Cyclopentadiene Adducts Research Articles

Synthesis of Polycyclic Olefinic Monomers from Norbornadiene for Inverse Vulcanization: Structural and Mechanistic Consequences.

The preparation of high-sulfur content organosulfur polymers has generated considerable interest as an emerging area in polymer science that has been driven by advances in the inverse vulcanization polymerization of elemental sulfur with organic comonomers. While numerous new inverse vulcanized polysulfides have been made over the past decade, insights into the mechanism of inverse vulcanization and structural characterization of the high-sulfur-content copolymers remain limited in scope. Furthermore, the exploration of new molecular architectures for organic comonomer synthesis remains an important frontier to enhance the properties of these new polymeric materials. In the current report, the first detailed study on the synthesis and inverse vulcanization of polycyclic rigid comonomers derived from norbornadiene was conducted, affording a quantitative assessment of polymer microstructure for these organopolysulfides and insights into the inverse vulcanization polymerization mechanism for this class of monomers. In particular, a stereoselective synthesis of the endo-exo norbornadiene cyclopentadiene adduct (Stillene) was achieved, which enabled direct comparison with the known exo-exo norbornadiene dimer (NBD2) previously used for inverse vulcanization. Reductive degradation of these sulfur copolymers and detailed structural analysis of the recovered sulfurated organic fragments revealed that remarkable exo-stereospecificity was achieved in the inverse vulcanization of elemental sulfur with both these polycyclic dienyl comonomers, which correlated to the robust thermomechanical properties associated with organopolysulfides made from NBD2 previously. Melt processing and molding of these sulfur copolymers were conducted to fabricate free-standing plastic lenses for long-wave infrared thermal imaging.

Reaction of the levoglucosenone Diels–Alder adducts with acetaldehyde under the McMurry conditions

Reactions of acetaldehyde with Diels–Alder adducts of levoglucosenone with butadiene, isoprene, and cyclohexa-diene assisted by low-valence titanium afford products of acetaldehyde addition to the acetal center with opening of the 1,6-anhydro bridge. In the case of the cyclopentadiene adduct, the reaction gives the product of addition of the ethyl substituent to the acetal center while the 1,6-anhydro bridge remains unchanged.

Synthesis of the Polyoxygenated Cyclohexanoid Core of Bioactive Glycosides Xylosmin and Flacourtosides E and F.

A flexible synthesis of the carbocyclic core present in glycosides xylosmin and flacourtosides E and F, natural products exhibiting antimalarial and antiarboviral activities, has been accomplished. Our approach emanates from the Diels-Alder adduct of cyclopentadiene and MOM-protected 2-hydroxymethyl- p-benzoquinone and takes advantage of the stereochemical propensity of the norbornyl-fused scaffolds to generate the dense oxy-functionalization pattern with stereocontrol, enroute to a racemic synthesis of the carbocyclic core present in the aforementioned bioactive materials. This effort augurs well for exploring chemical diversity space around their scaffold.

Isomerization and functionalization of 2:1 Diels–Alder adducts of cyclopentadiene and p-benzoquinone: Applications to polycycles via ring-closing metathesis and ring-opening metathesis as key steps

Five stereochemically different 2:1 Diels–Alder adducts were prepared starting with cyclopentadiene and p-benzoquinone. Separately, these adducts were treated with an excess amount of base and allyl bromide to deliver two different tetra-allylated products. These allyl derivatives gave the corresponding mono-propellane derivatives on metathesis sequence. Five Diels–Alder adducts on treatment with Grubbs ruthenium catalysts delivered the corresponding mono- and di-ring-opened metathesis products. Structures of three functionalized adducts were determined by single-crystal X-ray diffraction studies.

Stability and Reactivity of 1,3-Benzothiaphosphole: Metalation and Diels–Alder Chemistry

The synthesis and functionalization of the parent 1,3-benzothiaphosphole is reported. The phosphole could not be isolated, but the compound could be manipulated in solution to produce several new phosphorus compounds. Metalation of the 2-position using lithium diisopropylamide proceeded smoothly according to 31P NMR spectroscopy, and quenching with trimethylsilyl chloride resulted in the desired 2-(trimethylsilyl)-1,3-benzothiaphosphole. The P═C bond of the thiaphosphole was also explored as a dienophile in Diels–Alder reactions with isoprene, 2,3-dimethylbutadiene, 2,3-dibenzylbutadiene, and cyclopentadiene. The fused-ring structures were fully characterized, and a solid-state molecular structure of the 2,3-dimethylbutadiene cycloadduct was obtained. Residual dipolar coupling (RDC) NMR experiments were used to assign major and minor products for the isoprene and cyclopentadiene adducts.

A total synthesis of the epoxyquinone natural product cytosporin D

A synthesis of epoxyquinone natural product cytosporin D from the readily available Diels–Alder adduct of cyclopentadiene and 2-prenyl-p-benzoquinone, has been accomplished. This approach leverages the stereochemical predisposition of the norbornyl-fused systems towards convex face reactivity as an enabler for the stereoselective construction of the pyran ring.

Concise Approach to the Carbocyclic Core of the Naturally Occurring Sphingomyelinase Inhibitor Scyphostatin

A flexible strategy toward the carbocyclic core of the naturally occurring sphingomyelinase inhibitor scyphostatin, from the readily available Diels-Alder adducts of cyclopentadiene and 2-allyl-p-benzoquinone, has been devised. This approach leverages the stereochemical predisposition of the norbornyl-fused scaffolds to generate the desired stereochemical pattern and leads to a concise synthesis of the epoxycyclohexenoid core of scyphostatin with a manipulable allyl side arm.

An Approach to seco-Prezizaane Sesquiterpenoids: Enantioselective Total Synthesis of (+)-1S-Minwanenone

A strategy of general applicability toward seco-prezizaane sesquiterpenes, from a chiral, tricyclic synthon, readily available via an enzymatic resolution step from the Diels-Alder adduct of cyclopentadiene and p-benzoquinone, has been devised. Our approach enables harnessing of the stereochemical proclivities of the norbornyl system to install the desired stereochemistry at the key stereogenic centers. Recourse to an interesting stratagem to realign a stereochemical divergence into stereoreconvergence forms the cornerstone of our successful approach. The first total synthesis of (+)-1S-minwanenone, a prototypical member of seco-prezizaane subclass, has been accomplished.

Total Synthsis of (+)-Ambuic Acid: α-Bromination with 1,2-Dibromotetrachloroethane

Total synthesis of (+)-ambuic acid has been accomplished from the readily available stereocontrolled Diels-Alder adduct of cyclopentadiene and iodo-1,4-benzoquinone monoketal through an efficient series of steps. A new method for the highly commendable synthesis of α-brominated Diels-Alder adduct is described.

Stereoselective Synthesis of Novel Diels–Alder Adducts of p-Substituted Methyl Thiocinnamates and Cyclopentadiene

This article describes the Diels–Alder reaction between methyl thiocinnamates, substituted at the para position by electron-donating and electron-withdrawing groups, with cyclopentadiene in the presence of catechol boron bromide (CBB) as a Lewis acid catalyst. The adduct configuration was confirmed by 1H NMR coupling constants and single-crystal x-ray diffraction. Total endo stereoselectivity was observed in all reactions and was attributed to the effective secondary interaction between the boron atom and the incipient double bond in the norbonene resulting from the planar geometry of the catalyst. 13C NMR chemical shifts of the coordinated dienophile carbonyl carbons with CBB compared to those of the non coordinated thiocinammates suggest a strong complexation with the catalyst.

Separation and Characterization of C70(C14H10) and C70(C5H6) from an Acetylene–Benzene–Oxygen Flame

Although derivatives of fullerenes are prevalent in the fullerene-producing flame, the chemistry of these derivatives has rarely been discussed in the previous literature. In this paper, two D5h-C70 derivatives, C70(C14H10) and C70(C5H6), were isolated from the soot of an acetylene–benzene combustion. On the basis of detailed MS, NMR, IR, and UV/vis analyses in combination with DFT calculations, the cycloadduct structures of C70(C14H10) and C70(C5H6) were identified. Both the anthracene (C14H10) and the cyclopentadiene (C5H6) adducts, supposed as the intermediate species produced during the combustion process, were characterized to bond at a [6,6] ring junction at the end of the olivary C70 cage. The present work exemplifies the capture of possible intermediates by the C70 fullerene from the flame and thus provides insight into the mechanism responsible for the formation of fullerene-containing soot.

Retro‐Diels–Alder Reactions of Masked Cyclopentadienones Catalyzed by Heterogeneous Brønsted Acids

AbstractThe zeolite H‐Beta catalyzes the retro‐Diels–Alder reaction of a range of cyclopentadiene cyclo‐adducts at moderate temperatures and ambient pressure, in the presence of an active dienophile. The active catalyst was identified and optimum reaction conditions established after screening a range of zeolites in the retro‐Diels–Alder reaction of the cyclopentadiene adduct of cyclopentenone. Our results suggest that retro‐Diels–Alder reactions of tricyclodecadienones are catalyzed by Brønsted acids and the high catalytic performance of H‐Beta catalysts can be ascribed to the optimal balance between the number of acid sites and their strength as well as to the accessibility of these sites. The methodology was then applied to a series of alkyl derivatives of cyclopentadienylcyclopentenones to provide a viable alternative synthetic route to 4‐alkylcyclopentenones and the versatility of the approach was demonstrated by the successful cycloreversion of N‐cyclohexyl‐2‐azanorborn‐5‐ene.

ChemInform Abstract: The 1:1 and 2:1 Adducts of Cyclopentadiene with p-Benzoquinone.

The exo-cis isomer (8) of the well-known endo-cis 1:1 adduct (4) of cyclopentadiene and p-benzoquinone has been obtained by heating the endo-cis-anti-cis-endo 2:1 adduct (13) with p-benzoquinone an...

ChemInform Abstract: Intramolecular Ene Reactions of Thioaldehydes Giving α-Mercapto Lactones.

The crystalline acids 3b, 4b and 5b and 6b, formally cycloadducts of anthracene, 9,10-dimethylanthracene and cyclopentadiene, respectively, with thioxoacetic acid (HO2CCHS), have been used to prepare esters with various allylic and homoallylic alcohols. These esters dissociated when heated, either in toluene under reflux or under the conditions of flash vacuum pyrolysis (FVP), to liberate transient thioaldehydes (thioxoacetate esters), which underwent intramolecular ‘ene’ reactions. Thus, the anthracene derivative 3c, in toluene at 111 °C gave, via prenyl thioxoacetate 2c, cis-2-mercapto-3-isopropenylbutyrolactone 13 in good yield. The corresponding cyclopentadiene derivatives 5c and 6c gave the same product, as a mixture of cis and trans isomers, essentially quantitatively when subjected to FVP. Similar experiments, involving Type [1, 1] intramolecular ene reactions, gave the α-mercapto-γ-lactones 20, 21 and 22, and the epimeric amercapto-δ-lactones 26. Further, the cyclopentadiene adduct 6h of 2-methylprop-2-enyl thioxoacetate 2h gave, under FVP conditions, the α-mercapto-δ-lactone 27 by a Type [2, 1] ene reaction. Evidence supporting a concerted mechanism for the ene reactions is discussed.Improved preparations of the cycloadducts 3b and 4b of thioxoacetic acid 2b with anthracene and dimethylanthracene, respectively, are recorded.

Enantioselective total synthesis of the novel antiproliferative metabolite (+)-hexacyclinol

An enantioselective total synthesis of the novel bioactive epoxyquinone natural product (+)-hexacyclinol, exhibiting promising growth inhibiting activity against cancer cell lines, has been accomplished from a readily available chiron derived from the Diels–Alder adduct of cyclopentadiene and p-benzoquinone.

Medicinal chemistry of polycyclic cage compounds in drug discovery research

Saturated polycyclic hydrocarbon structures such as the monocyclic octane, bicylic norbornane and tricyclic adamantane have attracted the attention of several research groups since the 1930s. In the 1950s the synthesis of the so called bird-cage pentacyclo[5.4.0.02,6.03,10.05,9]undecane-8,11-dione, also known as Cookson’s diketone was reported. This pentacyclic cage diketone is the product of the intramolecular photocyclized Diels Alder adduct of p-bensoquinone and cyclopentadiene. The conversion of this diketone to its monoketone analog formed the basis of a variety of monosubstituted derivatives. Furthermore, acid-based rearrangement reactions of hydroxyl-substituted compounds led to, amongst others, the unique D3-trishomocubane symmetrical compounds, which consists of only five-membered carbon rings. The D3 stereoisomerism of the trishomobubane affords unique chemical challenges with potential medicinal implications. The medicinal chemistry of these cage compounds gained momentum in the 1980s with the discovery of the calcium-channel-modulating effects and antiviral activity thereof. The 1990s and 2000s saw several reports on a variety of pharmacological areas, i.e., dopaminergic, catecholaminergic, and focusing on disorders, in particular that of the central nervous system, such as neurodegeneration (Parkinson’s disease). These polycyclic structures have proved to be very useful in drug discovery research, in particular during the past 25 years.

Preparation and structure of pyrrolo[2,1- b]- and isoindolo[1,2- b][3,1]epoxyquinazolines

Various γ-oxocarboxylic acids [aroylpropionic acids, cis-2-(4-methylbenzoyl)cyclohexanecarboxylic acid, diendo-3-benzoylbicyclo[2.2.1] heptane-2-carboxylic acid, formylbenzoic acid, methanobenzenecyclooctencarboxylic acid and the cyclopentadiene adduct of 3- trans-(4-methylbenzoyl)acrylic acid] were reacted with diexo-3-aminomethyl-7-oxabicyclo[2.2.1]hept-5-en-2-ylamine 2 to result in condensed pyrroloepoxyquinazolines 3– 10. The starting 2 retained the diexo configuration, but cis → trans isomerization took place when cis-2-(4-methylbenzoyl)cyclohexanecarboxylic acid was applied. The structures, including the ring annelations and the position of the aryl group on the new chiral centre, were established by means of NMR spectroscopy, and in the cases of the trans-3-(4-methylbenzoyl)acrylic acid–cyclopentadiene adduct for 10a, 10b and 10c by X-ray crystallography.

Enantioselective total synthesis of the polyketide natural product (−)-EI-1941-2: a novel interleukin-1β converting enzyme (ICE) inhibitor

An enantioselective total synthesis of the novel bioactive epoxyquinone natural product (−)-EI-1941-2, exhibiting promising ICE inhibiting activity, has been accomplished from a readily available chiron derived from the Diels–Alder adduct of cyclopentadiene and p-benzoquinone.

Toward Isolated Molecular Wires: A pH-Responsive Canopied Polypyrrole

The design, synthesis, and electropolymerization of sterically hindered pyrrole derivatives are described. Endo and exo adducts of cyclopentadiene and N-phenylmaleimide were converted to give bicyclo[2.2.1]heptane-fused pyrrole monomers, in which a phenyl group is rigidly placed proximate the pyrrole fragment. Oxidative polymerization of these monomers affords highly conductive polypyrroles. The rigid molecular scafffold of the pyrrole monomers limits cross-communication between adjacent conducting strands and produces a defined narrow potential window of high conductivity dominated by intrachain polaronic charge carriers. The resultant loosely packed polymer chains allow for superior sensory properties. Notably, the electrical conductivity of oxidatively doped poly(7) could be reversibly modulated in aqueous electrolytes at pH 3−9.

A Total Synthesis of the Epoxyquinone Based Antifungal Natural Product (.+‐.)‐Ambuic Acid.

Abstract A total synthesis of the recently isolated polyketide natural product (±)-ambuic acid has been accomplished from the readily available Diels–Alder adduct of cyclopentadiene and 2-allyl-p-benzoquinone through a simple sequence with sound stereocontrol.