Thermal Reactions of Guaiazulene and Its 3-Methyl Derivative with Dimethyl Acetylenedicarboxylate

The thermal reaction of 7-isopropyl-1,3,4-trimethylazulene (3-methylguaiazulene; 2 ) with excess dimethyl acetylenedicarboxylate (ADM) in decalin at 200° leads to the formation of the corresponding heptalene- ( 5a/5b and 6a/6b ; cf. Scheme 3) and azulene-1,2-dicarboxylates ( 7 and 8 , respectively). Together with small amounts of a corresponding tetracyclic compound (‘anti’- 13 ) these compounds are obtained via rearrangement (→ 5a/5b and 6a/6b ), retro-Diels-Alder reaction (→ 7 and 8 ), and Diels-Alder reaction with ADM (→ ‘anti’- 13 ) from the two primary tricyclic intermediates ( 14 and 15 ; cf. Scheme 5) which are formed by site-selective addition of ADM to the five-membered ring of 2 . In a competing Diels-Alder reaction, ADM is also added to the seven-membered ring of 2 , leading to the formation of the tricyclic compounds 9 and 10 and of the Diels-Alder adducts ‘anti’- 11 and ‘anti’- 12 , respectively of 9 and of a third tricyclic intermediate 16 which is at 200° in thermal equilibrium with 9 and 10 (cf. Scheme 6). The heptalenedicarboxylates 5a and 5b as well as 6a and 6b are interconverting slowly already at ambient temperature (Scheme 4). The thermal reaction of guaiazulene ( 1 ) with excess ADM in decalin at 190° leads alongside with the known heptalene- ( 3a ) and azulene-1,2-dicarboxylates ( 4 ; cf. Schemes 2 and 7) to the formation of six tetracyclic compounds ‘anti’- 17 to ‘anti’- 21 as well as ‘syn’- 19 and small amounts of a 4:1 mixture of the tricyclic tetracarboxylates 22 and 23 . The structure of the tetracyclic compounds can be traced back by a retro-Diels-Alder reaction to the corresponding structures of tricyclic compounds ( 24--29 ; cf. Scheme 8) which are thermally interconverting by [1,5]-C shifts at 190°. The tricyclic tetracarboxylates 22 and 23 , which are slowly equilibrating already at ambient temperature, are formed by thermal addition of ADM to the seven-membered ring of dimethyl 5-isopropyl-3,8-dimethylazulene-1,2-dicarboxylate ( 7 ; cf. Scheme 10). Azulene 7 which is electronically deactivated by the two MeOCO groups at C(1) and C(2) shows no more thermal reactivity in the presence of ADM at the five-membered ring (cf. Scheme 11). The tricyclic tetracarboxylates 22 and 23 react with excess ADM at 200° in a slow Diels-Alder reaction to form the tetracyclic hexacarboxylates 32 , ‘anti’- 33 , and ‘anti’- 34 (cf. Schemes 10–12 as well as Scheme 13). A structural correlation of the tri- and tetracyclic compounds is only feasible if thermal equilibration via [1,5]-C shifts between all six possible tricyclic tetracarboxylates ( 22, 23 , and 35–38 ; cf. Scheme 13) is assumed. The tetracyclic hexacarboxylates 32 , ‘anti’- 33 , and ‘anti’- 34 seem to arise from the most strained tricyclic intermediates ( 36–38 ) by the Diels-Alder reaction with ADM.     

Thermal Reaction of Highly Alkylated Azulenes with Dimethyl Acetylenedicarboxylate: HOMO(Azulene) vs. SHOMO(Azulene) Control in the Primary Thermal Addition Step

The reaction of highly alkylated azulenes with dimethyl acetylenedicarboxylate (ADM) in decalin or tetralin at 180–200° yields, beside the expected heptalene- and azulene-1,2-dicarboxylates, tetracyclic compounds of type ‘anti’- V and tricyclic compounds of type E (cf. Schemes 2–4 and 8–11). The compounds of type ‘anti’- V represent Diels-Alder adducts of the primary tricyclic intermediates A with ADM. In some cases, the tricyclic compounds of type E also underwent a consecutive Diels-Alder reaction with ADM to yield the tetracyclic compounds of type ‘anti’- or ‘syn’- VI (cf. Schemes 2 and 8–11). The tricyclic compounds of type E , namely 4 and 8 , reversibly rearrange via [1,5]-C shifts to isomeric tricyclic structures (cf. 18 and 19 , respectively, in Scheme 6) already at temperatures > 50°. Photochemically 4 rearranges to a corresponding tetracyclic compound 20 via a di-π-methane reaction. The observed heptalene- and azulene-1,2-dicarboxylates as well as the tetracyclic compounds of type ‘anti’'- V are formed from the primary tricyclic intermediates A via rearrangement (→heptalenedicarboxylates), retro-Diels-Alder reaction (→ azulenedicarboxylates), and Diels-Alder reaction with ADM. The different reaction channels of A are dependent on the substituents. However, the main reaction channel of A is its retro-Diels-Alder reaction to the starting materials (azulene and ADM). The highly reversible Diels-Alder reaction of ADM to the five-membered ring of the azulenes is HOMO(azulene)/LUMO(ADM)-controlled, in contrast to the at 200° irreversible ADM addition to the seven-membered ring of the azulenes to yield the Diels-Alder products of type E . This competing reaction must occur on grounds of orbital-symmetry conservation under SHOMO(azulene)/LUMO(ADM) control (cf. Schemes 20–22). Several X-ray diffraction analyses of the products were performed (cf. Chapt. 4.1).     

Diels-Alder Reactions of (1H-Indol-3-yl)-enacetamides and -endiacetamides: A Selective Access to Acetylamino-Functionalized [b]Annelated Indoles and Carbazoles

Diels-Alder reactions of the (1H-indol-3-yl)-enacetamides and -endiacetamides 1a – d with some carbodieno-philes and 4-phenyl-3H-1,2,4-triazole-3,5(4H)-dione give rise to the novel amino-functionalized carbazole; 4 – 6 and 8 (Scheme 3). Ethenetetracarbonitrile reacts with 1b to furnish the Michael-type adduct 7 (Scheme 3). Structural aspects of the starting materials 1 , which exhibit above all 3-vinyl-1H-indole reactivity, are discussed with regard to the prediction of a Diels-Alder process.     

Herstellung neuer polycyclischer Verbindungen durch intramolekulare Diels-Alder-Reaktionen von Cyclohexa-2,4-dien-1-on-Abkömmlingen

Synthesis of new polycyclic compounds by means of intramolecular Diels-Alder reactions of cyclohexa-2,4-dien-1-one derivatives Thermal rearrangement of mesityl penta-2,4-dienyl ether ( 1 ), consisting of the isomers E (93%) and Z (7%), furnished, besides mesitol, the two mesityl penta-1,3-dienyl ethers 2 (24%) and 3 (3%), and the two tricyclic ketones 4 (4,5%) and 5 (12,5%) (Scheme 1). A probable mechanism for this formation of 2 involves a [1,5]-hydrogen shift in (Z)- 1 . Isomerisation of (E)- 1 to (Z)- 1 at 145° occurs via reversible sigmatropic [3,3]- and [5,5]-rearrangements of (E)- 1 to the cyclohexadienones 38 and 39 respectively (see Chapter A p. 1710, and Scheme 15). Formation of 3 from either (Z)- 1 or 2 is rationalized by a series of pericyclic reactions as outlined in Chapter A and Scheme 16. The tricyclic ketones 4 and 5 are undoubtedly formed by internal Diels-Alder reactions of the 6-pentadienyl-cyclohexa-2,4-dien-1-one 6 (Scheme 2). In fact, at 80° 6 is converted into 4 (5%) and 5 (35%). At 80° the cyclohexadienone derivative 7 furnished the corresponding tricyclic ketones 8 (15%) and 9 (44%) (Scheme 2). 5 and 9 contain a homotwistane skeleton. 8 and 9 are easily prepared by reaction of sodium 2,6-dimethylphenolate with 3-methyl-penta-2,4-dienyl bromide at ambient temperature, followed by heating, and finally separation by cristallization and chromatography. The cyclohexadienones 6 and 7 have mainly (E)-configuration. Here too (E) → (Z) isomerization is a prerequisite for the internal Diels-Alder reaction, and this partly takes place intramolecularly through reversible Claisen and Cope rearrangements (Scheme 17). On the other hand, experiments in the presence of 3,5-d₂-mesitol have shown (Table 1) that intermolecular reactions, involving radicals and/or ions, are also operating (see Chapter B , p. 1712). Two different modi (I and II) exist for intramolecular Diels-Alder reactions (Scheme 18). Whereas only modus I is observed in the cyclization of 5-alkenyl-cyclohexa-l,3-dienes, in that of (2)-cyclohexadienones 6 and 7 (Scheme 2) both modi are operating. Only in modus 11-type transitions is the butadienyl conjugation of the side chain retained, so that modus 11-type addition is preferred (Chapter C p. 1716). Analogously to the synthesis of the tricyclic ketones 4 , 5 , 8 and 9 , the tricyclic ketone 15 (Scheme 4) and the tetracyclic ketone 11 (Scheme 3) are prepared from mesitol, pentenyl bromide and cycloheptadienyl bromide, respectively. From the polycyclic ketones derivatives such as the alcohols 16 , 17 , 18 , 19 , 23 , 24 and 25 (Schemes 9 and 11), policyclic ethers 20 , 21 , 22 and 26 (Scheme 10), epoxides 30 , 32 (Scheme 13), diketones 31 , 33 (Scheme 13) and ether-alcohols 35 and 36 (Scheme 14) have been prepared. Most of these conversions show high stereoselectivity.     

Synthese von Triafulven-Vorstufen für Retro-Diels-Alder-Reaktionen

Synthesis of Triafulvene Precursors for Retro-Diels-Alder Reactions Triafulvene precursors exo? 15 and endo? 15 have been prepared by addition of dibromocarbene to benzobarrelene 12 followed by a lithium-halogen exchange, methylation, and elimination of HBr ( 12→13→14→15 ), (Scheme 2). Gas-phase pyrolysis of exo/endo-mixtures of 15 above 400° gave minor amounts of naphthalene ( 16 ), traces of a hydrocarbon C₄H₄ identified by MS (presumably triafulvene 1 ) and predominantly (36%) the isomerization product 17 (Scheme 3). In a second synthetic approach the well-known cycloheptatriene-norcaradiene equilibrium of type 26?27 has been utilised to prepare various endo-trans-3-(X-methyl) tricyclo[3.2.2.0^2,4]nona-6,8-dienes 31 (Scheme 5). However, numerous elimination experiments 31→9 failed so far. The structure of two rearrangement products 33 and 34 (Scheme 6) has been elucidated.     

Hetero-Diels-Alder-Reaktion mit 1,3-Thiazol-5(4H)-thionen

Hetro-Diels-Alder Reaction with 1,3-Thiazol-5(4H)-thiones On heating in toluene to 180° and on treatment with BF₃·Et₂O in CH₂Cl₂ room temperature, 1,3-dienes react with the C?S group of 1,3-thiazol-5(4H)-thiones 1 in a reversible Diels-Alder reaction to give spiro[4.5]-heterocycles of type 6. A 1:1 mixture of two regioisomeric cycloadducts is formed in the thermal reaction with 2-methylbuta-1,3-diene (isoprene, 5b ). In contrast, the formation of one regioisomer is strongly preferred in the BF₃-catalyzed reaction. Frontier-orbital control as well as steric factors seem to be responsible for the observed regioselectivity. BF₃-Catalyzed, cyclic 1,3-dienes and 1 also undergo a smooth Diels-Alder reaction. Whereas cyclohexa-1,3-diene ( 5c ) reacts with 1a and 1b to give a single isomer (presumably the ‘exo’-adduct), cyclopenta-1,3-diene ( 5d ) leads to a ca. 3:1 mixture of ‘exo’-and ‘endo’-isomer.     

Diels-Alder-Reaktionen mit 3-Cyclopropylidenprop-1-enyl-ethyl-ether als 1,3-Dien

Diels-Alder Reactions with 3-Cyclopropylideneprop-1-enyl Ethyl Ether as 1,3-Diene The title compound undergoes readily Diels-Alder reactions with various dienophiles, especially with quinones. The resulting adducts constitute key intermediates in the synthesis of labdane diterpenoids.     

Highly Stereoselective Total Syntheses of (±)-Chelidonine and of (±)-Norchelidonine by an Intramolecular o-Quinodimethane/Nitrostyrene-Cycloaddition

Conversion of 2-bromomethylstyrene 22 and benzocyclobutenyl carbamate 28 to the benzophenanthridine alkaloids (±)-chelidonine ( 1 , five steps, 25% from 28 ) and to (±)-norchelidonine ( 2 , six steps, 24% from 28 ) are described. The key step 29 → 31 involves a highly regio- and stereocontrolled intramolecular Diels-Alder reaction of the (E)-quinodimethane 30 .     

Cycloaddition of Carbodiimides with a Heteroaromatic Substituent to Allenic Acids

Cycloaddition of the allenic acid 3 with the N -cyclohexyl-N′ -heteroaromatic carbodiimides 2a and 2b gave the isomeric pyrido[1,2-a]pyrimidinones 4 and 5 and thiazolo[3,2-a]pyrimidinones 6 and 7 , respectively, instead of the expected Diels-Alder adducts analogous to 1 . The compounds of the latter type, i.e. 8 and 9 , were formed from 3 and carbodiimides 2c and 2d , respectively, containing an N′-(pyrazin-2-yl) or N′-(pyrimidin-2-yl) substituent.     

Thermal and Photochemical Reactions of 1,2-Annelated Barrelenes and Hydrobarrelenes in the presence of transition-metal carbonyls

The [Co₂(CO)₈]-mediated retro-Diels-Alder reaction of the annelated barrelenes 1 afforded the 1H-indol-2(3H)-one derivatives 3 (Scheme 1), while the hydrobarrelene 4a , under the same conditions, was converted to the anilide 6 (Scheme 2); 4b remained unaffected. The direct irradiation of 1 led to the annelated cyclooctatetraenes 7 (Scheme 3). On irradiation in the presence of excess of [Fe(CO)₅], 1a , 1b , and 4a gave the tricarbonyliron complexes 8 , 9 , and 11 , respectively (Schemes 3 and 4); under these conditions, 4b was inert.     

Copper(I)- and Copper(II)-catalyzed Diels-Alder Additions of α-Substituted Acrylonitrile to Furan. The Synthesis of 7-Oxa-bicyclo[2.2.1]hept-5-en-2-one

The difficult Diels-Alder additions of α-acetoxy- and α-chloroacrylonitrile to furan can be run at 20–35° and atmospheric pressure in the presence of CuCl. Cu(BF₄) · 6 H₂O, Cu(OOCCH₃)₂ · H₂O or cupric tartrate · 3H₂O. Under kinetic control, the exo-carbonitrile adducts 2 and 8 , respectively, are favoured. Saponification of the 2endo-acetoxy-7-oxabicyclo[2.2.1]hept-5-ene-2exo-carbonitrile ( 2 ) furnished the 7-oxabicyclo[2.2.1]hept-5-en-2-one ( 4 ). Basic hydrolysis of the adducts ( 8 + 9 ) of α-chloroacrylonitrile to furan and its 5exo, 6exo-isopropylidenedioxy derivatives did not give the corresponding ketones, the carboxamides 14 + 15 and 16 + 17 , respectively, were isolated.     

Design and Synthesis of a Potential Dopamine D-1 Antagonist

The diastereoselective synthesis of (±)-trans-transoid-7-bromo-8-hydroxy-1-methyl-1,2,3,4,4a,5,10,10a-octahydro-10-phenylbenzo[g]quinoline ( 8 ) is described, using an intramolecular Diels-Alder reaction and a reductive cyclisation for piperidine ring-formation as key steps. Compound 8 was prepared as a putative D-1 receptor antagonist which contains (2,2-diphenylethyl)amine as a partial structure.     

Cycloaddition of 2H-Pyran-2-thiones with Nitroso Derivatives. An Unexpected Cycloaddition-Rearrangement Reaction

Reaction of pyran-2-thiones 4 with nitroso derivatives led surprisingly to type- 8 ( 19 ) adducts which proved to be isomeric with the initially expected primary Diels-Alder cycloadducts 5 . Methyl 2-thioxo-2H-pyran-5-carboxylate ( 4f ), when reacted with nitrosobenzene at -10°, led quantitatively to the thieto-oxazine intermediate 13 , which turned out to be the cornerstone of the complex cycloaddition-rearrangement 5 → 8 reaction pathway (Scheme 3). Differential scanning calorimetry, as performed for the 18a → 19a conversion, permitted to demonstrate that this multistep rearrangement is overall a higly exothermal process, the final product 19 representing an energy-sink along this reaction pathway.     

Chemie der Cumalinsäurederivate. I. Synthese und Diels-Alder-Reaktionen von 1-Arylamino-2-methoxycarbonylbutadienen

The nucleophilic attack of substituted anilines at position 6 of methyl coumalate (1) opens the α-pyrone ring to form 4-arylamino-3-(methoxycarbonyl)butadien-1-carboxylic acid 2 (Scheme 1). The latter are easily decarboxylated at room temperature in polar aprotic solvents to 1-arylamino-2-(methoxycarbonyl)butadiene 4 which smoothly undergo regio- and stereospecific Diels-Alder reactions with different dienophiles.     

(Benzylthio)- und (Arylthio)-substituierte Nitril-ylide: Thermische Erzeugung und Reaktionen

Thermal Generation and Reactions of (Benzylthio)-and (Arylthio)-Substituted Nitrile Ylides Thermolysis of 4-(benzylthio)- and 4-(arylthio)-1,3-oxazol-5(2H)-ones 6 , at 110–155° in the presence of dipolarophiles with activated C≡C, C?C, C?O, C?S, and N?N bonds, led to 5-membered cyclo-adducts and CO² (cf. Schemes 3, 5-7). Heating 6a and 6c in the presence of ethyl propiolate yielded ethyl quinoline-3-carboxylate ( 19 ) and ethyl pyridine-3-carboxylate( 22 ), respectively (cf. Scheme 8). These results are rationalized on the basis of the intermediate formation of thio-substituted nitrile ylides of type 7 (cf. Scheme 2), which undergo regioselective 1,3-dipolar cycloadditions with reactive dipolarophiles. In the absence of such a dipolarophile, the nitrile ylides isomerize via a [1,4]-H shift to give 2-aza-1,3-butadienes of type 20 . The latter are trapped in a Diels-Alder reaction with ethyl propiolate (cf. Scheme 8).     

1,3-Butadienyl-thiocyanate in der Diels-Alder-Reaktion mit anschliessender [3,3]-sigmatroper Umlagerung

1,3-Butadienyl Thiocyanates in the Diels-Alder Reaction Followed by a [3,3]-Sigmatropic Shift (E)- and (Z)-1,3-Butadienyl thiocyanates 3 , 4 , and 12–15 have been synthesized selectively. Their use as dienes for Diels-Alder reactions followed by a [3,3]-sigmatropic shift to obtain an isomeric isothiocyanate has been studied. The butadienyl thiocyanates are, unfortunately, not very reactive in Diels-Alder reactions. This disadvantage can be overcome, if a trapping reaction with EtOH is added to the two-step sequence. This sequence allows to get good yields of the O-ethyl thiocarbamates 18–23 , even if the first two reactions have not favorable equilibrium constants.     

Total Asymmetric Synthesis of Doubly Branched Carba-hexopyranoses and Amino Derivatives Starting from the Diels-Alder Adducts of Maleic Anhydride to Furfuryl Esters

The Diels-Alder adducts of maleic anhydride to furfuryl esters were reduced into 7-oxabicyclo[2.2.1]hept-5-ene-1,2-exo,3-exo-trimethanol (±)- 15 and enantiomerically pure (−)- 15 (Scheme 1). The tripivalate of (±)- 15 was converted into (1RS,2RS,3RS,4RS,5SR,6SR)-1,5,6-tris(hydroxymethyl)cyclohexane-1,2,3,4-tetrol ((±)- 23 ; Scheme 2). Reaction of BBr₃ with the triacetate (±)- 30 of (±)- 15 gave (1RS,2RS,5RS,6RS)-5-bromo-6-hydroxycyclohex-3-ene-1,2,3-trimethyl triacetate ((±)- 31 ) at −78°, and (1RS,2RS,5SR,8SR)-2-endo-hydroxy-6-oxabicylo[3.2.1]oct-3-ene-5,8-dimethyl diacetate ((±)- 32 ) at 0° (Scheme 3). Single-crystal X-ray diffraction of (1RS,2RS,5SR,8SR)-2-acetoxy-6-oxabicyclo[3.2.1]oct-3-ene-5,8-dimethyl diacetate ((±)- 33 ) was carried out. Displacement of bromide (+)- 31 (derived from (−)- 15 ) with azide anion gave (+)- 38 which was transformed into (+)-(1R,2R,5S,6S)-5-amino-6-hydroxycyclohex-3-ene-1,2,3-trimethanol ((+)- 40 ) (Scheme 4). Reaction of (±)- 31 with BBr₃ at 0°, followed by azide disubstitution led to (1RS,2RS,5SR,6SR)-5-amino-3-(aminomethyl)-6-hydroxycyclohex-3-ene-1,2-dimethanol ((±)- 45 ). Dihydroxylation of (±)- 38 and further transformations gave (1RS,2RS,3SR,4RS,5SR,6RS)-5-amino-1,4,6-trihydroxycyclohexane-1,2,3-trimethanol ((±)- 49 ) and (1RS,2RS,3SR,4RS,5SR,6RS)-2,3-dihydroxy-7-oxabicyclo[4.1.0]heptane-2,3,4-trimethanol ((±)- 55 ) (Schemes 5 and 6). Expoxidation of the 4-nitrobenzoate (±)- 61 of (±)- 38 allowed the preparation of (1RS,2RS,3SR,4RS,5RS)-5-amino-1,4-dihydroxycyclohexane-1,2,3-trimethanol ((±)- 65 ) and of (1RS,2RS,3SR,4RS,5SR,6RS)-5-amino-4-hydroxy-7-oxabicyclo[4.1.0]heptane-1,2,3-trimethanol ((±)- 67 ) (Scheme 7). The new unprotected polyols and aminopolyols were tested for their inhibitory activity toward commercially available glycohydrolases. At 1 mM concentration, 34, 30, and 31% inhibition of β-galactosidase from bovine liver was observed for (+)- 40 , (±)- 65 , and (±)- 67 , respectively.     

Ru-Catalyzed Heptalene Formation from Azulenes and Dimethyl Acetylenedicarboxylate

It is shown that azulenes react with dimethyl acetylenedicarboxylate (ADM) in solvents such as toluene, dioxan, or MeCN in the presence of 2 mol-% [RuH₂(PPh₃)₄] already at temperatures as low as 100° and lead to the formation of the corresponding heptalene-1,2-dicarboxylates in excellent yields (Tables 1 and 2). The Ru-catalyzed reaction of ADM with 1-(tert-butyl)-4,6,8-trimethylazulene ( 31 ) takes place even at room temperature, yielding the primary tricyclic addition product 32 and its thermal retro-Diels-Alder product dimethyl 4,6,8-trimethylazulene-1,2-dicarboxylate ( 21 ; Scheme 4). At 100° in MeCN, 32 yields 90% of 21 and only 10% of the corresponding heptalene. These observations demonstrate that [RuH₂(PPh₃)₄] catalyzes the first step of the thermal formation of heptalenes from azulenes and ADM which occurs in apolar solvents such as tetralin or decalin at temperatures > 180° (cf. Scheme 1).     

Total Synthesis of the Gastroprotective Substance AI-77-B and of Analogues

The Diels-Alder adducts 8 of furan to 1-cyanovinyl acetate were converted into (Methyl 3-chloro)-5-O-(3-chlorobenzoyl)-2, 3-dideoxy-α-dl-arabino-hexofuranosid)uronic acid ((α)- 18a ) and into (methyl 3-azido-5-O-(3-chlorobenzoyl_-2,3-dideoxy-α-dl-ribo-hexofuranosid)uronic acid ((α)- 41a ). These compounds were condensed to (3S)-3-[(1′S)-1′-amino-3′-methylbutyl]-3,4-dihydro-8-hydroxyisocoumarin hydrochloride ((?)- 2 ); the resulting mixtures of diastereoisomeric amides were transformed and separated to give the gastroprotective substance AI-77- B ((?)- 1 ) and analogues.     

Ein neuer synthetischer Zugang zu Ubichinonen

A New Synthetic Route to Ubiquinones Ubiquinones 11 have been prepared employing a new strategy: as key step, the Diels-Alder reaction of 1,1,2-trichloroethene 3 with 2,5-bis[(trimethylsilyl)oxy]-3-methylfuran ( 2 ) has been used for the construction of the quinone part. After methanolysis of the [4 + 2] adducts 4a/4b , further reaction with cyclopentadiene and substitution of the Cl-atoms by MeO groups, the intermediate 7 is obtained. Diketone 7 can easily be alkylated with the desired polyprenyl side chain 9 (X = Br) using a strong base to yield, after a retro-Diels-Alder reaction, the corresponding ubiquinones 11 in high yields.