Fast and efficient microwave-assisted synthesis of functionalized peptoids via Ugi reactions

A wide range of N-alkylglycines (peptoids) can be efficiently prepared via Ugi reactions using microwave irradiations. The results confirm the versatility and efficiency of the methodology for the preparation of functionalized peptoids. The products can be used in consecutive Ugi reactions to yield cyclic peptoids of potential biological interest.     

Dithioacetal as a 1,1-zwitterion synthon. Synthesis of functionalized alkenes by the coupling of benzylic dithioacetals with another 1,1-zwitterion synthon

Reaction of a dithioacetal sequentially with BuLi and alkyl bromide having an electron withdrawing substituent at the α-position followed by treatment with neutral alumina gives the corresponding olefination product in moderate to good yields.     

3,4-Diacetylhexane-2,5-dione—an effective synthon for synthesis of substituted azulene heteroanalogs by cyclocondensation reactions

The one-pot method for the synthesis of 4,8-dialkoxy-6-aryl-1,3-dimethylcyclohepta [c]furanium perchlorates has been developed. The method is based on the cyclocondensation of 3,4-diacetylhexane-2,5-diones with aromatic aldehydes and trialkyl orthoformates under the action of a 16% perchloric acid solution in acetic anhydride. Under similar conditions, with hydrogen sulfide, cyclohepta[c]thiophenium perchlorates have been obtained, while cyclohepta[c]pyrrolium perchlorates have been prepared with arylamines, ammonium acetate, or aliphatic amine acetates. A heteroanalog of azulene, 4,8-diethoxy-1,3-dimethyl-2-azaazulene, has been obtained for the first time. Hydrolysis of aza- and thiaazulenium salts gives the corresponding cyclohepta[c]pyrrol-4-ones and cyclohepta [c]thiophen-4-ones. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1596–1603, August, 1998.     

Water as an efficient medium for the synthesis of tetrahydro-β-carbolines via Pictet-Spengler reactions

A mild and efficient protocol for the Pictet-Spengler reaction in water using an acid catalyst has been described. The condensation of tryptophan, tryptamine, and N_b-benzyl tryptophan with different aldehydes having both electron-withdrawing and -donating substituents in the presence of a catalytic amount of TFA in water furnished tetrahydro-β-carbolines in good isolated yields. A salient feature of the water mediated Pictet-Spengler reaction was the general trend observed during the condensation of Trp-OMe and aryl/aliphatic aldehydes furnishing diastereomeric mixtures with a preference for the cis-isomer.     

Alum as an efficient catalyst for the multicomponent synthesis of functionalized piperidines

An effective approach to the synthesis of functionalized piperidines via a one-pot multicomponent reaction of aniline, β-ketoester and aldehyde in the presence of alum as an efficient catalyst has been reported. The present procedure offers advantages such as simple workup, short reaction time and offers rapid access to a variety of functionalized piperidines.     

Water as an efficient medium for the synthesis of functionalized enol ethers

Herein we report an efficient method for synthesis of β-alkylated and β,β-dialkylated α-iodo enol ethers in water. Radical addition in aqueous medium of ethyl iodoacetate, iodoacetonitrile, and iodoacetamide to ynol ethers leads to α-iodo enol ethers with moderate to excellent yields and high stereoselectivities.     

Ritter-type reactions of N-chlorosaccharin: a method for the electrophilic diamination of alkenes

[reaction: see text] N-Chlorosaccharin has been shown to undergo electrophilic Ritter-type reactions with alkenes in acetonitrile. The resulting labile beta-chloro sulfonylamidines can be ring-opened and cyclized to imidazolines. Overall this provides a one pot method for the electrophilic diamination of alkenes. Competing aziridine formation as well as allylic chlorination are also observed depending on the nature of the alkene used.     

Hetero Diels-Alder reactions of nitrosoamidines: an efficient method for the synthesis of functionalized guanidines

Hetero Diels-Alder reactions of transient nitrosoamidines are reported. Transient nitrosoamidines are formed by oxidation of protected N-hydroxylguanidines and are trapped in situ by 1,3-dienes to give [4 + 2] cycloadducts in good yields and regioselectivity. The resultant cycloadducts are versatile intermediates for the formation of functionalized guanidines. [reaction: see text]     

1,4-Difluoro-2,5-dimethoxybenzene as a precursor for iterative double benzyne-furan Diels-Alder reactions

[reaction: see text] The use of 1,4-difluoro-2,5-dimethoxybenzene as a novel precursor for iterative two-directional benzyne-furan Diels-Alder reactions, using a range of 2- and 3-substituted furans, is reported. Substituted oxabenzonorbornadienes were synthesized following the initial Diels-Alder reaction, which upon ring opening under acidic conditions gave substituted naphthol derivatives. Highly substituted anthracenols were generated in the second benzyne-furan Diels-Alder reaction following acid-catalyzed isomerization of the cycloadducts.     

Rapid and efficient synthesis of a fully functionalized synthon for the bottom half of the antiparasitic agent,ivermectin

The preparation of the bottom half of ivermectin 3 in 10 steps and 9% overall yield is reported.     

Sulfonic acid functionalized silica: an efficient heterogeneous catalyst for a three-component synthesis of 1,4-dihydropyridines under solvent-free conditions

Sulfonic acid functionalized silica catalyzed the three-component reaction of aromatic amines, alpha,beta-unsaturated aldehydes and beta-keto esters forming the corresponding 1,4-dihydropyridines in short reaction times and in high yields.     

Mild conditions for the synthesis of functionalized pyrrolidines via Pd-catalyzed carboamination reactions

[reaction: see text] The palladium-catalyzed carboamination of N-protected gamma-aminoalkenes with aryl bromides and triflates has been achieved under new, mild reaction conditions using the weak base Cs(2)CO(3) in dioxane solvent. These reactions tolerate a wide variety of functional groups, including enolizable ketones, nitro groups, methyl esters, and acetates, which are not compatible with previously described conditions.     

Sequential copper-catalyzed vinylation/cyclization: an efficient synthesis of functionalized oxazoles

A modular and practical synthesis of highly substituted oxazoles has been developed. The transformation consists of a sequential copper-catalyzed amidation of vinyl halides followed by cyclization promoted by iodine. A wide variety of functionalized oxazoles and polyazoles can be obtained in a selective manner from simple and easily accessible precursors.     

Stereoselective synthesis of cis-2,5-disubstituted pyrrolidines via Wacker-type aerobic oxidative cyclization of alkenes with tert-butanesulfinamide nucleophiles

Palladium(II)-catalyzed aerobic oxidative cyclization of alkenes with tethered tert-butanesulfinamides furnishes enantiopure 2,5-disubstituted pyrrolidines, originating from readily available and easily diversified starting materials. These reactions are the first reported examples of metal-catalyzed addition of sulfinamide nucleophiles to alkenes.     

Chiral 6-phenyl-2,3-bismethylenemethoxycarbonyl-[1,4]-dioxane as a designer synthon for an efficient and short synthesis of optically pure 2,6-dioxabicyclo[3.3.0]octane-3,7-dione

Chiral 6-phenyl-2,3-bismethylenemethoxycarbonyl-[1,4]-dioxane, synthesized by the PET cyclization of 8, has been used as a designer synthon for an efficient and short synthesis of optically pure 2,6-dioxabicyclo[3.3.0]octane-3,7-dione.     

Nicotinic acid functionalized organomodified silica as an efficient heterogeneous catalyst for the synthesis of benzoyl fumarate

A new hybrid catalyst has been developed by incorporating nicotinic acid onto an organomodified silica. The catalyst was applied as a heterogeneous catalyst for the synthesis of benzoyl fumarate. The reactions work well in the presence of 20 wt % of the catalyst at room temperature to produce the desired products in high yield. The catalyst could be recovered and reused without appreciable change in activity.     

A highly efficient In(OTf)3-catalyzed[3 + 3] annulation of spirocyclopropyl oxindoles with 1,4-di-thiane-2,5-diol

Spirooxindoles play an important role in drug discove ry and development.The development of efficient methods for the synthesis of spirooxindoles from easily available sta rting materials is of curre nt interest Herein,we report in detail the In(OTf)3-catalyzed[3+3]annulation of spirocyclopropyl oxindoles and 1,4-di-thiane-2,5-diol,which allows the facile preparation of spiro[indoline-3,4'-thiopyran]-2-ones bearing(tetrahydro)thiopyran skeleton.     

Lithiation of 1-alkynyl-1-chlorocyclopropanes and subsequent reactions with electrophilic reagents: synthesis of functionalized alkynyl- and vinylidenecyclopropanes

1-Alkynyl-1-chlorocyclopropanes undergo chlorine-lithium exchange on treatment with BuⁿLi in THF at -40—0 °C. Thus generated organolithium species react with carbon dioxide (dry ice) and acetone to give selectively hitherto unknown 1-alkynylcyclopropanecarboxylic acids and the corresponding alcohols in up to 74% yields. Similar reactions involving methyl chloroformate result in the mixtures of cyclopropylacetylenic and vinylidenecyclopropanic esters, while the use of aliphatic aldehydes as electrophiles provides secondary allenic alcohols in up to 64% yields.

     

An efficient regioselective synthesis of functionalized biphenyls via sequential reactions of aromatic aldehydes and β-keto esters or ketones

Knoevenagel/Michael/Aldol reactions of aromatic aldehydes and β-keto esters/ketones in a sequential manner yielded intermediate cyclohexanones in good yields. The latter, on oxidative aromatization with iodine, afforded functionalized biphenyls with at least one phenolic hydroxyl in moderate to good yields.