Intramolecular Diels-Alder reaction of 2-diphenylphosphinyl-5-(propargyloxymethyl)furans followed by nucleophilic 1,2-rearrangement of the phosphinyl group

The base-catalyzed intramolecular Diels-Alder reactions of 2-diphenylphosphinyl-5-(propargyloxymethyl)furans 2a-e gave the tetrahydrofuran ring annulated o-diphenylphosphinophenols 3a-e in 70-80% yields, a novel reaction involving an intramolecular Diels-Alder reaction of furan diene with allenyl ether dienophile followed by a nucleophilic 1,2-rearrangement of the diphenylphosphinyl group.     

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.     

Characterization of the switch in the mechanism of an intramolecular Diels-Alder reaction

Changing the dienophile moiety of an intramolecular Diels-Alder (IMDA) cycloaddition from an allyl ether to an allenyl ether can dramatically change the regioselectivity. We hereby show by density functional theory computations that such unprecedented divergence is produced by an underlying change in the mechanism of the reaction. The allyl ether yields a fused tetrahydrofuran through a classical Diels-Alder reaction, whereas the allenyl ether yields a (methylidene)tetrahydropyran through a stepwise process. The latter reaction involves an extreme asynchronism in the bond-forming events with a diradicaloid intermediate that is stabilized by conjugation and synergistic (captodative) effects. Comparison with intermolecular model D-A reactions, which are concerted processes with various degrees of asynchrony, helps explain the change in regioselectivity for the IMDA reaction of allyl systems and the shift in mechanism for the IMDA reaction of the allenyl derivatives studied.     

A novel intramolecular Diels-Alder cyclization involving indoloazepines

The reaction of indoloazepines 1 and α,β-unsaturated aldehydes in reflux toluene led to tetracyclic compounds 2. The key to this reaction was an intramolecular Diels-Alder cycloaddition by the indoloacrylate (dienophile)-dienamine (diene) intermediates generated in situ.     

Intramolecular Diels-Alder reactions using alpha-methylene lactones as dienophile

Several dienals were prepared and reacted in the presence of zinc metal with ethyl 2-bromomethylacrylate to provide in a Reformatsky-like reaction alpha-methylene lactones carrying a dienyl side chain. Thermolysis of these compounds (11, 21, 29, and 37) gave in an intramolecular Diels-Alder reaction the corresponding tricyclic cycloadducts (51, 52, 53, and 54). The cycloadditions took place with good diastereoselectivity and yields. The stereochemistry of the major isomer is in accordance with an endo transition state for cycloadducts 51, 52, and 54. In one instance (compound 58), the structure was supported by X-ray crystallography. In contrast to the other substrates, the nonatriene 29 cyclized to the exo product 53exo. The stereochemical situation could also be proven by NOESY NMR. However, the intramolecular Diels-Alder reaction did not work with furan as dienophile (compound 41) and substrate 50 featuring a densely functionalized tether connecting diene and alpha-methylene lactone.     

Syntheses of oxygenated spongiane diterpenes from carvone. Synthesis of dorisenone C

The synthesis of dorisenone C, a representative member of the spongiane-type diterpene family, is described. The synthesis follows a B→AB→ABC→ABCD approach and is based on the initial preparation of the previously known hydroxy-aldehyde 14 (AB rings) from R-(−)-carvone, followed by an intramolecular Diels-Alder reaction between an oxygenated diene moiety and an acetylenic dienophile for the construction of the C ring (compound 22), and adequate manipulation of the Diels-Alder adduct functionality for completion of the spongiane framework.     

Intramolecular diels-alder reaction by self-assembly of the components on a lewis acid template

Diels-Alder reactions of 2,4-hexadienol or its O-methyl ether with acrylate derivatives at 120 degrees C give mixtures of the four possible adducts with low selectivity. At ambient temperature and in the presence of Mg(II) or Al(III) Lewis acids, reactions of the dienol (but not the ether) are highly selective. Control experiments suggest that the Lewis acid serves both to tether the diene and dienophile and to induce an "intramolecular" reaction of the resulting "self-assembled" intermediate.     

An unusual intramolecular Diels-Alder reaction

The diene-ester (2) on heating undergoes an intramolecular Diels-Alder reaction via the intermediate (3). The β-alkyl furan moiety in 3 reacts as the dienophile adding to the cyclohexadiene unit to give 4.     

Total synthesis of epoxyquinols A, B, and C and epoxytwinol A and the reactivity of a 2H-pyran derivative as the diene component in the Diels-Alder reaction

Full details of two versions of the total synthesis of epoxyquinols A, B, and C and epoxytwinol A (RKB-3564D) are described. In the first-generation synthesis, the HfCl(4)-mediated diastereoselective Diels-Alder reaction of furan with Corey's chiral auxiliary has been developed. In the second-generation synthesis, a chromatography-free preparation of an iodolactone, by using acryloyl chloride as the dienophile in the Diels-Alder reaction of furan, and the lipase-mediated kinetic resolution of a cyclohexenol derivative have been developed. This second-generation synthesis is suitable for large-scale preparation. A biomimetic cascade reaction involving oxidation, 6pi-electrocyclization, and then Diels-Alder dimerization is the key reaction in the formation of the complex heptacyclic structure of epoxyquinols A, B, and C. Epoxytwinol A is synthesized by the cascade reaction composed of oxidation, 6pi-electrocyclization, and formal [4 + 4] cycloaddition reactions. A 2H-pyran, generated by oxidation/6pi-electrocyclization, acts as a good diene, reacting with several dienophiles to afford polycyclic compounds in one step. An azapentacyclic compound is synthesized by a similar cascade reaction composed of the four successive steps: oxidation, imine formation, 6pi-azaelectrocyclization, and Diels-Alder dimerization.     

Synthesis of novel heterocycles related to the dynemicin a ring skeleton

Studies directed towards the construction of the CDE ring framework of dynemycin A ( 1 ) are reported. A series of quinoline based dienophiles containing an activating group (e.g. 5 , Scheme 1), reacted with acyclic dienes (e.g. 4 , Scheme 1) in a Diels-Alder fashion under increased pressure to afford a variety of heterocyclic systems related to the CDE skeleton of dynemycin A. Reaction of dienophile 15 with cyclic diene 29 led to the novel hetereocycle 34 whereas attempted decarbonylation of 41 led to a novel rhodium-promoted intramolecular carbonylation of the terminal acetylene furnishing compound 43 .     

Expedient stereoselective synthesis of coronafacic acid through intramolecular Diels-Alder cyclization

A stereoselective synthesis of coronafacic acid, a natural component of the phytotoxin coronatin, was achieved using an intramolecular Diels-Alder reaction as the key step. The triene precursor bearing a substituted diene and a vinylketone as dienophile was synthesized and then tested in the thermal intramolecular cyclization. We have devised a new strategy to assemble the E,Z-diene through the stereoselective aldol reaction of an ester enolate followed by a stereoselective dehydration. Following the thermal cyclization, the corresponding hydrindanone thereby obtained with the desired relative stereochemistry could easily be converted into the natural product. The synthesis of the coronafacic acid was accomplished in six steps in 29% overall yield.     

Tandem intramolecular Diels–Alder/retro-Diels–Alder cycloaddition of 2H-chromen-2-one as dienes with the expulsion of CO_2

To study the intramolecular Diels-Alder cycloadditon of 2H-chromen-2-one as a diene, a series of chiral N-allyl-N-benzylamides that contain a 2H-chromen-2-one moiety were designed for the synthesis of benzo[f]isoindol-1-ones via an intramolecular Diels-Alder and a subsequent retro-Diels-Alder cycloaddition with the expulsion of CO₂. Both the yield (80%-89%) and absolute stereocontrol of the tandem reaction were high when an electron-withdrawing group was attached to the dienophile. The double bond in the styrene substructure remained in the products could be further derivatized by dihydroxylation.     

Poly-2-vinylfuran,synthesis, characterization,and diels-alder reaction with maleic anhydride

Poly-2-vinylfuran, synthesized by free-radical polymerization of 2-vinylfuran, was characterized by nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy. The pendant furan rings on the polymer backbone were then used as the diene component of a Diels-Alder reaction with maleic anhydride. The juxtaposition of the furan rings at first suggested an “avalanche” Diels-Alder reaction, in which the product of one cyclization would be the reactant of the next. A lack of polymer stereoregularity and the reversibility of the Diels-Alder reaction, however, prevented its formation. On the other hand, when the dienophile was used in a 1:1 molar ratio with respect to furan the smooth reaction produced a new polymer, the maleic anhydride adduct of poly-2-vinylfuran, which characterized by NMR and IR spectroscopy, was air stable and soluble in a number of solvents up to 70% transformation. When heated to 160°C the polymer reverted to maleic anhydride and somewhat decomposed poly-2-vinylfuran.     

Synthesis and Facile One-pot Aldol/Elimination/Diels-Alder Reaction of ß-Keto-Z-Dienylamides as Cytochalasin C Intermediates1

The coupling of chiral dienylamine 1ZE with ß-ketoesters and subsequent one-pot aldol reaction with derivatives of glyoxylic acid, acetylation of the hydroxyester thus produced, and intramolecular Diels-Alder reaction of the diene portion of the molecule with the incipient dienophile is described. The entire sequence generates all of the requisite chiral centers in the isoindolone skeleton of cytochalasin C simultaneously, in an overall yield of approximately 85%.     

Synthesis of Phenanthrene Derivatives by Intramolecular Cyclization Utilizing the [1,2]‐Phospha‐Brook Rearrangement Catalyzed by a Brønsted Base

The synthesis of functionalized phenanthrene derivatives was achieved by intramolecular cyclization utilizing the [1,2]‐phospha‐Brook rearrangement under Brønsted base catalysis. Treatment of biaryl compounds having an α‐ketoester moiety and an alkyne moiety at the 2 and 2′ positions, respectively, with diisopropyl phosphite in the presence of a catalytic amount of phosphazene base P2‐tBu provides 9,10‐disubstituted phenanthrene derivatives in high yields. This reaction involves the generation of an ester enolate through an umpolung process, that is, addition of diisopropyl phosphite to a keto moiety followed by the [1,2]‐phospha‐Brook rearrangement, the intramolecular addition to an alkyne, and the [3,3] rearrangement of the allylic phosphate moiety in a consecutive fashion.     

Complexation-Initiated Intramolecular Diels-Alder Reaction

A complexation-initiated intramolecular Diels-Alder reaction was demonstrated for the first time. On adsorbing the alkyne-Co(2)(CO)(6) complexes having a diene and a dienophile on opposite ends of the alkyne on silica gel, the Diels-Alder reaction was accelerated and the equilibrium was shifted toward the adduct formation to a greater extent compared to that in solution. Seven-membered ring formation was apparently favorable in this system.     

The diels-alder reaction of 5-aminopyrazole-4-carbonitrile with dmad: Synthesis and structural determination of dimethyl 2-(p-toluenesulfonylamino)-3-cyano-4-imino-1,4-dihydropyridine-5,6-dicarboxylate

The Diels-Alder reaction of 5-amino-1-(p-toluenesulfonyl)pyrazole-4-carbonitrile with dimethyl acetylenedi-carboxylate was carried out in the presence of potassium carbonate in dimethyl sulfoxide. The reaction gave dimethyl 2-(p-toluenesulfonylamino)-3-cyano-4-imino-1,4-dihydropyridine-5,6-dicarboxylate. The product was formed by transformation of the original Diels-Alder adduct followed by rearrangement of the p-toluenesul-fonylamino group into the 2-position of the pyridine ring. The structure of the product was irrefutably established by X-ray crystallography. This reaction is the first example of a pyrazole ring serving as the diene in a [4 + 2] cycloaddition reaction.     

Synthetic studies on the dienophile unit of methyl isosartortuoate. Part 2: SmI2-mediated 14-membered carbocyclization

The dienophile unit of methyl isosartortuoate has been synthesized. The 14-membered carbocycle was constructed by a SmI₂-mediated intramolecular Reformatsky reaction. The introduction of the oxo group at the γ-position of the α,β-unsaturated ester was achieved by rearrangement of an β,γ-epoxy ester.     

Hexabromocyclopentadiene V. The Diels-Alder reaction of hexabromocyclopentadiene

The reactivity of hexabromocyclopentadiene (1) as a diene in the Diels-Alder reaction has been determined with a number of dienophiles. The results of the present study show that 1 behaves as an electron-poor diene in that cyclopentadiene is a more reactive dienophile than maleic anhydride. Qualitatively, 1 has been found to be a less reactive diene than hexachlorocyclopentadiene. Several new Diels-Alder adducts of 5,5-dibromo-1,2,3,4-tetrachlorocyclopentadiene are also reported.     

First example of Diels-Alder reaction in the 2,3,4,4a-tetrahydroquinoline series. Synthesis of hydrogenated 5,8-ethanoquinolines

Diels-Alder reactions in the 2,3,4,4a-tetrahydroquinolines series were studied for the first time. It was shown that these dienes demonstrate only moderate reactivity. [4+2] Cycloaddition occurs stereo- and regioselectively only for alkenes bearing an electron-withdrawing group (acrylonitrile, maleic anhydride, dimethyl acetylene dicarboxylate, methyl propiolate). In this case, endo-Diels-Alder adducts, spiroannelated 5,8-ethanoquinolines, are formed in a high yield. Cyclopentadiene, being a highly reactive diene component, reacts with 2,3,4,4a-tetrahydroquinolines as the dienophile. Electron-rich unsaturated compounds (N-vinylpyrrolidone, vinylethyl ether, phenylacetylene) are inert to this cycloaddition reaction.