Intramolecular Diels-Alder Reaction Research Articles

ChemInform Abstract: Synthesis of Tribenzotropone by Ring Expansion of Phenanthrene‐9,10‐dione.

Tribenzotropone was efficiently synthesized by a ring-expansion method from readily available phenanthrene-9,10-dione via a ring-opened diketone as a key intermediate; the diketone was prepared by nucleophilic addition of allyl and vinyl groups, followed by an oxidative ring-opening reaction with lead(IV) acetate. Ring closure by an intramolecular Diels–Alder reaction and subsequent dehydrogenation produced tribenzotropone in 38% overall yield. Ring closure by a Morita–Baylis–Hillman reaction, on the other hand, produced a dibenzo-fused nonanedione in 22% overall yield.

Synthesis of the AB ring system of clifednamide utilizing Claisen rearrangement and Diels–Alder reaction as key steps

In order to construct the functionalized AB ring system of clifednamide, member of the class of macrocyclic tetramic acid lactams, a synthesis was developed which utilized an Ireland-Claisen rearrangement and an intramolecular Diels-Alder reaction. Starting from di-O-isopropylidene-d-mannitol the allyl carboxylate precursor for the sigmatropic rearrangement was prepared. This rearrangement proceeded diastereoselectively only in the presence of an allyl silyl ether instead of the parent enone in the side chain, as suggested by deuteration experiments. A subsequent Diels-Alder reaction yielded the target ethyl hexahydro-1H-indene-carboxylate with high diastereoselectivity. Quantum-chemical investigations of this intramolecular Diels-Alder reaction support the proposed configuration of the final product.

Thermal and Lewis acid promoted intramolecular Diels–Alder reaction of furanose tethered 1,3,9-decatriene systems: a synthetic and computational investigation

The intramolecular Diels–Alder (IMDA) reaction of furanose tethered 1,3,9-decatrienes (4a–4r) was investigated under thermal conditions and in the presence of a Lewis acid.

Inter- and Intramolecular Diels-Alder Reaction of Ethenetricarboxylate Derivatives

Inter- and Intramolecular Diels-Alder Reaction of Ethenetricarboxylate Derivatives

Total Synthesis of (-)-Hymenosetin.

The 3-decalinoyltetramic acid (-)-hymenosetin and its N-methyl analogue were prepared in 11 and 8 steps, respectively, from (+)-citronellal using an intramolecular Diels-Alder reaction as the key step. This method represents the first example for the synthesis of a 3-decalinoyltetramic acid with a free NH moiety. The stereochemistry of the title compound, an unnatural diastereomer, and of a decalin building block was studied in detail using circular dichroism spectroscopy in the IR and UV/VIS freqeuncy range. This allowed to determine the absolute configuration of the natural product and to plan the synthetic route.

Mechanism for covalent dimerization of pyridine: [4+2] dimerization, an MP2 investigation

The Diels⿿Alder (DA) covalent dimerization mechanisms of pyridine were studied at the MP2/6-311G(d,p) level. Involvement of N atom in DA reaction causes high barrier height, otherwise the barrier heights are low. The two most stable DI dimers formed by intermolecular DA reaction (b-γDI and b-γ⿲DI) and the two most stable DII dimers formed by further intramolecular DA reaction (c-γDII and c-γ⿲DII) were located with relative energy of 26.6 and 26.1kcal/mol, and 32.1 and 31.6kcal/mol, respectively, higher than two moles of pyridines. Theoretical results suggested that DA dimerization of pyridine is slightly easier than that of benzene.

Niizalactams A-C, Multicyclic Macrolactams Isolated from Combined Culture of Streptomyces with Mycolic Acid-Containing Bacterium.

A terrestrial bacterium, Streptomyces sp. NZ-6, produced niizalactams A-C (1-3), unprecedented di- and tricyclic macrolactams, by coculturing with the mycolic acid-containing bacterium Tsukamurella pulmonis TP-B0596. Their complete structures, including absolute configurations, were elucidated on the basis of spectroscopic data and chemical derivatization. Their unique skeletons are proposed to be biosynthesized from a common 26-membered macrolactam intermediate by SN2 cyclization or an intramolecular Diels-Alder reaction.

Medium-Ring Effects on the Endo/Exo Selectivity of the Organocatalytic Intramolecular Diels-Alder Reaction.

The intramolecular Diels-Alder reaction has been used as a powerful method to access the tricyclic core of the eunicellin natural products from a number of 9-membered-ring precursors. The endo/exo selectivity of this reaction can be controlled through a remarkable organocatalytic approach, employing MacMillan's imidazolidinone catalysts, although the mechanistic origin of this selectivity remains unclear. We present a combined experimental and density functional theory investigation, providing insight into the effects of medium-ring constraints on the organocatalyzed intramolecular Diels-Alder reaction to form the isobenzofuran core of the eunicellins.

Metal-Free Allene-Based Synthesis of Enantiopure Fused Polycyclic Sultones.

The controlled metal-free preparation of fused δ-sultone derivatives has been developed starting from hydroxyallenynes. The use of 2-(3,3-diethyltriaz-1-enyl)-4-methylbenzene-1-sulfonyl chloride in a sulfonylation/rearrangement sequence gives access to 1,3-dien-2-yl arenesulfonates. These functionalized enynes suffered a direct cyclization/desaturation radical cascade, allowing the synthesis of a variety of enynyl [1,2]oxathiine 1,1-dioxides. Stereoselective cyclization of the readily formed core through intramolecular Diels-Alder reaction has also been demonstrated, affording β-lactam- and glucofuranoside-fused δ-sultone polycycles. These selective reactions have been studied experimentally and additionally, their reaction mechanisms have been investigated computationally by means of density functional theory calculations.

A Second-Generation Chemoenzymatic Total Synthesis of Platencin

A total synthesis of the potent antibacterial agent platencin is described. The reaction sequence used involves, as starting material, an enantiomerically pure cis-1,2-dihydrocatechol derived from the whole-cell biotransformation of iodobenzene. Simple chemical manipulations of this metabolite provide a triene that engages in a thermally promoted intramolecular Diels–Alder reaction to establish the octa­hydro-2H-2,4a-ethanonaphthalene core of platencin.

ChemInform Abstract: Tandem Cross Enyne Metathesis (CEYM)—Intramolecular Diels—Alder Reaction (IMDAR). An Easy Entry to Linear Bicyclic Scaffolds.

AbstractStarting from non‐substituted olefin moieties, the linear bicyclic derivatives are obtained as a single diastereomer.

ChemInform Abstract: Stereoselective Total Syntheses of Guanacastepenes N and O.

Total syntheses of (±)-guanacastepenes N and O were accomplished with 2-cycloheptenone as starting material. The six- and five-membered rings of the core [5, 7, 6] ring skeleton were constructed with an intramolecular Diels–Alder reaction and α-carbonyl radical cyclization. The quaternary centers and their stereochemistry were established with sequential Cu(I)-mediated conjugate additions. A sequence with dihydroxylation, conjugate addition, and β-elimination was devised to incorporate all oxygen functionalities at positions. The total synthesis is adaptable for the synthesis of enantiopure guanacastepenes N and O using chiral intermediate (R)-3-vinyl-2-cycloheptenol obtained from lipase-catalyzed kinetic resolution.

Distortion, Tether, and Entropy Effects on Transannular Diels–Alder Cycloaddition Reactions of 10–18-Membered Rings

Density functional theory calculations were performed on a set of 13 transannular Diels-Alder (TADA) reactions with 10-18-membered rings. The results were compared with those for bimolecular and intramolecular Diels-Alder reactions in order to investigate the controlling factors of the high TADA reactivities. The effects of tether length, heteroatoms, and alkynyl dienophiles on reactivity were analyzed. We found a correlation between tether length and reactivity, specifically with 12-membered macrocycles undergoing cycloaddition most readily. Furthermore, modifying 12-membered macrocycles by heteroatom substitution and utilizing alkynyl dienophiles enhances the reaction rates up to 10(5)-fold.

ChemInform Abstract: N—B Dative Bond‐Induced [3.3.0] Bicyclic Boronate‐Tethered Exo‐Selective Intramolecular Diels—Alder Reaction.

AbstractAn operationally simple transformation of aryl and alkyl substituted alkenylboronic acids with aminodiacetic acid or aminodiethanol containing dienes is developed.

Solvent effect in diastereoselective intramolecular Diels–Alder reactions

In the process of improving the synthesis of a novel class of chiral drug scaffolds, first reported in 2010, we observed that the stereochemical outcome of the key chemical transformation appeared to be correlated to the solvophobicity of the reaction medium. Our mechanistic investigations by NMR monitoring of the reaction confirmed the proposed acylation/intermolecular cycloaddition sequence. The computational studies using DFT methods next predicted exo/endo stereoselectivity (4.3:1 in CHCl3, 1.6:1 in H2O) in agreement with the experimental results (3.3:1 in CHCl3, 1:1 in H2O). The observed stereoselectivity was related to the different level of asynchronicity of the diastereomeric transition states. This leads to different solvent stabilization of the cycloaddition transition state of one diastereomer more than the other.

ChemInform Abstract: The Intramolecular Diels—Alder Vinylfuran (IMDAV) Reaction: A Short Approach To Aza‐Analogues of Pinguisane‐Type Sesquiterpenes.

AbstractA domino sequence involving acylation of amines (I) with maleic anhydride, intramolecular Diels—Alder reaction, and proton shift steps provides the title compounds as single diastereoisomers.

ChemInform Abstract: On the Stereoselectivities of Some Hindered Diels—Alder Reactions.

AbstractBoth inter‐ and intramolecular Diels—Alder reactions of dienyl methyl fumarate [e.g. (I) and (III)] give cis‐fused lactones with a methyl bearing quaternary centre as the major products because of the influence of the methyl substituent.

Tandem cross enyne metathesis (CEYM)-intramolecular Diels-Alder reaction (IMDAR). An easy entry to linear bicyclic scaffolds.

A new tandem cross enyne metathesis (CEYM)–intramolecular Diels–Alder reaction (IMDAR) has been carried out. It involves conjugated ketones, esters or amides bearing a remote olefin and aromatic alkynes as the starting materials. The overall process enables the preparation of a small family of linear bicyclic scaffolds in a very simple manner with moderate to good levels of diastereoselectivity. This methodology constitutes one of the few examples that employ olefins differently than ethylene in tandem CEYM–IMDAR protocols.

Synthesis of Tribenzotropone by Ring Expansion of Phenanthrene-9,10-dione

Tribenzotropone was efficiently synthesized by a ring-expansion method from readily available phenanthrene-9,10-dione via a ring-opened diketone as a key intermediate; the diketone was prepared by nucleophilic addition of allyl and vinyl groups, followed by an oxidative ring-opening reaction with lead(IV) acetate. Ring closure by an intramolecular Diels–Alder reaction and subsequent dehydrogenation produced tribenzotropone in 38% overall yield. Ring closure by a Morita–Baylis–Hillman reaction, on the other hand, produced a dibenzo-fused nonanedione in 22% overall yield.

ChemInform Abstract: Recent Applications of Intramolecular Diels—Alder Reaction in Total Synthesis of Natural Products

AbstractReview: 141 refs.