Bismuth nitrate-catalyzed multicomponent reaction for efficient and one-pot synthesis of densely functionalized piperidine scaffolds at room temperature

A simple, straightforward, and highly efficient diastereoselective multicomponent one-pot synthesis of a series of pharmaceutically interesting functionalized piperidine derivatives has been developed based on a low-cost and environmentally benign Bi(NO₃)₃·5H₂O catalyst via tandem reactions of 1,3-dicarbonyl compounds, aromatic aldehydes, and various amines in ethanol at room temperature. High atom-economy, good yields, eco-friendliness, and mild reaction conditions are some of the important features of this protocol.     

Cyanuric chloride catalyzed metal-free mild protocol for the synthesis of highly functionalized tetrahydropyridines

An environmentally benign, facile and elegant synthetic approach for the convenient access of a series of diverse 2,6-diaryl-tetrahydropyridine-3-carboxylates via a one-pot, pseudo five-component condensation of ethyl acetoacetate, anilines and aromatic aldehydes under mild reaction conditions has been described. This domino strategy allows rapid cyclization in the presence of 10 mol% of cyanuric chloride as a source of hydrochloric acid to afford the desired target skeletons in excellent yields. The present protocol offers prominent advantages of simple operational procedure, metal-free organocatalyst, practically robust and extensive substrate scope.     

Multicomponent synthesis of dihydropyridines catalyzed by L-proline

Multicomponent synthesis of mono and bis 4-substituted-1,4-dihydropyridines from aldehydes,dimedone and ammonium acetate in the presence of an efficient recyclable catalyst,L-proline,in high yield and short reaction time is reported.     

Trifluoroborane catalyzed chemoselective synthesis of highly functionalized 1,3-thiazin-2-ylidenes

An efficient chemoselective synthesis of 1,3-thiazine-2-ylidenes was achieved via annulations of β-aroyl-thioacetamide with propargyl alcohols using BF₃ OEt₂ as Lewis acid catalyst. A broad spectrum of substrates was well tolerated under the mild reaction conditions producing desired thiazine heterocyclics in good yields.     

Enatioselective organocatalytic synthesis of highly functionalized tetrahydrothiophenes by a Michael-aldol cascade reaction

A catalytic asymmetric Michael-aldol cascade process for efficient synthesis of trisubstituted tetrahydrothiophenes is reported with high enantio- and diastereo-selectivities. Notably, three consecutive stereogenic centers including one chiral quaternary carbon center are efficiently created in the ‘one-pot’ operation.     

吗啉催化的串联反应合成多取代环己酮（英文稿）

本文以吗啉为催化剂,活泼亚甲基化合物与芳香醛发生串联反应,以最高90%的产率得到了系列多取代的环己酮。反应经历了Knoevenagel缩合、Michael加成、Aldol反应等系列过程。吗啉作为有机分子催化剂,在串联过程中通过亚胺离子活化及烯胺活化羰基化合物而发挥重要作用。合成的环己酮可通过已知方法进一步转化为2-环己烯酮。本方法具有简便、易操作和绿色的特点。     

Efficient synthesis of highly functionalized tetrahydropyridopyrimidines by a novel three-component coupling reaction

We report the development of a novel three-component coupling reaction (3CC) for the synthesis of alkoxy tetrahydropyridopyrimidines. Systematic optimization of reaction parameters identified 3CC conditions tolerant of a wide array of functionality at all three sites of diversity, providing densely functionalized products in moderate to excellent yields. The newly developed chemistry has since been applied to the lead optimization process on a novel drug discovery program, facilitating rapid compound advancement.     

Multicomponent assembly strategies for the synthesis of diverse tetrahydroisoquinoline scaffolds

Several novel multicomponent assembly processes have been developed for the rapid and efficient assembly of various heterocyclic scaffolds bearing a tetrahydroisoquinoline core, each of which allows for facile derivatization to access a diverse array of compounds. This work led to the serendipitous discovery of a new method for the synthesis of a fused quinazolone ring system, which was applied to a one-step total synthesis of the quinazolinocarboline alkaloid rutaecarpine.     

Three-component domino reaction synthesis of highly functionalized bicyclic pyrrole derivatives

An efficient one-pot synthesis of highly functionalized bicyclic pyrrole derivatives by a three-component domino reaction of heterocyclic ketene aminals (HKAs), arylglyoxal monohydrate, and indoles in ethanol medium catalyzed by acetic acid is described. In this procedure, three sigma bonds were formed simultaneously. The present synthesis features excellent regio-selectivity, easy purification as well as simple starting materials.     

Facile one-pot synthesis of novel highly functionalized dihydro-1H-pyrrole derivatives catalyzed by molecular iodine

An efficient, environmentally benign and molecular iodine promoted protocol was described for cascade synthesis of two kinds of novel dihydro-1H-pyrrole derivatives, 5 and 7. Compounds 5 were prepared via four-component reaction between diethyl acetylenedicarboxylate (DEAD), aromatic amines and phenylglyoxal monohydrate catalyzed by 10 mol% of iodine in ethanol at room temperature. In addition, using same reaction conditions, a three-component reaction between (E)-N-methyl-1-(methylthio)-2-nitroethenamine (NMSM), aromatic amines and arylglyoxal monohydrate was performed to access product 7. These transformations apparently proceed through an imine intermediate followed by iodine induced Mannich reaction and subsequent intra-molecular cyclization sequences. The protocol involves the formation of CN, CC and OH bonds leading to the preparation of a hexa substituted five membered ring with two stereo centres. The syntheses avoid the use of traditional column chromatography and recrystallization purification methods and, hence, follow the group-assisted purification (GAP) chemistry process.     

Phosphine-catalyzed domino reaction: an efficient method for the synthesis of highly functionalized spirooxazolines

A novel phosphine-catalyzed intermolecular [3 + 2] cycloaddition of ynones and N-substituted isatins was developed. In this reaction, substituted ynones, serving as a C(3) synthon, were successfully applied in intermolecular annulation reactions. A number of functionalized spirooxazolines were obtained in high yields and stereoselectivity.     

A novel one-pot synthesis of highly diverse indole scaffolds by the Ugi/Heck reaction

A novel one-pot two-step multi component reaction of acrylic aldehydes, bromoanilines, acids and isocyanides yielding polysubstituted indoles is described. The reaction is based on the combination of an Ugi four-component reaction followed by an intramolecular Heck-reaction. The simultaneous use of formic acid and cinnamaldehydes affords in situ generation of 1H-indoles. Convertible isocyanides can also be used with success in this Ugi/Heck strategy and enable synthesis of 1H-indole-2-carboxylic acid building blocks.     

An efficient synthesis of highly functionalized [5,6] aromatic spiroketals by hetero-Diels-Alder reaction

A hetero-Diels-Alder reaction of vinyl sulfoxides with o-quinone methides precursor constructs highly functionalized [5,6] aromatic spiroketal skeletons in moderate to good yields with high regioselectivity. The two functional groups (ketone and olefin) can be further subjected to many synthetic transformations.     

Tandem Michael addition/ylide olefination reaction for the synthesis of highly functionalized cyclohexadiene derivatives

A tandem Michael addition/ylide olefination for the rapid creation of highly functionalized cyclohexadiene is developed. The tandem annulation reactions afford versatile cyclohexadienes in good to excellent isolated yields. This method has been successfully applied to the synthesis of three biologically active molecules.     

DABCO catalyzed facile synthesis of highly functionalized pyrazolines from Baylis-Hillman acetates and ethyl diazoacetate

A convenient synthesis of pyrazolines is reported via DABCO mediated reaction of ethyl diazoacetate (EDA) with Baylis-Hillman acetates. The products were obtained in good to excellent yields (70-95%).     

Convergent synthesis of functionalized fluoroallylamines by the Julia-Kocienski reaction

The synthesis of β-fluoroallylamines is reported from aminofluorobenzothiazolylsulfones. These open a new route for a short synthesis of vinylic fluoride containing highly functionalized amino residues.     

Facile synthesis of highly functionalized ethyltrifluoroborates

Organotrifluoroborates are generating increased interest because of their ease of preparation and purification and indefinite shelf life. Herein we report the preparation of organotrifluoroborates bearing functional groups that can be manipulated at different stages of the synthetic route, exploiting the inertness of their carbon-boron bonds. The alkylation of 2,2-dicyanoethyltrifluoroborate with a variety of electrophiles and of (EWG)2CH2 with potassium iodomethyltrifluoroborate resulted in di- and trisubstituted ethyltrifluoroborates in good to excellent yields.     

Phosphine-catalyzed synthesis of highly functionalized coumarins

2-Styrenyl allenoates are converted into cyclopentene-fused dihydrocoumarins through phosphine-catalyzed regio- and diastereoselective [3 + 2] cycloadditions. Remarkably, changing the solvent from THF to benzene promotes the conversion of the 2-(2-nitrostyrenyl) allenoate into a tricyclic nitronate through a previously undocumented mode of phosphine catalysis. This nitronate was subjected to efficient face-, regio-, and exo-selective 1,3-dipolar cycloadditions to provide tetracyclic coumarin derivatives.     

Asymmetric synthesis of functionalized piperidine derivatives: synthesis of (S)-anatabine

A short and efficient chiral synthesis of 6-aryl-5-phenylsulfonyl-1,2,5,6-tetrahydropyridines was achieved in moderate yield and with good selectivity. The absolute configurations were assigned by extending the methodology to (S)-anatabine and as well with NMR experiments.