Die massenspektrometrische Retro-Diels-Alder-Reaktion: 1,2,3,4-Tetrahydrocarbazol. 30. Mitteilung über massenspektrometrische Untersuchungen

The mass spectral retro Diels-Alder-reaction: 1,2,3,4-tetrahydrocarbazole 1,2,3,4-Tetrahydrocarbazole undergoes a retro Diels-Alder-reaction under electron impact. C(2) and C(3) are eliminated as ethylene. This is shown by measuring the deuterated derivatives 1a , 1b and 1c . Furthermore the oxo-1,2,3,4-tetrahydrocarbazole derivatives 3 and 4 are investigated in respect to the mass spectral retro Diels-Alder reaction too.     

Diels-Alder-Reaktionen mit aktivierten 4-Methyl-1,3-pentadienen

Diels-Alder Reactions with Activated 4-Methyl-1,3-pentadienes Ethyl 4-methyl-1,3-pentadienyl ether, trimethyl[(4-methyl-1,3-pentadienyl)oxy]silane, and 1-(4-methyl-1,3-pentadienyl)pyrrolidine and the corresponding piperidine analogue have been used in Diels-Alder reactions with acrylonitrile, ethyl acetylenedicarboxylate, maleic anhydride, and 2,6-dimethyl-p-benzoquinone.     

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.     

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).     

Zur Lenkung der intramolekularen Diels-Alder-Reaktion von Cyclopentadienen mit olefinischen Substituenten

On the Course of the Intramolecular Diels-Alder-Reaction of Cyclopentadienes with Olefinic Substituents The 1:3 mixture of 4-bromobicyclo [3.2.0]hept-2-en-6-one and -7-one ( 1/2 ), available by N-bromosuccinimide bromination of bicyclo [3.2.0]hept-2-en-6-one, reacted rapidly with the organo-magnesium and -zinc reagents 3, 10a, 10b and 10d by cyclobutanone ring opening and bromide ion expulsion to give the 5-substituted cyclopentadienes 5, 12a, 12b/12c , and 12d as non-isolated intermediates. Further transformation occured in situ either by a direct intramolecular Diels-Alder reaction (path a) or by a [1,5]-H-migration prior to the intramolecular Diels-Alder reaction (path b). The intermediate 5 followed only path a to give the bridged norbornene derivative 7 , the intermediates 12a, 12b and 12c followed only path b to give the annellated norbornene derivatives 15a, 15b and 15c , respectively, and the intermediate 12d followed both paths to give the bridged 14d and the annellated norbornene derivative 15d (in the ration of about 1.4:1). These observations are discussed in terms of the relative velocities of [1,5]-H-migrations and intramolecular Diels-Alder reactions. The major conclusions are: (1) bridged norbornene derivatives with a six-membered ring C (such as 14d ) can be prepared by an intramolecular Diels-Alder reaction from 5-alkenyl-cyclopentadienes 12 , as long as the dienophilic double bond is activated by an appropriate substituent (as in 12d ); (2) such 5-alkenyl-cyclopentadienes 12 are available from the reaction of the bromo-bicyclo-heptenones 1/2 with suitable C-nucleophiles 10 .     

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.     

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.     

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.     

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 Approach to Highly Functionalized Tertiary α-Hydroxy Ketones: A Novel Route to the Hexahydrobenzofuran Portion of the Avermectins and Milbemycins

A highly regio- and stereoselective Diels-Alder reaction between dienophiles of type I and dienes of type II (Scheme 1) gives rise to Diels-Alder adducts of type III . Upon treatment with BF₃.Et₂O, these adducts are smoothly converted into the corresponding enones (Scheme 6). Under mild acidic conditions, enone (±)- 33 gave bicyclic diketone (±)- 34 via an intramolecular Michael-type addition. Diketone (±)- 34 has the correct relative configuration and a suitable ketone function at C(6) for further conversion into the hexahydrobenzofuran portion of the avermectins and milbemycins.     

Syntheses and tandem Diels-Alder reactivities of 7,7-diphenyl-[2.2.1]hericene (= 7-(diphenylmethylidene)-2,3,5,6- tetramethylidenebicyclo[2.2.1]heptane) and 7-oxa[2.2.1]hericene ( = 2,3,5,6-tetramethylidenebicyclo[2.2.1]heptan-7-one)

Syntheses of 7,7-diphenyl[2.2.1]hericene ( 4 ) and 7-oxa[2.2.1]hericene ( 5 ) are presented. Rate constants k₁ and k₂ of the two successive Diels-Alder additions of ethylenetetracarbonitrile (TCE) to 4 and to 5 have been evaluated. At 25° in toluene, the rate-constant ratio k₁/k₂ = 260 and 21 for 4 and 5 , respectively. These results are compared with those reported for the tandem Diels-Alder reactivity of 2,3,5,6-tetramethylidenebicyclo[2.2.1]heptane and other derivatives.     

Captodative olefins in normal and inverse Diels-Alder Reactions

Olefins with captodative substitution are reactive dienophiles in Diels-Alder reactions with normal and inverse electron demand. This is shown for reactions of 2-(tert-butylthio)acrylonitrile ( 1 ) with various dienes and heterodienes, e.g. 1,3-cyclohexadiene, hexachloro-1, 3-cyclopentadiene, acrolein, methacrolein, and methyl vinyl ketone (Schemes 2 and 3). In case of the hetrodienes, 3,4-dihydro-2H-pyrans are formed beside small amounts of tetrahydrothiophenes; however, with methyl vinyl ketone, both reaction pathways are equally followed. The high reactivity of captodative olefins in Diels-Alder reactions are rationalized on the basis of Sustmann's FMO model under consideration of Viehe's concept of captodative substitution of alkenes.     

Herstellung substituierter 1,6-Methano[10]annulene durch Cycloadditionsreaktionen des 1H-Cyclopropabenzols

Synthesis of Substituted 1,6-Methano[10]annulenes by Cycloadditions of 1H-Cyclopropabenzene Diels-Alder reactions of 1H-cyclopropabenzene ( 1 ) with electron-poor dienes, leading to substituted 1,6-methano[10]annulenes, are described.     

Control of the Diels-Alder-Addition Regioselectivity by Remote Olefins. Syntheses and Cycloadditions of 2,3,5-Trimethylidenebicyclo[2.2.1]heptane and 2,3,5,6,7-Pentamethylidenebicyclo[2.2.2]octane

The syntheses of 2,3,5-trimethylidenebicyclo[2.2.1]heptane ( 1 ) and 2,3,5,6,7-pentamethylidenebicyclo[2.2.2]-octane ( 2 ) are reported. The Diels-Alder additions of the diene moieties of these polyenes can be regioselective, probably because of a possible transannular interaction between the homoconjugated methylidene and s-cis-buta-diene groups.     

Synthese von Dimethyl-4a,8a-methanophthalazin-1,4-dicarboxylat und Derivaten

Synthesis of Dimethyl 4a,8a-Methanophthalazine-1,4-dicarboxylate and Derivatives Diels-Alder reaction with inversed electron demand of 1H-cyclopropabenzol 1 with dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate ( 2 ) yields dimethyl-4a,8a-methanophthalazine-1,4-dicarboxylate ( 3 ). The reactions of 3 with nucleophiles are also described.     

A Stereocontrolied Entry to Racemic Eremophilane and Valencane Sesquiterpenes via an Intramolecular Diels-Alder Reaction

A stereocontrolied route to racemic eremophilane and valencane sesquiterpenes is described via a common intermediate 15 , accessible from an intramolecular Diels-Alder reaction. ¹³ C - NMR .-shift assignments of the bicyclic intermediates and products are presented.     

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.     

Synthesis and Diels-Alder Reactivity of 1-(Dimethoxy)methyl-2,3,5,6-tetramethylidene-7-oxabicyclo[2.2.1]heptane. Preliminary communication

A short synthesis of the title compound 13 is reported. The acetal group in 13 enables one to control the regio- and stereoselectivity of the two successive Diels-Alder additions of the tetraene. The first addition is significantly faster than the second one, thus making 13 a versatile reagent for regio- and stereoselective ‘tandem’ cycloadditions.     

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 .     

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.