Intramolecular Diels-Alder Reaction of Furans with Allenyl Ethers Followed by Phenylthio and Trialkylsilyl Groups Rearrangement

A new reaction involving an intramolecular Diels-Alder reaction of a furan diene with an allenyl ether dienophile followed by phenylthio group rearrangement was discovered. Treatment of the propargyl ethers 2a-c with t-BuOK in t-BuOH at 85 ° C gave the phenylthio group rearrangement products 5a-c and 6a-c . A reaction involving an intramolecular Diels-Alder reaction of a furan diene with an allenyl ether dienophile followed by trialkylsilyl group rearrangement is also demonstrated.     

Enantiospecific synthesis of the proposed structure of the antitubercular marine diterpenoid pseudopteroxazole: revision of stereochemistry.

An enantiospecific synthesis of structure 1, previously assigned to the antitubercular marine natural product pseudopteroxazole, has been accomplished as outlined in Scheme 1. Coupling of diene acid 3 and amino phenol 4 produced the amide 5, which was subjected to a novel oxidative intramolecular Diels-Alder reaction to generate the tricyclic lactam 6a stereoselectively. This product was transformed via intermediates 7-11 into the diene 13. Cationic cyclization of 13 afforded two diastereomeric tricyclic amphilectanes which were separated and transformed by parallel four-step sequences into 1 and 2, respectively. Neither 1 nor 2 were identical with pseudopteroxazole, indicating a need for revision of the structure, probably to 16.     

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.     

Reaction of 1,6‐Dioxo‐2,4‐Diene with Aziridine and Secondary Amine

The (2E,4E)‐ and (2E,4Z)‐1‐phenyl‐1,6‐dioxo‐hepta‐2,4‐diene reacts with aziridine to give aziridinecyclopentenol 3. This product arises from an intermolecular Michael addition of a nitrogen lone pair to the less reactive enone, followed by an intramolecular aldol reaction of the enol with ketone. Furthermore, the initially formed enol did not undergo nucleophilic attack onto the aziridine ring to form heterocycles. Interestingly, the reaction with secondary amine did not give the cyclopentenol adduct, and this only leads to the isomerization of (2E,4Z)‐1‐phenyl‐1,6‐dioxo‐hepta‐2,4‐diene to the more stable (2E,4E)‐1‐phenyl‐1,6‐dioxo‐hepta‐2,4‐diene by addition to the more reactive enone.     

呋喃环参与的Diels-Alder反应及其应用

呋喃环在作为Diels-Alder反应的二烯组份中得到了广泛的研究.本文就呋喃环参与的分子间和分子内D-A反应及其应用作一综述.     

Total synthesis of (+/-)-alantrypinone by hetero Diels-Alder reaction

An efficient total synthesis of (+/-)-alantrypinone 4 by hetero Diels-Alder reaction of a novel pyrazine diene 9 with either a functionalized 3-alkylideneoxindole or 3-methyleneoxindole itself is described. The Diels-Alder reactions provide both the desired regiochemistry and exo selectivity. An interesting anionic equilibration between alantrypinone 4 and its epimer 31 or between its ester analogues 23 and 24 has been demonstrated, and a mechanism has been proposed.     

Intramolecular Diels-Alder reaction in ionic liquids: effect of ion-specific solvent friction

The present work aims at understanding the role of viscosity or solvent friction in ionic liquids for an intramolecular Diels-Alder (IMDA) reaction of (E)-1-phenyl-4-[2-(3-methyl-2-butenyloxy)benzylidene]-5-pyrazolone (1). The results have been analyzed on the basis of the current theoretical models, and their failure to account for the observed trends is discussed in terms of "effective" viscosity or microviscosity. The rates of the reaction decrease with the increasing viscosity of the ionic liquids. As evident from the anionic effect, the solute-solvent specific interactions play a role in governing the kinetics of the reaction. The lower viscosities of the bistrifluoromethanesulfonimide [NTf2](-) based ionic liquids as compared to those based on tetrafluoroborate [BF4](-) anion fail to result in a corresponding acceleration in the rates of the reaction. These contradictory results indicate that solvent microviscosity, rather than the bulk macroscopic viscosity, should be the criteria for selecting the ionic liquids as reaction media.     

Reaction of (Z)-1-aryl-3-hexen-1,5-diynes with sodium azide: synthesis of 1-aryl-1H-benzotriazoles

[reaction: see text] A novel tandem cascade reaction involving 1,3-dipolar cycloaddition reaction, anionic cyclization, and sigmatropic rearrangement for the synthesis of 1-aryl-1H-benzotriazoles 2 and 3 was accomplished by treatment of the (Z)-1-aryl-3-henen-1,5-diynes (1) with sodium azide in DMF or DMSO at 80 degrees C for 12 h and gives 65-91% yields.     

Intramolecular Diels-Alder chemistry of 4-vinylimidazoles

An investigation of 4-vinylimidazoles as diene components in the intramolecular Diels-Alder reaction is described. In the course of these studies several parameters affecting the cycloaddition were evaluated including the nature of the imidazole protecting group, the type of dienophile and the linking group. These investigations established that amino linkers were generally more effective than either ethers or esters. In most cases, the cycloadditions were highly stereoselective, resulting in the formation of products derived from an anti transition state. The polysubstituted tetrahydrobenzimidazole core of the pyrrole-imidazole alkaloid ageliferin can be constructed through the use of pseudo dimeric 4-vinylimidazoles.     

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.     

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.     

First example of intramolecular [2π + 2π] alkene-arene photocyclization in the chromone series and its synthetic utility

Diels-Alder adducts of chromones are shown to undergo an intramolecular [2_π+2_π] alkene-arene photocyclization, leading to a versatile polycyclic diene, which is capable of dimerization or can be introduced into a high-yielding photoprotolytic oxametathetic sequence. This allows for an expeditious growth of molecular complexity over a few experimentally simple steps with stereochemistry being defined and locked at the very first Diels-Alder step. The overall reaction can potentially be utilized in diversity-oriented synthesis as it allows for three or more diversity inputs furnishing novel unique polycyclic scaffolds, which can readily be decorated with a variety of functionalities and aromatic/heterocyclic pendants.     

Synthesis of the tricyclic core of vinigrol via an intramolecular Diels-Alder reaction

[reaction: see text] Herein, we present a successful synthesis of the tricyclic core of vinigrol (1). Our approach takes advantage of a highly regioselective intramolecular Diels-Alder reaction of the diene 11 to construct two rings of the tricyclic vinigrol skeleton 12.     

Synthesis of 2,5-disubstituted octahydroquinolin-4-ones via anintramolecular hetero Diels-Alder reaction

A route for the preparation of 2,5-disubstituted octahydroquinolin-4-ones, synthetic precursors of the decahydroquinoline-type toxins, is presented. The key steps are an asymmetric epoxidation and an intramolecular hetero Diels-Alder reaction between an activated diene and an imine. The presence of an allylic stereogenic center induces some selectivity and thus only two cycloadducts are obtained in 70:30 ratio and good yield.     

A new diene, 2-methoxy-1,3-pentadiene-5-ol. Synthesis and intramolecular diels-alder reactions

Reactions of the diene 1-benzyloxy-2-methoxy-1,3-pentadiene-5-ol in intramolecular Diels-Alder reactions using maleic anhydride or fumaric acid ethyl ester is described. The new reactive diene is prepared starting from 3-methoxypyridine. The structure of the diene was elucidated by a NOE nmr experiment.     

A formal total synthesis of dysidiolide

[structure] A formal total synthesis of the natural product dysidiolide is described. Starting from a Diels-Alder reaction between an enoate and a Rawal diene, the cyclohexenone 4 was synthesized. A subsequent stereospecific methyl cuprate addition established the desired trans configuration in the cyclohexane 3. Wacker oxidation of the pentenyl side chain to the diketone 17 followed by an intramolecular aldol condensation led to the bicyclic enone 2, a key intermediate in a recently reported synthesis of dysidiolide.     

Total synthesis of natural dysidiolide

Dysidiolide (1), a novel sesterterpenoid previously isolated from the Caribbean sponge Dysidea etheria de Laubenfels, inhibits the action of the protein phosphatase, cdc25A. The authors establish a novel total synthesis of natural dysidiolide (1) using intramolecular Diels-Alder reaction as the key step from optically active cyclohexenone 3. Decalin, the core structure of 1, was constructed by intramolecular Diels-Alder reaction of the diene ester generated by elimination of the phenyl sulfoxide group from sulfoxide ester 6 prepared from cyclohexenone 3. Diastereoselective methylation at C-7, alkylation at C-6, and deoxygenation of C-12 and C-24 positions gave the fully substituted bicyclic core of 1. The two side chains of the bicyclic core were further extended so as to afford natural dysidiolide (1). The total yield of this synthesis exceeds that of previous syntheses of 1.     

An intramolecular Diels-Alder strategy for the asbestinins: enantioselective total syntheses of 11-acetoxy-4-deoxyasbestinin D and asbestinin-12

The enantioselective total syntheses of 11-acetoxy-4-deoxyasbestinin D and asbestinin-12 have been completed. A glycolate aldol reaction provided a diene useful for ring-closing metathesis to form an oxonene, which was ultimately employed as a template to execute a highly stereoselective intramolecular Diels-Alder cycloaddition, forming the hydroisobenzofuran moiety. The absolute configuration of the asbestinin subclass was confirmed via these synthetic efforts.     

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.     

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.