Intramolecular Diels-Alder Reaction Of Furans Research Articles

Total Synthesis of (±)-Prostratin

Summary Prostratin, a highly complex diterpene natural product, is a pre-clinical candidate in developing a cure for HIV-1 infection and also a potent and selective inhibitor of several tumors. Despite nearly 40 years of progress, prostratin and related natural products still present formidable challenges for synthetic chemists. Here, we report a total synthesis of (±)-prostratin that proceeds in 23 steps from cyclopentadiene. The synthetic strategy includes rapid assembly of the tricyclic core and highly controlled establishment of the densely functionalized C ring, featuring an array of stereoselective transformations including alkoxide-guided 1,4-additions and cyclopropane formation. This work should enable further explorations of chemical and biological spaces based on prostratin and related natural products.

Synthesis of Electron‐Deficient Tetrahydro‐ and Dihydroimidazo[1,2‐f]phenanthridines by Microwave‐Mediated IMDAF Reactions

N‐Substituted tetrahydroimidazo[1,2‐f]phenanthridines (TIPs) and dihydroimidazo[1,2‐f]phenanthridines (DIPs) have a variety of interesting properties, but structural variations of these compounds have, until now, included nitrogen substituents. Herein, TIPs and DIPs that have electron‐withdrawing groups on the phenanthridine moiety have been synthesized. A microwave‐mediated one‐pot intramolecular Diels–Alder reaction of furan (IMDAF) and subsequent aromatization were employed as the key steps. The electron‐deficient dihydrophenanthridines constructed by an IMDAF were oxidized in situ by 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ), and the salts generated were treated with benzylamine to give N‐benzyl TIP compounds. These TIPs were remarkably stable towards air‐mediated oxidation relative to those TIPs that do not contain electron‐withdrawing substituents and were isolated in high yields. Electron‐deficient TIPs were easily oxidized to give the corresponding DIPs by treatment with N‐bromosuccinimide.

Gold-Catalyzed Cyclization of Furan-Ynes bearing a Propargyl Carbonate Group: Intramolecular Diels-Alder Reaction with In Situ Generated Allenes.

Gold-catalyzed cyclization of various furan-ynes with a propargyl carbonate or ester moiety results in the formation of a series of polycyclic aromatic ring systems. The reactions can be rationalized through a tandem gold-catalyzed 3,3-rearrangement of the propargyl carboxylate moiety in furan-yne substrates to form an allenic intermediate, which is followed by an intramolecular Diels-Alder reaction of furan and subsequent ring-opening of the oxa-bridged cycloadduct. It was found that the steric and electronic properties of phosphine ligands on the gold catalyst had a significant impact on the reaction outcome. In the case of 1,5-furan-yne, the cleavage of the oxa-bridge in the cycloadduct with concomitant 1,2-migration of the R(1) group occurs to furnish anthracen-1(2H)-ones bearing a quaternary carbon center. For 1,4-furan-yne, a facile aromatization of the cycloadduct takes place to give 9-oxygenated anthracene derivatives.

ChemInform Abstract: A Simple Preparative Synthesis of Epoxy[1,3]oxazino(or oxazolo)[2,3‐a]isoindoles and Their Thia Analogues via IMDAF.

AbstractThe intramolecular furan Diels—Alder reaction (IMDAF) of azomethines, prepared from furfurals and amino alcohols or thiols, with dienophiles (III) and (IX) affords the title skeletons in low to moderate yields.

The first example of an intramolecular Diels–Alder furan (IMDAF) reaction of iminium salts and its application in a short and simple synthesis of the isoindolo[1,2- a]isoquinoline core of the jamtine and hirsutine alkaloids

1-(2-Furyl)-3,4-dihydroisoquinolines, easily prepared from readily available phenethylamines, undergo tandem alkylation/[4+2]-cycloaddition with allyl halides. The reaction proceeds via 2-allyl-1-furyl-3,4-dihydroisoquinolinium salt formation and subsequent intramolecular exo-Diels–Alder reaction of furan with the allyl fragment (IMDAF reaction). The adducts formed include the basic structural element of the isoindolo[1,2- a]isoquinoline alkaloids jamtine and hirsutine.

Synthetic and Theoretical Investigations on the Construction of Oxanorbornenes by a Michael Addition and Intramolecular Diels–Alder Furan Reaction

AbstractThe conjugate addition of nucleophiles such as allylmercaptan, allyl‐ and homoallylmalonate and diallylamine to β‐furyl enones and acrylate, provides the Michael adducts in good yield. A facile intramolecular Diels–Alder reaction between the unsaturated tether and the furan diene ensues when these adducts are heated in a solvent such as toluene orxylene to afford the cycloadducts in good yield and excellent stereoselectivity in most cases. The structure and stereochemistry of these cycloadducts were confirmed by extensive NMR experiments and X‐ray crystallography. Quantum chemical calculations on the transition state and product geometries suggest that the formation of the cycloadducts, in which the newly formed ring is exo‐fused to the oxanorbornene framework, is favored over the endo‐fused product due to less strain in the former and its transition state.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Synthesis of Advanced Intermediates of Lennoxamine Analogues

Correction to: Synthesis of Advanced Intermediates of Lennoxamine AnaloguesSynthesis 2007; 2007(07): 1091-1095DOI: 10.1055/s-2007-965950

An efficient approach to isoindolo[2,1- b][2]benzazepines via intramolecular [4+2] cycloaddition of maleic anhydride to 4-α-furyl-4- N-benzylaminobut-1-enes

Acylation of 4-α-furyl-4- N-benzylaminobut-1-enes with maleic anhydride gave 4-oxo-3-aza-10-oxatricyclo[5.2.1.0 1,5]dec-8-ene-6-carboxylic acid via amide formation followed by intramolecular Diels–Alder reaction of furan (IMDAF). The cycloaddition proceeded under mild reaction conditions (25 °C) and provided only the exo-adduct in quantitative yield. Treatment of this compound with PPA gave isoindolo[2,1- b][2]benzazepine derivatives via ring opening, aromatization and intramolecular electrophilic alkylation. In order to extend the scope of the reaction sequence, 7-oxo-5,11b,12,13-tetrahydro-7 H-isoindolo[2,1- b][2]benzazepine-8-carboxylic acids were further transformed into useful synthetic intermediates.

ChemInform Abstract: Synthetic Approaches Towards Phorbols via the Ultra‐High‐Pressure Mediated Intramolecular Diels—Alder Reaction of Furans (IMDAF): Effect of Furan Substitution.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Preparation of tricyclic nitrogen heterocycles via intramolecular Diels-Alder reaction of furans

Preparation of rigid tricyclic nitrogen heterocycles through acylation of N-alkylfurfurylamines with fumaric and maleic acid derivatives has been studied. The reaction proceeds via an initial amide formation followed by an intramolecular Diels-Alder (IMDA) reaction. Various acylation conditions have been studied. Influence of steric and electronic effects on the product formation has also been investigated.

Synthetic approaches towards phorbols via the ultra-high-pressure mediated intramolecular Diels–Alder reaction of furans (IMDAF): effect of furan substitution

Tricyclic structures having the functionality and stereochemistry inherent in phorbol and its analogues may be rapidly constructed by an ultra-high pressure IMDAF reaction. The nature of the 2-thioether substituent on the furan diene is critical for the success of the key cycloaddition reaction.

Intramolecular Diels-Alder reaction of furans with allenyl ethers followed by trimethylsilyl group 1,2-rearrangement and Brook rearrangement

The base-catalyzed intramolecular Diels-Alder reactions of 5-trimethylsilyl-2-furfuryl propargyl ethers 1a-1f gave compounds 2a-2f and 3a-3f in 70–90% yields respectively, a novel reaction involving an intramolecular Diels-Alder reaction followed by a trimethylsilyl group 1,2-rearrangement and Brook rearrangement.

Intramolecular Diels-Alder reactions of furans with a merely strain-activated tetrasubstituted alkene: Bicyclopropylidene

Bicyclopropylidene derivatives 1, 6, 8 with furan moieties attached on tethers of various length and nature all undergo clean intramolecular Diels-Alder reactions with complete endo-diastereoselectivities when heated to 70 – 130°C, under 10 kbar pressure. The reaction rates are at least as high or higher than those of analogously tethered methylenecyclopropane-furan derivatives 15, 17, 20, in spite of the fact that the reactive double bond in bicyclopropylidene is tetrasubstituted and not activated by any electron withdrawing group.

Study on the reaction mechanism of the base-catalyzed intramolecular Diels-Alder reaction of furfuryl propargyl ethers

There is considerable current interest in the intramolecular Diels-Alder reaction, and it has been applied to a number of synthetic objectives with notable success.1 The vast majority of the work reported in this area has dealt with reactions utilizing ethylenic and acetylenic dienophiles. On the other hand, the intramolecular DielsAlder reaction of allene has received much less attention.2 A decade ago, Kanematsu et al. demonstrated that the allene unit is a versatile synthon as a dienophile in the intramolecular cycloaddition due to the absence of unfavorable nonbonded interactions in the transition state.3 Afterward, they developed a furan ring transfer reaction via the intramolecular Diels-Alder reaction of furan diene and allenyl ether dienophile and applied this reaction to the synthesis of natural product^,^ Scheme 1. For the purpose of furan ring transfer reaction, in all of their cases there were only one carbon atom and one oxygen atom connection between the furan diene and the allene dienophile for the cycloaddition. In these cases, the cycloadducts were not isolated under the reaction conditions but were further transferred to the isobenzofuran precursors via ring opening of the bridged oxygen ring of the cycloadducts. Recently, we accomplished the intramolecular Diels-Alder reactions of furans with allenyl ethers by varying the chain length and found the

High Pressure Mediated Intramolecular Diels-Alder Reactions of Furans with Unactivated Methylenecyclopropane Terminators

Furfuryl derivatives 3 with an allyl ether or allylamine type linkage to a methylenecyclopropane moiety readily undergo intramolecular Diels-Alder reactions at 10-12 kbar to yield interesting new spirocyclopropane-annelated tricyclic structures 4 diastereoselectively in excellent yields. The starting materials 3 are readily obtained by Pd0-catalysed nucleophilic allylic substitution on 1-chloro-1-ethenylcyclopropane 1 with furfurol or furfurylamine. Some acid-catalysed ring-openings of the 7’-methoxy derivative 4d are described as well. Furthermore, activation parameters for the intramolecular cycloaddition of 3a have been determined by means of on-line infrared spectroscopy under high pressure.

Intramolecular Diels-Alder Reaction of Furans with Allenyl Ethers: High Effect of the Chain Length on the Structure and Reactivity of the Cycloadducts

The structure and reactivity of the cycloadducts of the title reaction were found to be highly dependent on the chain length between the furan diene and the allenyl ether dienophile. Reaction of the propargyl ether (2) with t-BuOK in t-BuOH at 85°C for 3 h gave a mixture of the cycloadducts (3) and (4) in 90% yield, which were transferred to the benzo derivatives (5), (6) and (7). Treatment of the propargyl ether (8) with t-BuOK in t-BuOH at 85°C for 5 h gave the products (9) and (10) in a ratio of 8:1 in 65% yield, no detectable amount of the cycloadduct (8b) was obtained. Refluxing of the propargyl ether (13) with t-BuOK in t-BuOH at 85°C for 4 h gave the allenyl ether (14). Heating 14 in DMSO at 150°C for 12 h still did not give 15

Intramolecular Diels-Alder reaction of furans with allenyl ethers followed by methylthio group 1,4-rearrangement

The base-catalyzed intramolecular Diels-Alder reactions of the furfuryl propargyl ethers 1a–1e gave compounds 6a–6e as the major product respectively, a novel reaction involving an intramolecular Diels-Alder reaction followed by a methylthio group 1,4-rearrangement.

ChemInform Abstract: Synthetic Approaches to Phorbols via the Intramolecular Diels‐Alder Reactions of Furans (IMDAF): Oxygen Bridge Cleavage and High Stereocontrol During α′‐Benzylthio‐Substituted Furan Substrates.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthetic approaches to phorbols via the intramolecular Diels–Alder reactions of furans (IMDAF): oxygen bridge cleavage and high stereocontrol during cycloaddition using α′-benzylthio substituted furan substrates

High pressure mediated IMDAF of the α′-benzylthiofuran substrate 1 results in efficient and highly stereoselective cycloaddition; subsequent epimerisation of the cycloadduct 6 is regiospecific and the oxygen bridge may be opened by elimination or hydrolysis.

Synthetic approaches to phorbols via the intramolecular Diels–Alder reaction of furans: influence of the dienophile upon the stereochemical control

A carbotricycle (13) having the same relative stereochemistry as the phorbols at 6 centres has been constructed via stereoselective Intramolecular Diels–Alder reaction of furans (IMDAF) of a precursor (7) possessing a Z-vinylogous ketoester followed by selective epimerisation at C-10 of the initial cycloadduct (11); whereas the corresponding E-isomer (8) or alkyne (3) show no stereoselection in the IMDAF.