observed on irradiation under this atmosphere.     

Ready Access to 6-Alkyl, 6-Phenyl, 5,6-Dialkyl, and 5-Alkyl-6-phenyl Substituted 1,2,3,4-Tetrahydroisoquinolines

Summary.  Readily available bicyclic enone precursors were used in a novel strategy for the synthesis of 6-mono- and 5,6-disubstituted tetrahydroisoquinolines (alkyl and phenyl in position 6, hydrogen and methyl in position 5). After 1,2-addition of the respective organometallic reagents to the enones, the crude intermediate alcohols were subjected to a dehydratization/aromatization procedure using the in situ generated triphenylmethyl cation. Overall yields obtained by this procedure were between 27 and 86%. Whereas the synthesis of N-benzyl protected 6-t-butyl-tetrahydroisoquinoline was successful, partial dealkylation occurred in the 5-methyl-6-t-butyl analogue. Some of the new N-benzyl tetrahydroisoquinolines were transformed into the corresponding unprotected heterocycles. Received March 22, 2001. Accepted May 22, 2001     

One-Pot Synthesis of N-Substituted 4-Aryl-1,4-dihydropyridines Under Solvent-Free Conditions and Microwave Irradiation

Summary.  The three-component condensation of benzaldehyde derivatives, alkyl propiolates, and primary amines catalyzed by silica gel, zeolite HY, montmorillonite K-10, and acidic alumina under microwave irradiation gave N-substituted 4-aryl-1,4-dihydropyridines in short reaction times and high yields. The best results were obtained with silica gel. Received March 26, 2001. Accepted (revised) June 18, 2001     

Greener and Expeditious Synthesis of Fused Six-Membered N,N-Heterocycles Using Microwave Irradiation

The development of new strategies for the synthesis of fused heterocycles has remained a highly attractive but challenging proposition. An overview of the application of microwave irradiation in the synthesis of fused six-membered heterocyclic compounds containing two nitrogen atoms is presented, focusing on the developments in the past 5–10 years. This contribution covers the literature concerning the total synthesis of fused N,N-heterocycles.     

An Easy Synthesis of Pyranopyrimidines

Summary.  The one-pot reaction of valerolactone with nitriles in the presence of triflic anhydride affords 2,4-disubstituted pyrano[2,3-d]pyrimidines. Subsequent addition of methyl thiocyanate leads to 2,4-bis(methylthio)pyranopyrimidines which can easily be converted into the corresponding methylsulfonyl derivatives. The reaction of these derivatives with different nucleophiles produces a variety of substituted pyranopyrimidines.     

Catalyst-Free,One-Pot,Expeditious Synthesis of Aminoalkylnaphthols at Room Temperature

Aminoalkylnaphthols possess several biological and catalytic activities. A methodology has been developed for the multicomponent one-pot synthesis of aminoalkylnaphthols in dichloromethane under catalyst-free conditions at room temperature. The present approach possesses several advantages such as excellent yields, quick reaction time, mild reaction conditions, and very easy purification processes. Thirteen new compounds in addition to six known compounds have been synthesized by this methodology.     

An Expeditious Route for the Total Synthesis of Pondaplin Isolated from Annona glabra

A novel cyclic prenylated phenylpropanoid, pondaplin 1, was first synthesized in 26% overall yields through an expeditious route (7 steps) that employed highly regio- and stereoselective phenyltellurenylation to arylacetylene and palladium (Ⅱ) chloride-catalyzed carbonylation of hydroxy styryl phenyl telluride as key steps.     

An Expeditious Synthesis of Methyl Jasmonate

We present an efficient three‐step, two‐pot synthesis of methyl jasmonate (trans‐ 1 ) based on Diels–Alder cycloaddition of cyclopent‐2‐enone ( 2 ) and chloroprene (= 2‐chlorobuta‐1,3‐diene; 3d ) in either CHCl₃ or CH₂Cl₂, catalyzed by SnCl₄ (0.2 mol‐equiv.) at 20° (75% yield). Subsequent ozonolysis of a cis/trans 55 : 45 mixture of the cycloadduct 4d in either CH₂Cl₂ or AcOEt at ? 78°, followed by addition of Me₂S and MeOH in the presence of NaHCO₃, afforded, in 64% yield, a cis/trans 40 : 60 mixture of the known aldehyde 5c . The latter was reacted at ? 50° under salt‐free conditions with the propyl Wittig reactant to furnish 1 as a cis/trans 20 : 80 mixture ((E/Z) 3 : 97). Alternatively, a cis/trans 7 : 93 mixture ((E/Z) 4 : 96) was obtained in 88% yield from epimerized 5c (AcOH, H₂O, 40°; 99%) under usual Wittig conditions at ? 20°.     

Synthesis,antimicrobial and anticancer activities of some new N-methylsulphonyl and N-benzenesulphonyl-3-indolyl heterocycles: 1st Cancer Update

A series of 1-(N-methyl 2a–c and N-benzenesulphonyl-1H-indol-3-yl)-3-aryl-prop-2-ene-1-ones 3a–c were prepared and allowed to react with urea, thiourea or guanidine and gave the pyrimidine derivatives 4a–c to 9a–c. Base catalyzed reaction of 2a–c or 3a–c with ethyl acetoacetate gave cyclohexanone derivatives 10a–c and 11a–c, respectively. Reaction of the latter compounds with hydrazine hydrate afforded indazole derivatives 12a–c and 13a–c, respectively. On the other hand, condensation of 2c or 3c with some hydrazine derivatives namely, hydrazine hydrate, acetyl hydrazine, phenyl hydrazine and benzyl hydrazine hydrochloride gave pyrazole derivatives 14a,b-17a,b, respectively. Moreover, reaction of 2c or 3c with hydroxyl amine hydrochloride gave isoxazole derivatives 18a,b. The newly synthesized compounds were tested for their antimicrobial activity and showed that, compounds 14a, 14b, 15a and 15b were found to be the most active ones of all the tested compounds toward Salmonella typhimurium (ATCC 14,028) compared to the reference drug chloramphenicol. Eighteen new compounds namely, pyrimidin-2(1H)-ones 4a–c and 5a–c, pyrimidin-2(1H)-thiones 6a–c and 7a–c and pyrimidin-2-amines 8a–c and 9a–c were tested for their in vitro cytotoxicity against human liver carcinoma (HEPG2), human breast cancer (MCF7) and human colon cancer (HCT-116) cell lines and showed that, compounds 4c, 5c, 6c, 8c and 9c were found to be the highly active compounds compared to the reference drug doxorubicin.     

A High Yielding, One-Pot, Triton-B Catalyzed, Expeditious Synthesis of Carbamate Esters by Four Component Coupling Methodology

Summary. A novel process for the one-step chemoselective conversion of alkyl halides into carbamates as protected amines was developed using benzyltrimethylammonium hydroxide (Triton-B) in presence of gaseous carbon dioxide. Thus, carbamate esters of different amines were prepared in very good to excellent yields. Present address: Institute of Organic and Biomolecular Chemistry, George–August University, 37077, G?ttingen, Germany     

Nickel‐Catalyzed Asymmetric Reductive Heck Cyclization of Aryl Halides to Afford Indolines

A nickel‐catalyzed asymmetric reductive Heck reaction of aryl chlorides has been developed that affords substituted indolines with high enantioselectivity. Manganese powder is used as the terminal reductant with water as a proton source. Mechanistically, it is distinct from the palladium‐catalyzed process in that the nickel–carbon bond is converted into a C−H bond to release the product through protonation instead of hydride donation followed by C−H reductive elimination on Pd.     

Conventional and Microwave-Assisted Facile One-Pot Synthesis of N-Substituted Pyrrole-2,3,4,5-tetracarboxylates Under Neat Conditions

Highly substituted pyrroles 3a,f were prepared conveniently in a reaction of (dimethyl- and diethyl-)acethylenedicarboxylates 1a–b with N-(methyl- and aryl-) hydroxylamines 2a–d in the presence of NaHCO₃ using both conventional heating and microwave irradiation. Excelent yields of the very pure products were isolated under solvent-free conditions both at classical as well as microwave heating.     

An Efficient One-Pot Synthesis of N-Methoxy-N-methylamides from Carboxylic Acids

Abstract

Several N-methoxy-N-methylamides were prepared by the reaction of the corresponding carboxylic acids with N,O-dimethylhydroxylamine hydrochloride at room temperature using trichloromethyl chloroformate in the presence of triethylamine in excellent yields.     

An Efficient Microwave-Assisted Synthesis of Structurally Diverse Styrylquinolines

Summary. Aromatic aldehydes undergo condensation with quinaldines under microwave irradiation to afford structurally diverse styrylquinolines in high yields under solvent-free conditions. A comparison with the conventional method clearly indicates the advantages of the new protocol.     

Synthesis of 3,4‐Fused Tricyclic Indoles Using 3‐Alkylidene Indolines as Versatile Precursors

In this personal account, our recent studies of novel synthetic methods of 3,4‐fused tricyclic indole derivatives using 3‐alkylidene indoline derivatives as versatile precursors are discussed. Two types of cascade reactions producing 3,4‐fused tricyclic 3‐alkylidene indolines were developed based on a palladium‐catalyzed intramolecular Heck insertion to an allene‐allylic amination cascade and a platinum‐catalyzed intramolecular Friedel‐Crafts type C?H coupling‐allylic amination cascade. Furthermore, three types of 3,4‐fused tricyclic indoles were accessible from a single 3‐alkylidene indoline precursor via acid‐promoted olefin isomerization or oxidative treatments. The application of the developed methods to the synthesis of natural products bearing a 3,4‐fused tricyclic indole skeleton, (?)‐aurantioclavine, fargesine, and synthetic studies of dragmacidin E are also highlighted.     

The Reaction of Cyclic Nitroenamines with Isocyanates. Synthesis of 1,6-Polymethylene-6-nitromethyl-1,3,5-triazine-2,4-dione Derivatives

Summary. The reactions of cyclic nitroenamines with isocyanates were investigated. It was found that two different products could be obtained: in inert media -carbamoyl products were observed and when a strong base was used 1,6-polymethylene-6-nitromethyl-1,3,5-triazine-2,4-dione derivatives were isolated.