An efficient construction of bridged chiral tetracyclic indolidines, a core structure of asperparaline, via stereocontrolled catalytic Pauson-Khand reaction

A reaction of chiral enyne 22 derived from l-proline with a catalytic amount of cobalt (0) octacarbonyl in the presence of N-methylmorphorine N-oxide gave tricyclic enone 24 in 54% yield (73% based on consumed starting material). Treatment of enone 11 with aqueous methylamine followed by silica gel afforded bridged tetracyclic indolidine 1, a common structural motif of natural metabolites, an asperparaline series of compounds and also a potential intermediate for the synthesis of a paralytic alkaloid, asperparaline C (4), in 70% yield.     

A facile and efficient synthesis of enyne-reaction precursors by multicomponent reactions

Using improved reaction protocols for three-component coupling reactions of aldehydes, dienophiles, and amides (AAD-reaction) or anhydrides (ANAD-reaction) or orthoesters (ALAD-reaction), a variety of functionalized hexahydroisoindolo derivatives were synthesized and fully characterized. Condensation of ubiquitous available aldehydes with unsaturated amides or anhydrides or orthoesters and subsequent Diels-Alder reactions with electron deficient dienophiles furnishes endo-selective enyne-reaction precursors in good to excellent yield.     

New regio and stereoselective intermolecular Pauson-Khand reactions of allenamides

Intermolecular Pauson-Khand reactions are still quite limited in scope and yields. There are also few reports using allenes as the olefinic part in this version. We report herein new regio and stereoselective reactions of allenamides with several alkynes. These reactions give functionalized cyclopentenones bearing an exocyclic enamide, which can be useful synthetic intermediates.     

One-pot synthesis of α-acyloxyaminoamides via nitrones as imine surrogates in the Ugi MCR

α-acyloxyaminoamides can be prepared, with yields ranging from fair to very good (up to 89%), through an Ugi four component reaction by mixing a carbonyl component, a carboxylic acid, an isocyanide and an N-alkylated hydroxylamine in methanol. Preformed nitrones furnish the same final compounds with comparable yields.     

Modification and limitations of the Livinghouse catalytic Pauson-Khand reaction

The difficult and impractical purification of Co₂(CO)₈ is not necessary in the catalytic thermal Pauson-Khand reaction previously described by Livinghouse.     

Straightforward stereoselective synthesis of polyfunctionalised cyclohexenols using a multicomponent approach

An intramolecular Ugi 5-centre-4-component reaction (U-5C-4CR) followed by a palladium-catalysed ring-opening has been employed to transform oxabicycloheptene-based β-amino acids into two families of regioisomeric polyfunctionalised cyclohexenols. The whole process is completely stereoselective and enantiomerically pure products are obtained in high overall yields.     

Model studies toward a synthesis of asperaculin A: exploration of iterative intramolecular Pauson-Khand reaction based strategies to access the dioxa[5.5.5.6]fenestrane framework

A concise strategy, involving tandem intramolecular Pauson-Khand reactions (IPKRs) on a readily available ene-diyne precursor, to access the dioxa-fenestrane framework is delineated.     

Facile and efficient synthesis of a new class of bis(3′-indolyl)pyridine derivatives via one-pot multicomponent reactions

A series of 4-aryl-3,5-dicyano-2,6-di(3′-indolyl)pyridine derivatives were synthesized via a one-pot multicomponent reaction of aromatic aldehydes, 3-cyanoacetyl indoles, and ammonium acetate under microwave irradiation. Particularly valuable features of this method include high yields of products, broad substrate scope, short reaction time, and straightforward procedure.     

Design,stereoselective synthesis and computational calculations of novel hybrid compounds via Pauson-Khand reactions

A series of novel chiral hybrid compounds between benzofuran and bicyclic cyclopentenone and also benzothiophene and bicyclic cyclopentenone have been designed and synthesized. Chiral enynes derived from enantiomerically enriched homoallyl and homopropargyl alcohols were converted into bicyclic cyclopentenone structures by intramolecular Pauson-Khand reactions. This strategy provides a facile access to various bicyclic cyclopentenones substituted with benzofuran or benzothiophene ring systems in good yields. In addition to the experimental work, the ground state geometries of the hybrid compounds were optimized using Density Functional Theory applications at the B3LYP/6-31G(d,p) level in order to obtain information about the 3D geometries and electronic structure.     

Microwave-mediated one step synthesis of tri- and tetracyclic heterocyclic molecules

Abstract

Tricyclic and tetracyclic compounds related to vasicine and batracyclin, respectively, have been synthesized via condensation of dicarboxylic acids (aliphatic acid, homophthalic acid, and aromatic acid) with diamines (aliphatic, aminobenzyl amine, and aromatic amine) under solvent-free condition.     

Domino 6pi-electrocyclization/Diels-Alder reactions on 1,6-disubstituted (E,Z,E)-1,3,5-hexatrienes: versatile access to highly substituted tri- and tetracyclic systems

The (E,Z,E)-1,3,5-hexatrienes 1a, 2a,b and 3b undergo 6pi-electrocyclization within 15-30 min upon heating to 200-215 degrees C. While the cyclohexene-annelated products 8a,b were stable, the analogous cyclopentene- and cycloheptene-annelated derivatives 7a and 9b easily underwent dehydrogenation to the corresponding aromatic compounds 10a and 12b during the work-up. The cyclohexadiene derivatives 8a,b were employed in thermal Diels-Alder reactions with 4-phenyl-3H-1,2,4-triazoline-3,5-dione (PTAD) and tetracyanoethylene (TCNE) to give the expected [4+2] cycloadducts 13a and 14a in good yields (60 and 78%). The initially formed cycloadduct of 8a and dimethyl acetylenedicarboxylate (DMAD) underwent a subsequent retro-Diels-Alder reaction to give the tetrahydronaphthalene 11b (47%). Under high pressure (10 kbar), the cycloadduct 15a was formed at room temperature and could be isolated in 44% yield. TCNE and N-phenylmaleimide with 8a under high pressure also led to the [4+2] cycloadducts 14a and 16a in good yields (60 and 77%). The 6pi-electrocyclization and subsequent Diels-Alder reaction, when performed as a one-pot domino process, provided direct access to Diels-Alder products of intermediately formed 6pi-electrocyclization products, for example from the 1,3,5-hexatrienes 1a,b, 2a,b, 3b and TCNE to the corresponding tricyclic products 17a,b, 14a,b, 18b in moderate to good yields (27-80%) depending on the nature of the alkoxycarbonyl group. Such sequential reactions with N-phenylmaleimide, maleic anhydride, dimethyl maleate and fumarodinitrile, the latter two under high pressure (10 kbar), worked as well to yield 16b (70%), 19a,b (19, 32%) and 20b (39%) and 21b (76%), respectively. With PTAD, however, the hexatrienes 2a,b reacted at ambient temperature without 6pi-electrocyclization to give the formal [4+2] cycloadducts 27a,b (48 and 46%), most probably via zwitterionic intermediates 23a,b and 25a,b.     

Acid-mediated synthesis of fully substituted 1,2,3-triazoles: multicomponent coupling reactions,mechanistic study,synthesis of serine hydrolase inhibitor and its derivatives

We describe the full details of multicomponent coupling reactions in acid-mediated synthesis of fully substituted 1,2,3-triazoles syntheses, and their applications to bioactive molecule synthesis. For substitution with wide range of nucleophiles, selection of acids or activating reagents was important, and various types of multicomponent coupling reactions were demonstrated, allowing functionalization with alcohols, amines, thiol, azide, and carbon nucleophiles. Four-component couplings including double triazolations were also tested. The efficiency of this method was demonstrated by the synthesis of serine hydrolase inhibitor and its novel substituted derivatives.     

Straightforward access to 2-iminoisoindolines via three-component coupling of arynes, isocyanides and imines

A three-component coupling reaction of arynes, isocyanides and N-tosylaldimines has been developed to offer modest to high yields of diverse 2-iminoisoindolines in one step. Intermediacy of arynes in the coupling has been verified by the reaction of unsymmetrical arynes.     

An efficient synthesis of benzodiazepine derivatives via a one-pot,three-component reaction accelerated by a chitosan-supported superparamagnetic iron oxide nanocomposite

This work describes the catalytic ability of Fe₃O₄@chitosan as an environmentally benign and stable composite nanocatalyst for the synthesis of benzodiazepine derivatives starting from o-phenylenediamine, dimedone, and different aldehydes via a one-pot, three-component reaction at room temperature. High-to-excellent yields, easy work-up, reusability of the nanocatalyst, and non-toxicity are some of the advantages of this protocol.     

One-pot synthesis of substituted indolines via a copper-catalyzed sequential multicomponent/C-N coupling reaction

One-pot synthesis of 2-(N-sulfonylimino)indolines has been developed. The procedure combines the copper-catalyzed three-component reaction of sulfonyl azides, o-bromophenylacetylenes, and amines and the copper-catalyzed intramolecular C-N coupling in one sequence, which afforded the products in moderate to good yields. The resulting 2-(N-sulfonylimino)indolines could be easily transformed to pharmaceutically valuable oxindoles (indolin-2-ones).     

One-pot and catalyst-free synthesis of thiosemicarbazones via multicomponent coupling reactions

A novel and efficient procedure for the synthesis of thiosemicarbazones has been achieved via a multicomponent and catalyst-free reaction of phenyl or p-chlorophenyl isothiocyanate, hydrazine, and aldehydes or ketones. The method afforded 20 thiosemicarbazones in good yields and short reaction time.     

Multicomponent reactions for the synthesis of new 3′-indolyl substituted heterocycles under microwave irradiation

A series of polysubstituted (3′-indolyl)pyrazolo[3,4-b]pyridine and (3′-indolyl)benzo[h]quinoline derivatives were synthesized via one-pot multicomponent reactions of aldehydes, 3-cyanoacetyl indoles with 5-aminopyrazol or naphthylamine under microwave irradiation. Particularly valuable features of this method include high yields of products, broad substrate scope, short reaction time and straightforward procedure.