Phytochemicals from Echinacea and Hypericum: A Direct Synthesis of Isoligularone

Reaction of trienes with α,β‐unsaturated aldehydes produces bicyclic products via a tandem Diels–Alder/ene reaction. The adduct from tiglic aldehyde was converted into isoligularone by conversion to a furan followed by benzylic oxidation.     

Synthesis of an Advanced Precursor of Demethoxyviridin

The synthesis of a potential precursor 3 to demethoxyviridin (1b) is described. The centerpiece of this strategy was the conversion of the previously described dibromoolefin 6 to the masked alkyne β-hydroxyaldehyde 5 in a single step. Further elaboration then produced the alkyne oxazole 4, which on thermolysis, followed by in situ tautomerization and silylation, led directly to 3.

Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for full experimental and spectral details.     

Dianions of Unsaturated Carboxylic Acids in Synthesis. Synthesis of Juvocimene I

Juvocimene I is prepared by a non ambiguous synthesis based on the regioselective alkylation of 4-methylhexa-2,4-dienoic acid, and Wittig olefination of the aldehyde corresponding to the alkylated acid.     

Facile Synthesis of Spiro Oxindoles,Azaoxindoles, and Dihydroisoquinolone

Formation of 1-aryl-4-oxo-cyclohexa(e)nonecarboxylates from the Diels–Alder cycloaddition of 2-trimethylsilyloxy-1,3-butadiene and Danishefsky diene with aryl- and pyridylacrylates and further conversion thereof to spirocycles is described. This provides an efficient method for spiro oxindoles, azaoxindoles, and dihydroisoquinolones.

Efficient Synthesis of Hexahydrocarbazoles

Selective reduction of the nitro group in methyl 1-(2-nitrophenyl)-4-oxo-cyclohex-2-enecarboxylates with zinc-acetic acid forms hexahydrocarbazoles. The reaction is applicable to the corresponding pyridyl analogs to generate azahexahydrocarbazoles. This provides an efficient method for the generation of tricyclic framework.

Synthesis and Characterization of Benzenesulfonyl Hydrazones and Benzenesulfonamides

In the search for structural cyclic imide analogues of therapeutic interest, the syntheses and characterization of benzenesulfonyl hydrazones and benzenesulfonamides are described. The benzenesulfonyl chlorides (2) and (3) were obtained through the Diels–Alder reaction between N‐p‐chloro‐sulfonylfenylmaleimide (1) and furan or 2‐methylfuran. The reactions of (2) and (3) with hydrazine and amines afforded the hydrazides and sulfonamides, respectively. The sulfonylhydrazones were obtained through a condensation between the sulfonylhydrazides with different benzaldehydes.     

Arrangement of C60 via the Self‐Assembly of Post‐Functionalizable Polyisocyanate Block Copolymer

Poly(furfuryl isocyanate) (PFIC), which includes the reactive furan group, was synthesized by anionic polymerization using a sodium benzhydroxide (Na‐BH), self‐assembly initiator. We determined the optimum polymerization conditions by varying both the reaction time and the molar ratio of the monomer to the initiator. Block copolymer, poly(furfuryl isocyanate)‐b‐poly(n‐hexyl isocyanate), was synthesized under optimized polymerization conditions. The PFIC was modified by Diels–Alder reactions with C60 for functionalization. Transmission electron microscopy (TEM) was used to study the self‐assembly of block copolymers and modified block copolymer with C60. C60 formed highly ordered aggregates on the PFIC domains via self‐assembly of the block copolymer.     

A Novel and Convenient Synthesis of Coenzyme Q1

Abstract

A convenient and efficient synthetic route to Coenzyme Q₁ (6) starting from 3,4,5‐trimethoxytoluene (1) is described. The key features of this synthesis include the Diels–Alder reaction of 2,3‐dimethoxy‐l,4‐benzoquinone (3) with cyclopentadiene and the introduction of a C₅ side chain to 4,5‐dimethoxy‐2‐methyltricyclo[6.2.1.0^2,7]undeca‐4,9‐diene‐3,6‐dione (4) under mild conditions, (6) was obtained in overall 60% yield.     

Synthesis and structure of a chiral areno-bridged [2.4]metacyclophane

The reductive coupling reaction of 1,4-bis(3-acetyl-5-tert-butyl-2-methoxyphenyl)butane 3 was carried out using TiCl₄-Zn in pyridine followed by a McMurry coupling reaction to afford the compounds anti and syn 1,2-dimethyl[2.4]MCP-1-ene 4. Bromination of 4 with BTMA-Br₃ in dry CH₂Cl₂ afforded the interesting compound 1,2-bis-(bromomethyl)-5,15-di-tert-butyl-8,18-dimethoxy[2.4]MCP-1-ene 6 and consecutive debromination with Zn and AcOH in CH₂Cl₂ solution afforded the stable solid 5,15-di-tert-butyl-8,18-dimethoxy-1,2-dimethylene[2.4]MCP 7 in 89% yield. Compound 7 was conveniently employed in a Diels–Alder reaction with dimethyl acetylenedicarboxylate (DMAD) to provide 2-(3′,6′-dihydrobenzo)-5,15-di-tert-butyl-8,18-dimethoxy[2.4]MCP-4′,5′-dimethylcarboxylate 8 in good yield. Diels–Alder adduct 8 was converted into a novel and inherently chiral areno-bridged compound [2.4]MCP 9 by aromatization. The chirality of the two conformers was characterized by circular dichroism (CD) spectra of the separated enantiomer which are perfect mirror images of each other.     

Synthesis of Trichlorophenol Derivatives

An expedient three‐step procedure for the synthesis of trichlorophenol derivatives based on the acid‐catalyzed rearrangement of the bicyclic ketone precursors 6a–e in high overall yield is described. The bicyclic ketone precursors 6a–e were obtained from Diels–Alder cycloadducts of β‐substituted vinyl acetates with tetrachloro‐5,5‐dimethoxycyclopentadiene in two steps.     

Oxidative Dearomatization: Synthesis of Functionalized Bicyclo[2.2.2]octenones,Sigmatropic Shift in Excited State,and Radical-Induced Cleavage of Cyclopropane Ring

Synthesis of novel bicyclo[2.2.2]octenones endowed with a β,γ-enone system in which γ-carbon is substituted with an electron-withdrawing group from simple aromatics is described. Oxa-di-pi-methane reaction of bicyclo[2.2.2]octenones to functionalized bicyclo[3.3.0]octanes and their transformation to bicyclo[3.2.1]octane framework are also presented.     

Cycloaddition of Cyclohexa-2,4-dienones with Nitroolefins: An Unusual Regioselectivity and Expeditious Entry into Nitro-bicyclo[2.2.2]octenones

Cycloaddition of electron-deficient cyclohexa-2,4-dienones with nitroolefins leading to functionalized bicyclo[2.2.2]octenones with nitro groups is reported. A highly unusual regioselectivity was observed. Crystal structure of one of adducts has also been reported.     

Allylsilane Reagent-Controlled Divergent Asymmetric Catalytic Reactions of 2-Naphthoquinone-1-methide

Herein, the first allylsilane reagent-controlled divergent asymmetric Hosomi–Sakurai conjugate allylation and hetero-Diels–Alder (HDA) with 2-naphthoquinone-1-methide (2-Nap-Q-1-M) under the catalysis of Sc^III/Feng ligand complex is reported. With these methods, a variety of uniquely substituted chiral allyl-functionalized diaryl compounds and naphthopyran products were obtained in a straightforward and highly stereoselective (up to 96.5:3.5 e.r.) manner under mild conditions. Moreover, it is demonstrated that 2-Nap-Q-1-M can serve as an efficient diene for a side asymmetric Diels–Alder (D-A) reaction. This principle can provide a straightforward access to hydrophenalene in an optically active form, which represents a structural core of various natural products and bioactive molecules.     

Synthesis of Six-Membered Functionalized Carbocyclic Compounds by One-Pot Reaction of Hydroquinone Derivatives and Dienes

A general method for one-pot reaction of hydroquinone derivatives and dienes has been developed. The system of Pb₃O₄ in tetrahydrofuran–trifluoroacetic acid was found to play dual roles as oxidant for the generation of quinones in situ and as catalyst for the Diels–Alder cycloaddition, which makes the one-pot reaction efficient and easy to carry out. Using this method, a variety of six-membered functionalized carbocyclic compounds can be easily prepared in medium to excellent yields at room temperature.      

Straightforward and Facile Synthesis of a Bioactive Component from Zingiber cassumunar Roxb.

Straightforward and facile synthesis of a bioactive component A from Zingiber cassumunarRoxb. is described. The phenylbutenoid dimer A was reported to possess anti-inflammatory and cytotoxic activities. The optically active cyclohexene ring fragment was obtained via the highly diastereo- and enantioselective Diels–Alder reaction of chiral acryloyloxazolidinones (1a and 1b) and 1-(4-hydroxy-3-methoxyphenyl)butadiene (2). The enantiomeric excess of Diels–Alder adducts 3a and 3bwere determined via high-performance liquid chromatotography of the corresponding bis-acetate (6). The greatest enantiomeric excess (99.9% ee) was obtained when the 4-phenyloxazolidin-2-one (1a) chiral auxiliary was used in combination with TiCl4. The optically pure bioactive compound A was prepared from the optically active Diels–Alder adduct (3a) in two additional steps.     

Synthesis of Functionalized p-Phenylene Oxide Oligomers

Oligomers of p-phenylene oxides have been synthesized by coupling of substituted phenols and aryl bromides in the presence of cuprous chloride. The chain length varies from 2 to 5 phenyl rings functionalized at one end by an OH and OMe group and at the other end by an OH, OMe or NO₂ functions. The oligomers could be used in material science and as building blocks in supramolecular chemistry. Methods for chemoselective demethylation of methoxy groups were developed.     

Synthesis of 2‐Spironaphtho[2,3‐b]pyranoquinones

A convenient procedure for the synthesis of 2‐spirobenzopyranoquinone 5 and its application to the preparation of spironaphtho[2,3‐b]pyranoquinones 6 and 7 is described.     

Overcoming Thermodynamically Driven Retro-Diels–Alder Reaction through a Cascade One-Pot Process Exemplified for a Bio-Based Platform Chemical

In this contribution, we describe a new approach to apply thermodynamically unfavored reactions in synthetic chemistry and to integrate them in cascade processes. By means of a new developed procedure for multi-step one-pot syntheses, we succeeded in nearly completely converting a thermodynamically labile Diels–Alder adduct, which strongly tends to react back, to the target product with high conversion of >99 % and in excellent yield by coupling with a rapid subsequent hydrogenation reaction. In detail, the process is based on the use of a rotating reaction vessel to form a thin product film of the thermodynamically labile Diels–Alder product from 2-methylfuran and maleic acid anhydride (as two bio-based raw materials), which then slowly dissolves into solution and is immediately converted by hydrogenation to the target product. Such a combination of Diels–Alder reaction and hydrogenation in a sequential one-pot process without by-product formation enables the efficient production of the product, which represents a valuable bio-based platform chemical. In addition, this process concept generally opens a perspective for the integration of thermodynamically unfavorable reaction steps in multi-step one-pot cascade processes while obtaining the desired target products in high yields.