Synthesis of a versatile functionalized tetraquinane. Convenient access to 1,3-bishomopentaprismanedione

The tetracyclic diene dione 1 has been synthesized by a short oxidative decarboxylation route starting with the domino Diels-Alder adduct 2. Photocyclization of the bisketal of 1 was used to arrive expediently at 1,3-bishomopentaprismanedione (7).     

Oxidative Diels-Alder reaction of 2, 5-dihydroxybenzoic acid with 1, 3-cyclopentadiene

The electrochemical oxidation of 2,5-dihydroxybenzoic acid (1) has been studied in the presence of 1,3-cyclopentadiene (2) as a diene in water/ethanol (40/60, v/v) mixture using cyclic voltammetry and controlled-potential coulometry. A plausible mechanism for the oxidation of 1 in the presence of 2 is presented. Compound 1 was converted into bis-adduct 5 via electrooxidation, Diels-Alder reaction of 2 to anodically generated 3,6-dioxocyclohexa-1,4-dienecarboxylic acid (1ox), decarboxylation reaction, electrooxidation and Diels-Alder reaction. The electrochemical synthesis of 5 was performed in a onepot reaction, without toxic reagents, at a carbon electrode in a simple cell using an environmentally friendly method.     

Synthesis and diels-alder reactions of e-1-trimethylsilylbuta-1,3-diene

A novel synthesis of E-1-trimethylsilylbuta-1,3-diene (1) has been achieved, and its Diels-Alder reactions with maleic anhydride, diethyl maleate, dimethyl fumarate, methyl propiolate, acrolein and acrylonitrile have been investigated. The structures of the products were studied to determine the stereoselectivity and regioselectivity of the reactions of this diene. In all cases with monosubstituted dienophiles the silyldiene 1 afforded the 1,3-disubstituted isomer (meta isomer) as the predominate regioisomer.     

Polymer-supported electron-rich diene for hetero Diels-Alder reactions

A Brassard diene analogue was grafted on a modified Merrifield resin and used in a hetero Diels-Alder reaction with various aldehydes or ketones. The reaction gave access to 6-substituted 5,6-dihydropyrones (5a-u). This new immobilized electron-rich diene is more stable than the corresponding native diene, and is a versatile supported reagent.     

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.     

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.     

Synthetic studies on siccanin. Efficient construction of the cis-fused drimane unit and synthesis of isosiccanin methyl ether

Under ferric chloride catalysis, the Diels-Alder addition of dienone ester 3 to diene 4 occurred readily to give adduct 5 which possesses the complete carbon framework of the sesquiterpene unit of siccanin (1) with the correct relative stereochemistry. Further elaboration on 5 gave rise to the methyl ether of isosiccanin (2), an unnatural diastereomer of the antifungal antibiotic 1.     

On the conversion of 1-glutamate to 1-dopa : The preparation and chemistry of 1-methoxy-2-acetoxy-3-trimethylsilyloxy-1,3-butadiene

The title diene was prepared by the enol silylation of 1-methoxy-2-acetoxybut-1-ene-3-one. It undergoes Diels-Alder cycloaddition with a variety of dienophiles. Through such cycloaddition ther is provided acess to regiospecifically monoderivatized diosphenols and catechols. Cycloaddition of the title compound with dienophile (28), derived from L-glutamate, provides a route to optically pure L-Dopa.     

One-pot enyne metathesis/Diels-Alder reaction for the construction of highly functionalized novel polycyclic aza-compounds

Various tricyclic dienes were synthesized via enyne metathesis using the first generation Grubbs catalyst. The enyne metathesis proceeded smoothly in refluxing CH₂Cl₂ with a low catalyst loading (3.0 mol %), giving good yields (72-89%) of the tricyclic products 6 and 16. The resulting 1,3-dienes are suitable precursors of polycyclic structures via a Diels-Alder process. One-pot RCM/Diels-Alder reactions of the enyne products with dienophiles proceeded smoothly to afford polycyclic compounds as a single cycloadduct. The structures of the Diels-Alder adducts were determined by ¹H NMR spectra and X-ray analysis. The cycloadducts were formed via the approach of the dienophiles towards the diene in endo mode.     

An efficient enantiocontrolled synthesis of (+)-4-demethoxydaunomycinone

A chromatography-free, seven-step synthesis of the title compound (3) is described. The tetracyclic carbon skeleton is elaborated by a Diels-Alder strategy in which the 6a,7- and 1O.1Oa-bonds are constructed the epoxy-tetrone (9) and the D-glucose-derived diene (10b) serving as precursors. Interestingly, the cycloaddition reaction leads mainly to the “desired” cycloadduct (11b), revealing a notable diastereofacial reactivity of the diene (10b). Hydrolysis of the cycloadduct (11b) leads to the epoxy-pentone (12b) which is reduced to the dihydroxy-trione (13b). The reaction of the last-cited compound with ethynylmagnesium bromide affords a mixture of the ethynyl-diones (20b) and (21b), the latter compound arising from the precursor (13b) by a prior epimerisation at the 10a-position. The mixture of ethynyldiones (20b) and (21b) is converted into the anthracycline (14b) by the action of lead (IV) acetate. By a hydrolysis-hydration sequence, the anthracycline (14b) is transformed into (+)-4-demethoxydaunomycinone (3).     

Generation and reactions of new ether and acetal functionalized tricyclo[3.3.0.0]oct-1(5)-ene derivatives. DSC and NMR studies on the [2+2] retrocycloaddition of several cyclobutane dimers

Two new highly pyramidalized tricyclo[3.3.0.0^3,7]oct-1(5)-ene derivatives containing ether and acetal functionalities have been generated, trapped as Diels-Alder adducts and dimerized. The initially obtained diene dimers were photochemically converted into cyclobutane derivatives. The thermal reversion of several cyclobutane derivatives to the corresponding dienes has been studied by ¹H NMR, ab initio calculations and DSC. For the first time, transannular additions of bromine and iodine to a diene dimer of this series have been observed.     

Regarding the structure of [2.2](2,6,2',7')-naphthalenophane-1,11-diene and its conformational mobility

The synthesis of [2.2](2,6,2',7')naphthalenophane -1,11 - diene 4 has been effected by pyrolysis of the bis-sulphoxide 10, in turn prepared by a ring-contraction procedure of the [3.3]dithiacyclophane 7. The diene 4 has been fully characterized by spectroscopic and chemical methods. The variable-temperature ¹H NMR spectra of the diene 4 indicated that the compound undergoes conformational flipping in solution and has a conformational energy barrier ΔG^≠_25°. 14.9 kcal mol^-1 and a coalescence temperature T_c 38° for the internal protons H_c and H_c' (at 100 MHz). These results differ from those previously recorded. A complete assignment of the pmr spectrum of the cyclophane diene 4 at 270 MHz is presented together with the spectrum of the corresponding saturated [2.2]cyclophane 3.     

Synthesis of (±)-kuwanon V and (±)-dorsterone methyl ethers via Diels-Alder reaction

The mulberry Diels-Alder adducts, the pentamethyl ethers of kuwanon V 1a and dorsterone 2a were synthesised via a biomimetic intermolecular [4+2] cycloaddition reaction between a highly electron-rich dienophile and a Lewis acid sensitive diene derived from chalcone. Cycloaddition under thermal conditions afforded 1a and 2a (in 3:2 ratio). Cycloaddition catalysed by AgOTf/Bu₄NBH₄ gave higher yields of the adducts.     

Diels-Alder cycloaddition of 2-azadienes to methyl 2-(2,6-dichlorophenyl)-2H-azirine-3-carboxylate in the synthesis of methyl 4-oxo-1,3-diazabicyclo[4.1.0]heptane-6-carboxylates

A number of fused 4-oxo-1,3-diazabicyclo[4.1.0]heptane-6-carboxylates, a new type of compound, have been obtained by Diels-Alder cycloaddition between nucleophilic 2-azadienes and an electrophilic 2H-azirine. The reactions are completely endo- and regioselective, the azirine being added by its less hindered face to the diene. There are two isomers 7 and 8 formed from dienes 1 due either to isomerization of the cycloadducts 7 and 8 or by isomerization of the CN bond of the diene during the reaction. The isomer 10 is formed from diene 2e, and a single diastereoisomer structure 4a-i is formed from dienes 11. Some pyrimidones 8a, 7c/8c, 7e, 10, 11d have been hydrolyzed leading to functionalised aziridines 12, 13 and 15.     

The Diels-Alder Reaction of 2,3-Disulfur-Substituted 1,3-Butadienes

The 2,3-disulfur-substituted 1,3-dienes (1) can be readily prepared from their stable 3-sulfolene precursors (2) by thermal extrusion of SO₂. The Diels-Alder reaction of diene (1) with several dienophiles has been studied. The substituent effect on the reactivity and regioselectivity follows the order of PhS >PhSO >PhSO₂. Lewis acid can greatly increase the regioselectivity of this reaction. The diene (1c), bearing a strong electron-withdrawing sulfonyl group, also reacted as a dienophile.     

Highly enantioselective Diels-Alder reactions of Danishefsky type dienes with electron-deficient alkenes catalyzed by Yb(III)-BINAMIDE complexes

1-Methoxy-3-trimethylsiloxy-1,3-butadiene (Danishefsky's diene) is recognized as a synthetically useful diene due to its high reactivity in the Diels-Alder reaction with electron-deficient alkenes to give oxygen-functionalyzed cyclohexenes and substituted cyclohexenones, which are important building blocks for the total synthesis of natural products. However, the development of catalytic enantioselective versions of Diels-Alder reactions using Danishefsky type dienes with electron-deficient alkenes has been difficult because of the instability of the dienes under Lewis acidic conditions. Only highly reactive CO and CN double bonds are employed in a hetero-Diels-Alder reaction which proceeds under catalysis of chiral Lewis acids. We have developed a new chiral ligand, BINAMIDE, which is easily prepared from 1,1'-binaphtyl-2,2'-diamine by acylation. The highly diastereo- and enantioselective Diels-Alder reaction of Danishefsky type dienes with electron-deficient alkenes in the presence of an Yb(III)-BINAMIDE complex has been developed. The reaction proceeded in an exoselective mode and gave chiral highly functionalized cyclohexene derivatives in good yields.     

Microwave-assisted reactions of nitroheterocycles with dienes. Diels-Alder and tandem hetero Diels-Alder/[3,3] sigmatropic shift

Diels-Alder cycloaddition of 3-nitro-1-(p-toluenesulfonyl)indole 1 with dienes 2-6 under microwave irradiation in solvent-free conditions gave carbazole derivatives after elimination of the nitro group and in situ aromatization. While 3-nitro-1-(p-toluenesulfonyl)pyrrole 11 afforded indole derivatives, 4-nitro-1-(p-toluenesulfonyl)pyrazole 13 with cyclohexadiene 2 did not afford the expected cycloadduct but instead gave 1-cyclohexen-2-ylpyrazole 16. This process occurred by hydrolysis of the 1-(p-toluenesulfonyl) group, protonation of the diene and nucleophilic addition of the pyrazolate ion, as elucidated by computational studies. Reaction of nitroindole 1 with cyclohexadiene 2 afforded exclusively the endo stereoisomer (10endo) in a tandem hetero Diels-Alder/[3,3] sigmatropic shift, as determined by computational calculations.     

Naphtho[1,2-c:5,6-c]difuran: a reactive linker and cyclophane precursor

Naphtho[1,2-c:5,6-c]difuran has been isolated in a 9-step synthesis from 2,6-dimethylnaphthalene. It is a highly reactive diene similar in nature to the related isobenzofuran. In Diels-Alder reactions, its intermediate monoadducts are actually less reactive that the parent difuran making possible sequential Diels-Alder reactions with different dienophiles. Reaction with a tethered bis(dienophile) leads to the production of a naphthalenic cyclophane.     

Scalable synthesis of highly reactive 1,3-diamino dienes from vinamidinium salts and their use in Diels-Alder reactions

A practical and chromatography-free synthesis of vinamidinium salts and their use as diene precursors in Diels-Alder reactions is reported. Additionally, 1,3-dipyrrolidino-1,3-butadiene was shown to be significantly more reactive than Rawal's diene in a competition experiment.     

High-pressure mediated Diels-Alder reaction of di-l-menthyl acetoxy-methylenemalonate with furan: Enantioselective synthesis of β-D-ribofuranosylmalonate,a prospective synthon for C-nucleoside

β-D-Ribofuranosylmalonate [D]-4 has been synthesized through high-pressure Diels-Alder reaction of furan with di-l-menthyl acetoxymethylenemalonate (1b), followed by reductive retrograde aldol CC bond fission. A mechanism accounting for the observed diastereoselectivity in the Diels-Alder reaction is proposed.