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.     

[4+2] cycloaddition of intermediates generated from arynes and DMF

The trapping reaction of the transient intermediate ortho-quinone methides, generated by the insertion of arynes into a carbon–oxygen double bond of DMF, with dienophiles was investigated. The [4+2] cycloaddition products were obtained when the diesters of acetylenedicarboxylic acid were employed as dienophiles.     

不对称Diels-Alder反应

本文简要地讨论了各种Diels-Alder反应的不对称诱导方法。这些方法包括手性亲二烯体,手性二烯,以及手性Lewis酸的应用。     

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.     

A novel and facile stereocontrolled synthetic method for polyhydro-quinolines and pyridopyridazines via a diene-transmissive Diels-Alder reaction involving inverse electron-demand hetero Diels-Alder cycloaddition of cross-conjugated azatrienes

Cross-conjugated azatrienes bearing an electron-withdrawing sulfonyl or benzoyl group on the nitrogen atom underwent, on heating or in the presence of a Lewis acid (TMSOTf), an initial inverse electron-demand hetero Diels-Alder reaction with electron-rich dienophiles (vinyl ether, vinyl thioether, and allenyl ether) to produce 1:1 cycloadducts with high endo selectivity. The initial cycloadducts thus obtained underwent a second Diels-Alder reaction stereoselectively on the newly formed diene unit with electron-deficient dienophiles to give the crossed bis-cycloadducts, octahydroquinolines, with high diastereo-π-facial selectivity. The N-sulfonylazatrienes tethering an ortho-cinnamyloxyphenyl dienophile at the triene terminal underwent an initial intramolecular hetero Diels-Alder reaction of the inverse electron-demand type. The subsequent second Diels-Alder reaction of the formed mono-cycloadducts completed the diene-transmissive hetero Diels-Alder protocol to give benzopyrano[3,4-c]quinolines in a highly stereoselective manner.     

Applications of Dainshefsky's Dienes in the Asymmetric synthesis of Aza‐Diels‐Alder Reaction

Asymmetric hetero‐Diels‐Alder (AHDA) reactions provide a multitude of opportunities for the highly efficient, regio‐ and stereoselective construction of various heterocycles in enantiomerically pure form. The asymmetric aza‐Diels‐Alder (A‐aza‐DA) reaction using diversely hetero‐dienophiles and hetero‐dienes have been increasingly developed as a valuable method for the synthesis of functionalized nitrogen ring systems. The purpose of this review is to give a detailed discussion of the A‐aza‐DA reaction particularly, the stereoselective reactions of imines as dienophiles with Dainshefsky dienes to obtain optically pure aza‐Diels‐Alder products. The development of stereoselective variants of the reaction make use of imines as the dienophile and Dainshefsky dienes is at the forefront of these studies. This review updates the A‐aza‐DA reactions covering the literature from 1972 till date     

Simple and practical synthesis of pyrano- and furano[3,2-c]-quinoline derivatives under non-Lewis acid catalysis

One-pot synthesis of substituted pyrano- and furano[3,2-c]quinoline derivatives from appropriately substituted anilines, substituted benzaldehydes and dienophiles via Povarov reaction catalyzed by HCl-ethanol were reported.Good to excellent yields with high diastereoselectivity were obtained in all entries tested.     

Diels-Alder reaction in protic ionic liquids

Protic imidazolium ionic liquids have been tested as reaction media in the Diels-Alder reaction between cyclopentadiene and two dienophiles (dimethyl maleate and methyl acrylate). Good conversions and endo/exo selectivities were achieved. The activation of the dienophile by hydrogen bonding with protic imidazolium ILs was demonstrated.     

Regioselective synthesis of polysubstituted pyridines via hetero-Diels-Alder reaction of isotellurazoles with acetylenic dienophiles

Treatment of substituted isotellurazoles or their Te-oxides with acetylenic dienophiles efficiently afforded polysubstituted pyridine derivatives through a pathway involving hetero-Diels-Alder reaction of isotellurazoles and the subsequent tellurium extrusion from the intermediary cycloadducts.     

The Diels-Alder Reaction of Dienes Derived from Substituted 3-(Phenyl-Thio)-3-Sulfolenes

Substituted 3-(phenylthio)-3-sulfolenes (3) and (4) are good precursors for 2-(phenylthio)-1,3-butadienes (5) and (6). The Diels-Alder reaction of the dienes derived from (3) and (4) with various dienophiles was studied. It was found that heating of sulfolenes (3) with methyl propiolate and N-phenylmaleimide afforded the Diels-Alder adducts of (5) directly and with complete regio- and stereospecificity. The same reaction with methyl vinyl ketone gave a mixture of endo and exo addition products. If sulfolenes (3) were first converted to the dienes (5) using lithium aluminum hydride and then reacted with methyl vinyl ketone in the presence of anhydrous zinc chloride, the stereoselectivity could be improved. Sulfolenes (4) also underwent cycloreversion/cycloaddition with methyl acrylate, methyl vinyl ketone, and N-phenylmaleimide, but gave mostly the double bond-isomerized cycloaddition products. The regiochemistry of cycloaddition was delicately dependent on the dienophiles used.     

A novel Ireland-Claisen rearrangement/Diels-Alder tandem reaction of propargylic acrylates with acyclic dienophiles

A novel DABCO-catalyzed Ireland-Claisen rearrangement/Diels-Alder tandem reaction of propargylic acrylates 3 with dienophiles 4 was developed in the presence of an excess TMSCl and DBU with 1% hydroquinone as polymerization inhibitor in acetonitrile at refluxing temperature under air.This protocol gave cyclicα,β-unsaturated carboxylic acids 5 with complete regioselectivity.     

Synthesis and Diels-Alder reactions of α-fluoro- and α-trifluoromethylacrylonitriles

A novel synthetic method for the preparation of α-fluoro- and the still unknown α-trifluoromethylacrylonitriles is elaborated. The reaction of α-fluorovinylbromides and α-trifluoromethylvinylbromides with CuCN leads to the title compounds in good to high yields. While the α-fluoroacrylonitriles were isolated as mixture of Z/E-isomers, the α-trifluoromethylacrylonitriles were obtained as pure Z-isomers. The α-trifluoromethylacrylonitriles are shown to be excellent dienophiles for Diels-Alder reactions.     

One-pot synthesis of carbazoles from indoles via a metal free benzannulation

We report a simple, one-pot, and metal free benzannulation protocol to carbazoles starting with indoles, carbonyl compounds and an appropriate dienophiles. Mechanistically, this strategy generates an in situ diene by condensation between indole and carbonyl compound succeed and subsequent dehydration. Later, Diels–Alder reaction of this diene with a suitable dienophile followed by oxidation delivers the carbazole derivative. This methodology provide an easy access to carbazoles containing 1,4-naphthoquinone moiety.     

Entrapment of cyclopentadiene in zeolite NaY and its application for solvent-free Diels-Alder reactions in the nanosized confined environment

Nonpolar cyclopentadiene was stably entrapped as a monomer in the hydrophilic supercages of zeolite NaY. A monomer form of cyclopentadiene in the supercages was confirmed by ¹³C MAS NMR spectroscopy. The adsorbed cyclopentadiene in the confined cavities performed the Diels-Alder reaction with typical dienophiles under solvent-free conditions more effectively than in organic and water media.     

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.     

One‐Pot Synthesis of 2‐Arylthio‐2‐cyclohexenone Derivatives by the Diels–Alder Reaction of 4‐Arylthio‐3‐hydroxy‐2‐pyrones

The base‐catalyzed Diels–Alder reactions of 4‐arylthio‐3‐hydroxy‐2‐pyrones are reported. Treatment of 4‐arylthio‐3‐hydroxy‐2‐pyrones and dienophiles with triethylamine gave 2‐arylthio‐2‐cyclohexenone derivatives by the Diels–Alder reaction involving a decarboxylation in excellent to reasonable yields.     

The Synthesis of Naphthosultine and Benzodisultines and Their Pyrolysis with Dienophiles: Studies on o‐Naphthoquinodimethane and Bis‐o‐Quinodimethane

Sealed tube reactions of the naphthosultine 8 with a series of electron‐deficient dienophiles (fumaronitrile, N‐phenylmaleimide, dimethyl fumarate, and dimethyl acetylenedicarboxylate) in toluene at 180 °C gave corresponding 1:1 cycloadducts 11–14 in various amounts along with rearranged naphthosulfolene 7 in 67–95% yields. The reaction of 1,2,4,5‐tetra(bromomethyl)benzene with Rongalite (sodium form aldehyde sulfoxylate) and tetrabutylammonium bromide in DMF gave benzodisultines 17 and 18 in a combined yield of 56%. Sealed tube reactions of benzodisultines 17 and 18 with a series of dienophiles in xylene at 200 °C gave corresponding 1:1 and 1:2 cycloadducts 20–27 . The results suggested that thermal extrusion of sulfurdioxide from these sultines led to either o‐naphthoquinodimethane 6 (from 8 ) or bis‐o‐quinodimethane 19 (from 17 and 18 ); sub sequent trapping of these reactive intermediates by dienophiles and SO₂ gave various 1:1 and 1:2 Diels‐Alder ad ducts in modest to excellent yields.     

A novel MCR of isocyanates, aldehydes, and dienophiles

[reaction: see text] A novel one-pot procedure for the three-component coupling reaction of isocyanates, aldehydes, and dienophiles (IAD reaction) has been developed. Condensation of isocyanates and aldehydes and subsequent Diels-Alder reactions with electron-deficient dienophiles furnishes endo-selective amino-substituted cyclohexenes in good yield.     

Spirodialkylation of 3-(Phenylthio)-3-Sulfolene and Subsequent Synthetic Transformations

3-(Phenylthio)-3-sulfolene (1) underwent spirodialkylation to give products 2 which were desulfonylated to afford the dienes 3. The Diels-Alder reaction of 3 was achieved for some reactive dienophiles to yield spiro compounds. Compounds 2 were also converted to sulfonyldienes 9 which reacted as Michael acceptors.     

The Diels-Alder Reaction of 2,3-Disulfur-Substituted 1,3-Butadienes

The 2,3-disulfur-substituted 1,3-dienes (1) can be readily prepared from their stable 3-sulfolene precursors (2) by thermal extrusion of SO₂. The Diels-Alder reaction of diene (1) with several dienophiles has been studied. The substituent effect on the reactivity and regioselectivity follows the order of PhS >PhSO >PhSO₂. Lewis acid can greatly increase the regioselectivity of this reaction. The diene (1c), bearing a strong electron-withdrawing sulfonyl group, also reacted as a dienophile.