Domino Diels-Alder Reactions Research Articles

Efficient synthesis of polyfunctionalized carbazoles and pyrrolo[3,4-c]carbazoles via domino Diels-Alder reaction.

The p-TsOH-catalyzed Diels–Alder reaction of 3-(indol-3-yl)maleimides with chalcone in toluene at 60 °C afforded two diastereoisomers of tetrahydropyrrolo[3,4-c]carbazoles, which can be dehydrogenated by DDQ oxidation in acetonitrile at room temperature to give the aromatized pyrrolo[3,4-c]carbazoles in high yields. On the other hand, the one-pot reaction of 3-(indol-3-yl)-1,3-diphenylpropan-1-ones with chalcones or benzylideneacetone in acetonitrile in the presence of p-TsOH and DDQ resulted in polyfunctionalized carbazoles in satisfactory yields. The reaction mechanism included the DDQ oxidative dehydrogenation of 3-(indol-3-yl)-1,3-diphenylpropan-1-ones to the corresponding 3-vinylindoles, their acid-catalyzed Diels–Alder reaction and sequential aromatization process.

Recent Applications of the Diels–Alder Reaction in the Synthesis of Natural Products (2017–2020)

AbstractThe Diels–Alder reaction has long been established as an extremely useful procedure in the toolbox of natural product chemists. It tolerates a wide spectrum of building blocks of different complexity and degrees of derivatization, and enables the formation of six-membered rings with well-defined stereochemistry. In recent years, many total syntheses of natural products have been reported that rely, at some point, on the use of a [4+2]-cycloaddition step. Among classic approaches, several modifications of the Diels–Alder reaction, such as hetero-Diels–Alder reactions, dehydro-Diels–Alder reactions and domino-Diels–Alder reactions, have been employed to extend the scope of this process in the synthesis of natural products. Our short review covers applications of the Diels–Alder reaction in natural product syntheses between 2017 and 2020, as well as selected methodologies which are inspired by, or that can be used to access natural products.1 Introduction2 Syntheses from 20173 Syntheses from 20184 Syntheses from 20195 Syntheses from 20206 Conclusion

Diastereoselective Synthesis of Tetrahydrospiro[carbazole-1,3'-indolines] via an InBr3-Catalyzed Domino Diels-Alder Reaction.

A simple InBr3-catalyzed domino reaction of indoles, phenylacetylenes, and various 3-methyleneoxindolines in toluene is described. This reaction not only provided a convenient synthetic protocol for polysubstituted tetrahydrospiro[carbazole-1,3'-indolines] in good yields but also gave completely different diastereoisomers of the tetrahydrospiro[carbazole-1,3'-indolines] to that of the previously reported TfOH-catalyzed one-pot reaction of indoles, acetophenones, and 3-methyleneoxindolines. Additionally, the InBr3-catalyzed reaction of the initially prepared 1,1'-bis(indolyl)phenylethanes with 3-phenacylideneoxindolines also gave the corresponding tetrahydrospiro[carbazole-1,3'-indolines] in good yields and with excellent diastereoselectivity. The reaction mechanism involved the sequential in situ generation of reactive dienophilic 3-alkenylindole, the Diels-Alder reaction, and the Lewis acid controlled diastereoisomerization process.

Leo A. Paquette

Leo A. Paquette, 85, died on Jan. 21 in Columbus, Ohio. “Leo was a prolific organic chemist. His research contributions included heterocyclic chemistry, natural products synthesis, and properties of architecturally interesting compounds. I am particularly fond of his combination of domino Diels-Alder reactions and photochemistry to prepare the unsaturated hydrocarbon triquinacene. Leo is best known for the first synthesis of dodecahedrane, which also started with a domino Diels-Alder reaction. Leo was tireless in his service to the chemistry community—for example, on the editorial boards of Organic Syntheses and Organic Reactions.”—David J. Hart, friend and colleague Most recent title: Distinguished University Professor, Ohio State University Education: BS, chemistry, Holy Cross College, 1956; PhD, chemistry, Massachusetts Institute of Technology, 1959 Survivors: Wife, Estelle; son, Ron; daughters, Donna, Linda, Lisa, and Susan To recognize your late loved one or colleague, submit obituary information at ...

HOAc-Mediated Domino Diels-Alder Reaction for Synthesis of Spiro[cyclohexane-1,3'-indolines] in Ionic Liquid [Bmim]Br.

An efficient and diastereoselective synthetic protocol for the construction of spiro[cyclohexane-1,3′-indolin]-3-en-2′-ones and spiro[cyclohexane-1,2′-inden]-3-ene-1′,3′-diones was provided by HOAc-mediated domino reaction of pinacoles with typical dienophiles, such as 3-methyleneoxindolines and 2-arylideneindane-1,3-diones, in ionic liquid [Bmim]Br. This domino reaction involved the in situ generation of 1,3-dienes from acid-mediated dehydration of various pinacoles and the sequential Diels–Alder reaction.

Bidentate Lewis Acid Catalyzed Domino Diels-Alder Reaction of Phthalazine for the Synthesis of Bridged Oligocyclic Tetrahydronaphthalenes.

A domino process consisting of an inverse and a normal electron-demand Diels-Alder reaction is presented for the formation of bridged tri- and tetracyclic 1,2,3,4-tetrahydronaphthalenes catalyzed by a bidentate Lewis acid. The products were synthesized in a one-pot reaction from commercially available starting materials and contain up to six stereogenic centers. The tetrahydronaphthalenes were isolated as single diastereomers and are derivatives of phenylethylamine, which is well-known as a scaffold of amphetamine or dopamine.

Approaches to the total synthesis of chaetochalasin A

Chaetochalasin A is a complex natural product whose biosynthesis may involve two domino Diels-Alder reactions. Approaches to the total synthesis of chaetochalasin A using this approach have been studied. Methyl (6R,8S,2Z,4E,10E,12E,14E)-6,8,10,14-tetramethylhexadeca-2,4,10,12,14-pentaenoate was identified as a key intermediate and was synthesized from (E)-1-bromo-4-tert-butyldimethylsilyloxy-2-methylbut-2-ene using diastereoselective alkylations of derivatives of (+)-pseudoephedrine to introduce the stereogenic centres, a modified Julia reaction to prepare the conjugated triene and a phosphonate condensation to provide the (2Z)-alkene. However, during the synthesis, facile geometrical isomerisation of the (14E)-trisubstituted and (2Z)-double-bonds was observed and attempts to incorporate this pentaene into a synthesis of chaetochalasin A led to the formation of mixtures of products. The analogous ethyl 6,8,10,14-tetramethylhexadeca-4,10,12,14-tetraenoate [that lacks the (2Z)-double-bond] was incorporated into a Diels-Alder precursor by acylation of a valine-derived N-acylpyrrolidinone followed by oxidative elimination of the corresponding 3-(phenylselanyl)pyrrolidinone. However, preliminary studies of the macrocycle-forming Diels-Alder reaction for a synthesis of chaetochalasin A were complicated by (E,Z)-isomerisation of the (10E)-double-bond of the conjugated triene and three Diels-Alder adducts were isolated and characterised. Further studies of this approach to chaetochalasin A will require an alternative procedure for the generation of the acylpyrrolinone in the presence of the acid sensitive conjugated triene.

Domino Diels–Alder reactions of N-methoxyethyl-7-oxa-norbornadiene-2,3-dicarboximide: an elusive, highly reactive dienophile

Flash vacuum pyrolysis (FVP) has been used to generate the novel 7-oxa-norbornadiene-2,3-dicarboxylic imide that in situ gave an unprecedented cycloaddition reaction cascade with the imidofuran, a side-product of FVP. Stereoselectivity of cycloadditions was studied with the aid of density functional calculations, which fully support observed exo/ endo-selectivity.

Aromatic Fluorine as a Versatile Control Element for the Construction of Molecules with Helical Chirality

The p–p stacking and edge–face contacts between aromatic groups occupy prominent positions among noncovalent interactions, with helicity being one the most significant kinds of supramolecular organization driven by these interactions. Apart from stabilizing the structure of large molecules such as DNA, helicity has also been explored in the realm of synthetic small molecules. The so-called helicenes were originally developed merely as aesthetically pleasing molecules, however their unusual optical and electronic properties have attracted a great deal of attention of late. The chiral backbones of these molecules have given them roles in a variety of applications ranging from asymmetric catalysis to molecular motors and remote chirality sensors. Furthermore, the original helicene synthesis involving stilbene photocyclizations has evolved into more modern approaches, including various ring-closing methods such as domino Diels–Alder reactions, palladium-catalyzed arylations, cobalt-catalyzed cycloisomerizations of aromatic triynes, and ruthenium-catalyzed olefin metathesis. Despite these important advances, the synthesis of chiral helicenes is still tedious and requires considerable synthetic prowess. Due to their ability to undergo directional aggregation, helical molecules that are easy to prepare and modify are of considerable significance. Our group has been interested in versatile precursors to helically chiral molecules that would be amenable to regioand stereoselective structural alterations at a late stage of synthesis; molecules meeting these criteria are practically unknown. Herein we describe a methodology that allows us to generate several families of helically chiral compounds by straightforward intramolecular fluorine substitution. We have long been interested in molecules that contain aromatic fluorine. To the best of our knowledge, there are no reports on fluorine-containing helically chiral compounds apart from a few intriguing supramolecular perfluoroalkane helicates. Fluorine substitution is known to modulate aromatic/aromatic interactions by affecting the HOMO– LUMO gap, which leads to a strong propensity for the molecules to aggregate. Extended wave function delocalization in the resulting materials leads to high electron mobility, as observed upon going from pentacene to perfluoropentacene. The versatile 1,1’-binaphthalene2,2’-diol (binol, 1) skeleton was taken as a starting point for our purposes. The synthesis and applications of several fluorine-substituted binol analogues with various fluorination patterns have been developed by us and others previously. The act of fluorination causes significant perturbation in the electronic character of binol (Figure 1) with no substantial steric consequences.

First asymmetric synthesis of dihydrobenzo[c]phenanthrene-1,4-quinones with helical chirality

The first enantioselective synthesis of 12-tert-butyl substituted 7,8-dihydrobenzo[c]phenanthrene-1,4-quinones having helical chirality is achieved with good chemical and optical yields through a domino Diels–Alder reaction–sulfoxide elimination–oxidation process starting from enantiopure (S)-2-(p-tolylsulfinyl)-1,4-benzoquinone and 5-tert-butyl substituted 3-vinyl-1,2-dihydronaphthalenes as dienes.

Preparation of 9,9-dimethoxytetracyclo[8.5.0.0 2,8.0 7,11]pentadeca-3,5,12,14,-tetraene and conversion to hexacyclo[8.5.1.1 4,7.0 5,14.0 6,12.0 11,15.0 16,17]heptadeca-2,8-diene-13-one using a domino Diels-Alder reaction

The easily prepared bishomosecoheptaprismane ring system of 1 was converted to the tetracyclo[8.5.0.0 2,8.0 7,11]pentadeca-3,5,12,14-tetraene ring system of 10 using a photochemical decarbonylation/fragmentation reaction as the key step. The closely held face-to-face butadiene units in 10 undergo [4+4]cycloaddition under photochemical conditions and participate in domino Diels-Alder reactions with maleic anhydride and dicyanoacetylene. The maleic anhydride domino Diels-Alder adduct 18 was converted to the previously unreported hexacyclo[8.5.1.1 4,7.0 5,14.0 6,16.0 11,15.0 16,17]heptadecane ring system embodied in 19. A single crystal X-ray analysis of 20, one member of this new ring system, is reported and the results are compared with ab initio molecular orbital calculations.

A novel photochemical rearrangement of 1,3-diaryl-1,2-dihydropentalenes to the 1,5-isomers and their domino Diels-Alder reactions

Abstract Novel photochemical rearrangement of 1,3-diaryl-1,2-dihydropentalenes to 1,5-isomers and the subsequent domino Diels-Alder reactions of the latter with maleic anhydride are described. Synthesis, photorearrangement and subsequent domino Diels-Alder reactions of 1,3-diaryl-1,2-dihydropentalenes are described.

Domino Diels-Alder reactions. 6. Domino Diels-Alder cycloadditions to 9,10-dihydrofulvalene and 11,12-dihydrosesquifulvalene. A synthetic tool for the elaboration of polycondensed alicyclic systems

Domino Diels-Alder reactions. 6. Domino Diels-Alder cycloadditions to 9,10-dihydrofulvalene and 11,12-dihydrosesquifulvalene. A synthetic tool for the elaboration of polycondensed alicyclic systems

ChemInform Abstract: DOMINO DIELS‐ALDER REACTIONS. 4. C16‐HEXAQUINACENE

Chemischer InformationsdienstVolume 9, Issue 25 Isocyclic Compounds ChemInform Abstract: DOMINO DIELS-ALDER REACTIONS. 4. C16-HEXAQUINACENE L. A. PAQUETTE, L. A. PAQUETTESearch for more papers by this authorR. A. SNOW, R. A. SNOWSearch for more papers by this authorJ. L. MUTHARD, J. L. MUTHARDSearch for more papers by this authorT. CYNKOWSKI, T. CYNKOWSKISearch for more papers by this author L. A. PAQUETTE, L. A. PAQUETTESearch for more papers by this authorR. A. SNOW, R. A. SNOWSearch for more papers by this authorJ. L. MUTHARD, J. L. MUTHARDSearch for more papers by this authorT. CYNKOWSKI, T. CYNKOWSKISearch for more papers by this author First published: June 20, 1978 https://doi.org/10.1002/chin.197825142Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume9, Issue25June 20, 1978 RelatedInformation

Domino Diels-Alder reactions. I. Applications to the rapid construction of polyfused cyclopentanoid systems

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