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.     

An efficient method for the phosphonation of C=X compounds

Reaction of trialkyl phosphites with C=X electrophiles (aldehydes, ketones, ketophosphonates, aldimines, ketimines, isocyanates, isothiocyanates, and activated olefins) in the presence of amines and anilines hydrohalides was studied. We found that pyridine hydrohalides effectively activate the reaction of tralkyl phosphites with various C=X electrophiles: aldehydes, ketones, ketophosphonates, aldimines, ketimines, isocyanates, isothiocyanates, and activated olefins. Particularly high activity showed pyridine hydroiodide. This reaction is a convenient method of synthesis of hydroxyphosphonates, aminophosphonates, carbamoylphosphonates, carbamoylthiophosphonates, and methylenebisphosphonates.     

An easy and general protocol for multicomponent coupling reactions of aldehydes, amides, and dienophiles

An improved procedure for the three-component coupling reaction of aldehydes, amides, and dienophiles (AAD-reaction) has been developed. The use of microwave technology enables the endo-selective synthesis of N-acyl cyclohexenylamines via condensation of readily available aldehydes and amides, and subsequent Diels-Alder reaction with electron-deficient dienophiles in significantly improved yields. Advantageously, there is no need of employing additional solvents and reaction times are drastically reduced compared to similar thermal reactions.     

Imino Diels-Alder reactions: One-pot synthesis of tetrahydroquinolines

<正>An efficient synthesis of tetrahydroquinoline derivatives is reported via three component coupling reactions of aldehydes and anilines with various dienophiles in the presence of a catalytic amount of perchloric acid adsorbed on silica gel(HClO_4-SiO_2) under mild reaction conditions.     

A novel four-component reaction for the synthesis of functionalised dihydropyrimidines

In a multi-component reaction (MCR) of a phosphonate, nitriles, aldehydes and isocyanates, N3-functionalised dihydropyrimidines can be synthesised efficiently via a Horner-Emmons/aza Diels-Alder pathway.     

Base-catalyzed Povarov reaction: an unusual [1,3] sigmatropic rearrangement to dihydropyrimidobenzimidazoles

A novel base-catalyzed Povarov reaction of arylamines, aldehydes, and electron-deficient dienophiles has been developed. An unprecedented in situ [1,3] sigmatropic rearrangement leading to 4,10-dihydropyrimido[1,2-a]benzimidazoles has also been discovered. An insight of the plausible mechanism is discussed and supported by X-ray crystal study. This cascade reaction is achieved in a one-pot multicomponent fashion on soluble support under microwave conditions.     

MgBr2‐Mediated Ionic Diels–Alder Reaction of Acetals of α,β‐Unsaturated Aldehydes and Ketones with 1,3‐Dienes

A facile, mild, and efficient methodology for the ionic Diels–Alder reaction of acetals of α,β‐unsaturated ketones and aldehydes as dienophiles with various 1,3‐dienes employing MgBr₂ as the Lewis acid catalyst to furnish corresponding Diels–Alder adducts at ambient temperature is described.     

Pyridinium perchlorate: A new catalyst for the reaction of trialkyl phosphites with the C=X electrophiles

Pyridinium perchlorate is an effective catalyst for the reaction of trialkyl phosphites with various C=X electrophiles: aldehydes, ketones, ketophosphonates, imines, isocyanates, isothiocyanates, and activated alkenes. The reaction leads to the formation of α-substituted phosphonates in a high yield. Advantages of the new catalyst are its high activity, availability, high product yields, and mild reaction conditions.     

One‐Pot synthesis of isothiachromene,isochromene, isoquinoline and tetrahydronaphthalene derivatives

A new series of tetrahydronaphthalene, isothiachromene, isochromene and isoquinoline derivatives were synthesized by reacting cyclohexylidenemalononitrile with active nitriles, active halo compounds, carbon disulfide, aldehydes, isothiocyanates and isocyanates, respectively.     

A multicomponent synthesis of triazinane diones

An efficient, one-pot synthetic protocol toward triazinane diones, a rather unexplored class of heterocyclic scaffolds combining phosphonates, nitriles, aldehydes, and isocyanates is described. The optimization of the reaction, synthesis of a small library of different triazinane diones, as well as alternative routes toward the triazinane dione scaffold are discussed.     

Rhenium-catalyzed synthesis of naphthalene derivatives via insertion of aldehydes into a C-H bond

A rhenium complex, [ReBr(CO)₃(THF)]₂, catalyzed reactions of aromatic ketimines and aldehydes with dienophiles, followed by dehydration, to give naphthalene derivatives in good to excellent yields. This reaction proceeds via C-H bond activation, insertion of an aldehyde, intramolecular nucleophilic cyclization, reductive elimination, elimination of aniline and Diels-Alder reaction. After dehydration, naphthalene derivatives were formed.     

Synthesis of perhydroxazin-4-ones. Competitive Mukaiyama versus hetero Diels–Alder reaction in the cycloaddition of 2-aza-3-trimethylsilyloxy-1,3-butadiene and aldehydes

The reactions of 2-aza-3-trimethylsilyloxy-1,3-butadiene with carbonyl dienophiles are described. 2-Aza-1,3-butadienes participate as dienes in the [4+2] cycloaddition with aldehydes to afford perhydroxazin-4-ones in good yields. Experimental results, however, show that a Mukaiyama type two-step reaction must be taken into account. The cycloadducts obtained have proved to be useful intermediates in the synthesis of α-amino-β-hydroxy acids.     

Iminium Ions as Dienophiles in Aza‐Diels–Alder Reactions: A Closer Look

This review highlights the state of the art of the use of iminium ions as dienophiles in Aza‐Diels–Alder (ADA) cycloadditions. An historical survey spanning the very first discovery of the reaction to modern developments, mechanistic studies and synthetic applications of the iminium variant of the ADA (iADA) reaction are presented. The discussion is focused on the intermolecular and intramolecular versions of the iADA reactions that are conducted in aqueous solutions to generate, in situ, the reactive dienophile from an amine hydrochloride and either aliphatic or aromatic aldehydes in the presence of a variety of dienes. The retro‐ADA reaction is also presented as an interesting method for the protection of amines. The use of Lewis acid catalysis in these reactions was thoroughly studied by the reactions of different amines and aldehydes conducted in the presence of lanthanide(III) complexes.     

Unsaturated aldehydes as alkene equivalents in the Diels-Alder reaction

A one-pot procedure is described for using alpha,beta-unsaturated aldehydes as olefin equivalents in the Diels-Alder reaction. The method combines the normal electron demand cycloaddition with aldehyde dienophiles and the rhodium-catalyzed decarbonylation of aldehydes to afford cyclohexenes with no electron-withdrawing substituents. In this way, the aldehyde group serves as a traceless control element to direct the cycloaddition reaction. The Diels-Alder reactions are performed in a diglyme solution in the presence of a catalytic amount of boron trifluoride etherate. Subsequent quenching of the Lewis acid, addition of 0.3% of [Rh(dppp)2Cl] and heating to reflux achieves the ensuing decarbonylation to afford the product cyclohexenes. Under these conditions, acrolein, crotonaldehyde and cinnamaldehyde have been reacted with a variety of 1,3-dienes to afford cyclohexenes in overall yields between 53 and 88%. In these transformations, the three aldehydes serve as equivalents of ethylene, propylene and styrene, respectively.     

Towards organo-click chemistry: development of organocatalytic multicomponent reactions through combinations of aldol, Wittig, Knoevenagel, Michael, Diels-Alder and Huisgen cycloaddition reactions

Here we report on our studies on combinations of amino acids and copper(I) for catalyzing multicomponent reactions (MCRs). We aimed to prepare both diene and dienophiles simultaneously, under very mild and environmentally friendly conditions, thus giving the constituents for a stereocontrolled Diels-Alder reaction, which in turn yields compounds 4 to 8. A diversity-oriented synthesis of polysubstituted spirotriones 4 to 6 were assembled from simple substrates like 1-(triphenylphosphanylidene)-propan-2-one, two aldehydes, and cyclic-1,3-diketones through Wittig/Knoevenagel/Diels-Alder and aldol/Knoevenagel/Diels-Alder reaction sequences in one pot under stereospecific organocatalysis. Chemical diversity libraries of polysubstituted spirotrione-1,2,3-traizoles 8 were assembled from simple substrates by means of Wittig/Knoevenagel/Diels-Alder/Huisgen cycloaddition reaction sequences in one pot under stereospecific organo/Cu(I) catalysis. Functionalized dispirolactones such as 6 are biologically active antioxidants and radical scavengers, and spirotrione-1,2,3-traizoles 8 have found wide applications in chemistry, biology, and materials science. Experimentally simple and environmentally friendly, organocatalytic, asymmetric four-component Diels-Alder (AFCDA) reactions of 1-(triphenylphosphanylidene)- propan-2-one, two different aldehydes, and cyclic-1,3-diketones produced diastereospecific and highly enantioselective substituted spirotriones 4 by means of a Wittig/Knoevenagel/Diels-Alder reaction sequence in one pot. Additionally we have developed an organocatalytic, asymmetric three-component Michael (ATCM) reaction of 1-(triphenylphosphanylidene)-propan-2-one, aldehyde, and cyclic-1,3-diketones that produced Michael adducts 15, 16 through a Wittig/Michael reaction sequence in a highly enantioselective one-pot process.     

Synthesis of enantiomerically pure cyclohex-2-en-1-ols: development of novel multicomponent reactions

Multicomponent reactions of aldehydes, dienophiles, and alcohols or carboxylic acid anhydrides have been developed for the first time. In situ generation of 1-acyloxy- and 1-alkoxy-1,3-butadiene derivatives in toluene in the presence of electron-deficient dienophiles provides selective and efficient access to functionalized cyclohex-2-ene-1-ols in good yields. Subsequent enzyme-catalyzed kinetic resolution gave the corresponding enantiomers with high enantioselectivity.     

Oxazaborolidinone-catalyzed enantioselective Diels-Alder reaction of acyclic alpha,beta-unsaturated ketones

allo-Threonine-derived O-acyl-B-phenyl-oxazaborolidinones are demonstrated to be powerful and highly enantioselective Lewis acid catalysts for the Diels-Alder reaction of simple acyclic enone dienophiles, expanding the scope of ketone dienophiles and dienes. With 10 to 20 mol % of catalyst, the Diels-Alder adducts are obtained in 76-98% ee with high endo-selectivity. The catalyst exhibits high activity for the reaction with the less reactive beta-substituted dienophiles and the less reactive 1,3-cycohexadiene and 1,3-butadiene derivatives. The application of the catalysts to the Diels-Alder reaction of furan is also described.     

Microwave-assisted traceless synthesis of hydantion-fused β-carboline scaffold

Multistep microwave-assisted reactions toward the synthesis of hydantoin-fused tricyclic tetrahydro-β-carbolines on the soluble polymer support have been developed. Polymer-bound tryptophan with various aldehydes has been subjected to Pictet-Spengler reaction to obtain tricyclic β-carboline conjugates. The terminal hydantoinyl moiety is constructed across polymer-bound β-carbolines by the reaction with various isocyanates under microwave irradiation to form urea intermediate. Simultaneous intramolecular cyclization of urea followed by cleavage of the polymer support leads to a traceless synthesis of tetracyclic scaffolds in high yield and high purity.     

New electronically enriched boronobutadienes for the synthesis of hydroxylated cyclohexenes via tandem [4+2]/allylboration

This communication describes the preparation and behavior of ether-substituted 1-boronobutadienes 1 and 2 in the Vaultier tandem [4+2]/allylboration three-component reaction involving electron-poor dienophiles and aldehydes. Whereas diene 1 failed to undergo the second, allylboration step of this process, diene 2 reacted with maleimides to give products 12, and even reacted with moderately activated dienophiles such as acrylates and acrylamide derivative 14 to provide a new stereoselective approach to the synthesis of hydroxyalkylated cyclohexene derivatives.