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.     

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.     

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 .     

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.     

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).     

Influence of Lewis Acids on the [4 + 2] Cycloaddition of N,N′-Fumaroylbis[(2R)-bornane-10,2-sultam] to Cyclopentadiene and application to various dienes

Among seventeen different Lewis acids, TiCl₄ was found to be the best catalyst for the [4 + 2] cycloaddition of cyclopentadiene to N,N′-fumaroylbis[(2R)-bornane-10,2-sultam] ((?)- 1 ). Independently of the TiCl₄ molar concentration, almost constant and complete (98–89% d.e.) diastereofacial π-selection was achieved in the Diels-Alder addition of (?)- 1 to cyclopentadiene, cyclohexadiene, isoprene, and 2,3-dimethylbuta-1,3-diene.     

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.     

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.     

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.     

Acid‐Induced Rearrangement of Cycloadducts from Cyclopropenecarboxylates and 1,3‐Diarylisobenzofurans

Treatment of several Diels–Alder adducts of cyclopropenecarboxylates and 1,3‐diarylisobenzofurans with a strong acid triggers a skeletal rearrangement resulting in 4,8b‐dihydro‐3aH‐indeno[1,2‐b]furans.     

Face Selectivity of the Diels-Alder Additions of Sulfur-Substituted Dienes and Tetraenes Grafted onto 7-Oxabicyclo[2.2.1]heptanes

Stereoselective synthesis of 2-methylidene-3-[(Z)-(2-nitrophenylsulfenyl)methylidene]-7-oxabicyclo[2.2.1]-heptane ( 16 ), 1,4-epoxy-1,2,3,4-tetrahydro-5,8-dimethoxy-2-methylidene-3-[(Z)-(2-nitrophenylsulfenyl)methylidene]anthracene ( 18 ), and 1,4-epoxy-1,2,3,4-tetrahydro-5,8-dimethyoxy-2-methylidene-3-[(Z)-(phenylsulfenyl)-methylidene]anthracene ( 19 ) are presented. The Diels-Alder additions of these S-substituted dienes and those of 2,5-dimethylidene-3,6-bis{[(Z)-(2-nitrophenyl)sulfenyl]methylidene}-7-oxabicyclo[2.2.1]heptane ( 17 ) have been found to be face selective and ‘ortho’ regiospecific. The face selectivity depends on the nature of the dienophile. It is exo-face selective with bulky dienophiles such as ethylene-tetracarbonitrile (TCNE) and 2-nitro-1-butene and endo-face selective with methyl vinyl ketone, methyl acrylate, and 3-butyn-2-one. In the presence of a Lewis acid, the face selectivity of the Diels-Alder reaction can be reversed. The addition of the first equivalent of a dienophile to tetraene 17 is at least 100 times faster than the addition of the second equivalent of the same dienophile to the corresponding mono-adduct. The X-ray structure of the crystalline bis-adduct 43 , a 7-oxabicyclo[2.2.1]hepta-2,5-diene system annellated to two cyclohexene rings, resulting from the successive additions of methyl acrylate and methyl vinyl ketone to tetraene 17 is presented. Only one of the two endocyclic double bonds of the 7-oxabicyclo[2.2.1]hepta-2,5-diene deviates from planarity, the substituents bending towards the endo face by 5.7°.     

Structure and Thermal Behaviour of Methylcyclopentadiene Dimers

The mixture of isomeric dimethyl-endo-tricyclo[5.2.1.0^2,6]deca-3,8-dienes ( A ) resulting from Diels-Alder reactions of 1-, 2-, and 5-methylcyclopenta-1,3-dienes ( i – iii , respectively) at 20° was shown by GLC analysis to consist of at least 10 components (Table 1). The structures of the six major isomers 1 – 6 , representing 96% of the total mixture, were established by ¹H- and ¹³C-NMR spectroscopy. Whereas on heating up to 110° the proportions of 1 , 2 , 4 , and 6 remain nearly unaffected (±2 %), the dimers 3 and 5 , formed in 22 % and 24 % yield, respectively, at 20°, isomerise above 70° reversibly via [3,3]-sigmatropic rearrangement and equilibrate at 110° to a ca. 10:1 ratio.     

Synthesis of Substituted 1-Thiocyanatobutadienes and their Application in a Diels-Alder/[3,3] Sigmatropic Rearrangement Tandem Reaction

Summary. The retrosynthetic analysis of Ibogamine, a natural psychotropic alkaloid with exceptional anti-addictive properties found in both enantiomeric forms, requires an efficient access to a racemic cyclohexene. This cyclohexene can be obtained via the sequence Diels-Alder/[3,3] sigmatropic rearrangement reaction starting from substituted 1-thiocyanatobutadienes. An efficient synthesis of the enone, a stable precursor of 1-thiocyanatobutadienes, is reported. Enolisation of this enone was studied to find the optimal conditions to get the desired 1-thiocyanatobutadienes with good Z-selectivity.     

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.     

Intramolecular Cyclizations of Allenic Acylureas and -Amides

Allenic acids are found to add to dicyclohexylcarbodiimide affording, in the presence of Et₂NH, the 4H-1,3-oxazin-4-ones 5 via 4 . Under neutral conditions, they add to diaryl- or pyridyl(cyclohexyl)carbodiimides and triphenylketene imine to give the corresponding tricyclo[5.2.2.0^1,5]undeca-4,8,10-trien-3-ones 7 , 8 , 9 , and 12 . The allenic phenyl ester 13a dimerises, on heating in a [2+2] head-to-head fashion, to 14 but fails to undergo intramolecular Diels-Alder cyclization, to 15 .     

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.     

Practical Asymmetric Diels-Alder Additions to Camphor-10-sulfonic-Acid-Derived Acrylates. Preliminary Communication

Starting from (+)-camphor-10-sulfonic acid (1) the chiral crystalline alcohols 3 and 11 were prepared in two steps. Lewis-acid-mediated [4+2]-additions of their acrylates to 1,3-dienes were studied. Notably, the crystalline acrylate 4 underwent TiCl₂ (OiPr)₂-promoted Diels-Alder addition to cyclopentadiene giving after recrystallization efficiently the pure (2R)-adduct 5 .