Some Unusual Products from the Thermal Reaction of Azulenes with Dimethyl Acetylenedicarboxylate

The thermal reaction of azulene-1-carbaldehydes 5 and 6 with excess dimethyl acetylenedicarboxylate (ADM) in decalin leads mainly to the formation of (1 + 1) and (1 + 2) adducts arising from the addition of ADM at the seven-membered ring of the azulenes (cf. Schemes 2 and 4). The (1 + 2) adducts are formed in a homo-Diels-Alder reaction of ADM and isomeric tricyclic carbaldehydes which are derived from the primary tricyclic carbaldehydes by reversible [1s5s]-C shifts (cf. Schemes 3 and 5). The thus formed pentacyclic carbaldehydes seem to undergo deep-seated skeletal rearrangements (cf. Scheme 7) which result finally in the formation of the formyl-tetrahydrocyclopenta[bc]acenaphthylene-tetraesters 12 and 19 , respectively. In other cases, e.g., azulene-1-carbaldehydes 7 and 8 (cf. Scheme 8), the thermal reaction with excess ADM furnishes only the already known tetracycfic (1 + 2) adducts of type anti- 26 to ‘anti’- 29 . The thermal reaction of 1,3,4,8-tetramethylazulene ( 9 ) with excess ADM in decalin resulted in the formation of two (1 + 2) and one (1 + 3) adduct in low yields (cf. Scheme 9). The latter turned out to be the 2,6-bridged barrelene derivative 32 . There are structural evidences that 32 is formed by similar pathways as the formyl-tetrahydrocyclopenta[bc]acenaphthylene-tetraesters (cf. Schemes 7 and 11). [²H₃]Me-Labelling experiments are in agreement with the proposed mechanisms (cf. Scheme 13).     

Zur Photochemie von 1H- und 2H-Indazolen in saurer Lösung

On the Photochemistry of 1H- and 2H-Indazoles in Acidic Solution It is shown that 1H- and 2H-indazoles (cf. Scheme 2) on protonation (0, 1N H₂SO₄ in water or alcoholic solution) give analogous indazolium ions (see Fig. 1 and 2) which on irradiation undergo heterolytic cleavage of the N (1), N (2) bond whereby aromatic nitrenium ions in the singlet ground state are formed (cf. Scheme 13). If the para position of these nitrenium ions is not occupied by a substituent (e.g. a methyl group) they are readily trapped by nucleophiles present (e.g. water, alcohols, chloride ions) to yield the corresponding 5-substituted 2-amino-benzaldehydes or acetophenones (cf. Schemes 4–10). Photolysis of indazole ( 4 ) and 3-methyl-indazole ( 5 ) in 0,75N H₂SO₄ in alcoholic solutions gives in addition minor amounts of the corresponding 3-substituted 2-amino-benzaldehydes and acetophenones, respectively (cf. Schemes 6 and 8 and Table 2). Phenylnitrenium ions carrying a methyl group in the para position give in aqueous sulfuric acid mainly the reduction products, i.e. 2-amino-5-methyl-benzaldehydes (cf. Schemes 11 and 12 and Table 3). In methanolic sulfuric acid, in addition to the reduction products, 6-methoxy substituted benzaldehydes are found (cf. Schemes 11 and 12 and Table 3) which are presumably formed by an addition-elimination mechanism (cf. Scheme 18). It is assumed that precursors of the reduction products are the corresponding nitrenium ions in the triplet ground state. Singlet-triplet conversion of the nitrenium ions may become efficient when addition of nucleophiles to the singlet nitrenium ions is reversible (cf. Scheme 22) thus, enhancing the probability of conversion or when conjugation in the singlet nitrenium ions is disturbed by steric effects (cf. Scheme 20) thus, destabilizing the singlet state relative to the triplet state.     

Formation of Heptaleno[1,2-c]furans and Heptaleno[1,2-c]furanones

The dehydrogenation reaction of the heptalene-4,5-dimethanols 4a and 4d , which do not undergo the double-bond-shift (DBS) process at ambient temperature, with basic MnO₂ in CH₂Cl₂ at room temperature, leads to the formation of the corresponding heptaleno[1,2-c]furans 6a and 6d , respectively, as well as to the corresponding heptaleno[1,2-c]furan-3-ones 7a and 7d , respectively (cf. Scheme 2 and 8). The formation of both product types necessarily involves a DBS process (cf. Scheme 7). The dehydrogenation reaction of the DBS isomer of 4a , i.e., 5a , with MnO₂ in CH₂Cl₂ at room temperature results, in addition to 6a and 7a , in the formation of the heptaleno[1,2-c]-furan-1-one 8a and, in small amounts, of the heptalene-4,5-dicarbaldehyde 9a (cf. Scheme 3). The benzo[a]heptalene-6,7-dimethanol 4c with a fixed position of the C?C bonds of the heptalene skeleton, on dehydrogenation with MnO₂ in CH₂Cl₂, gives only the corresponding furanone 11b (Scheme 4). By [²H₂]-labelling of the methanol function at C(7), it could be shown that the furanone formation takes place at the stage of the corresponding lactol [3-²H₂]- 15b (cf. Scheme 6). Heptalene-1,2-dimethanols 4c and 4e , which are, at room temperature, in thermal equilibrium with their corresponding DBS forms 5c and 5e , respectively, are dehydrogenated by MnO₂ in CH₂Cl₂ to give the corresponding heptaleno[1,2-c]furans 6c and 6e as well as the heptaleno[1,2-c]furan-3-ones 7c and 7e and, again, in small amounts, the heptaleno[1,2-c]furan-1-ones 8c and 8e , respectively (cf. Scheme 8). Therefore, it seems that the heptalene-1,2-dimethanols are responsible for the formation of the furan-1-ones (cf. Scheme 7). The methylenation of the furan-3-ones 7a and 7e with Tebbe's reagent leads to the formation of the 3-methyl-substituted heptaleno[1,2-c]furans 23a and 23e , respectively (cf. Scheme 9). The heptaleno[1,2-c]furans 6a, 6d , and 23a can be resolved into their antipodes on a Chiralcel OD column. The (P)-configuration is assigned to the heptaleno[1,2-c]furans showing a negative Cotton effect at ca. 320 nm in the CD spectrum in hexane (cf. Figs. 3–5 as well as Table 7). The (P)-configuration of (–)- 6a is correlated with the established (P)-configuration of the dimethanol (–)- 5a via dehydrogenation with MnO₂. The degree of twisting of the heptalene skeleton of 6 and 23 is determined by the Me-substitution pattern (cf. Table 9). The larger the heptalene gauche torsion angles are, the more hypsochromically shifted is the heptalene absorption band above 300 nm (cf. Table 7 and 8, as well as Figs. 6–9).     

A ‘One-Pot’ Anellation Method for the Transformation of Heptalene-4,5-dicarboxylates into Benzo[a]heptalenes

It has been found that dimethyl heptalene-4,5-dicarboxylates, when treated with 4 mol-equiv. of lithiated N,N-dialkylamino methyl sulfones or methyl phenyl sulfone, followed by 4 mol-equiv. of BuLi in THF in the temperature range of ?78 to 20°, give rise to the formation of 3-[(N,N-dialkylamino)sulfonyl]- or 3-(phenylsul-fonyl)benzo[a]heptalene-2,4-diols of. (cf. Scheme 4, and Tables 2 and 3). Accompanying products are 2,4-bis{[(N,N-dialkylamino)sulfonyl]methyl}- or 2,4-bis[(phenylsulfonyl)methyl]-4,10a-dihydro-3H-heptaleno[1,10-bc]furan-3-carboxylates as mixtures of diastereoisomers of. cf. Scheme 4, and (Tables 2 and 3) which are the result of a Michael addition reaction of the lithiated methyl sulfones at C(3) of the heptalene-4,5-dicarboxylates, followed by (sulfonyl)methylation of the methoxycarbonyl group at C(5) and cyclization of. (cf. Scheme 5). It is assumed that the benzo[a]heptalene formation is due to (sulfonyl)methylation of both methoxycarbonyl groups of the heptalene-4,5-dicarboxylates of. (cf. Schemes 6 and 8). The resulting bis-enolates 35 are deprotonated further. The thus formed tris-anions 36 can then cyclize to corresponding tris-anions 37 of cyclopenta[d]heptalenes which, after loss of N,N-dialkylamido sulfite or phenyl sulfinate, undergo a ring-enlargement reaction by 1,2-C migration finally leading to the observed benzo[a]heptalenes of. (cf. Schemes 8 and 9). The structures of the new product types have been finally established by X-ray crystal-structure analyses (cf. Figs. 1 and 2 as well as Exper. Part).     

Reactions of Thioketones with Dichlorocarbene

The reactions of sterically crowded cycloalkanethiones of type 2 with CHCl₃/NaOH under phase-transfer catalysis (PTC) with benzyl(triethyl)ammonium chloride (TEBA) as catalyst afforded the corresponding `gem.-dichlorothiiranes' of type 3 in good yields (cf. Scheme 2 and Table). The desulfurization, which, in some cases, occurred spontaneously, led to (dichloromethylidene)cycloalkanes of type 4 . Similar results were obtained using Seyferth's reagent in boiling benzene. In the case of 2,2,6,6-tetramethylcyclohexanethione, reaction under PTC conditions after 3 h yielded only the corresponding dichloromethylidene derivative; on the other hand, workup after 1 h gave (2,2,6,6-tetramethylcyclohexylidene)methanethione (thioketene 9 ; Scheme 5).     

Zur Photochemie von 2, 1-Benzisoxazolen (Anthranilen) und thermischen und photochemischen Umsetzungen von 2-Azido-acylbenzolen in stark saurer Lösung

On the Photochemistry of 2, 1-Benzisoxazoles (Anthraniles) and on the Thermal and Photochemical Decomposition of 2-Azido-acylbenzenes in Strongly Acidic Solution Anthranils 6 (Scheme 3), when irradiated with a mercury high-pressure lamp, in 96% sulfuric acid yielded, after work-up, 2-amino-5-hydroxy-acylbenzenes 8 and as side products 2-amino-3-hydroxy-acylbenzenes 9 (cf. Schemes 5–7 and Table 1). When C(5) of the anthranils 6 carries a methyl group a more complex reaction mixture is found after irradiation in 96% sulfuric acid (cf. Schemes 8 and 9): 3, 5-dimethyl-anthranil ( 6d ) yielded (after irradiation and acetylation) 2-acetyl- amino-5-methyl-acetophenone ( 15 ), 2-acetylamino-5-acetoxymethyl-acetophenone ( 18d ) and 2-acetylamino-5-acetoxy-6-methyl-acetophenone ( 12c ). The latter product was also formed after irradiation of 3, 4-dimethylanthranil ( 6c ) in 96% sulfuric acid. 3, 5, 7-Trimethyl-anthranil ( 6f ) formed under the same conditions 2-acetylamino-3, 5-dimethyl-acetophenone ( 15f ) and 2-acetylamino-5-acetoxymethyl-3-methyl-acetophenone ( 18f ). Since qualitatively the same product patterns were observed when the corresponding 2-azido-acetophenones 7 were decomposed in 96% sulfuric acid it is concluded that anthranilium ions (cf. 6b -H⊕, Scheme 11) on irradiation are transformed by cleavage of the N, O-bond into 2-acyl-phenylnitrenium ions (cf. 25b -H⊕) in the singlet ground state. The nitrenium ions are trapped directly by nucleophiles ( HSO ?₄ in 96% sulfuric acid), thus, yielding the hydroxy-acetophenones 8 and 9 (Scheme 11). If C(5) is blocked by a methyl group a [1, 2]-rearrangement of the methyl group may occur (cf. Scheme 13) or loss of sulfuric acid can lead to quinomethane iminium ions (cf. 32-H⊕ , Scheme 13) which will react with HSO ?₄ ions to yield, after hydrolysis and acetylation, the 5-acetoxymethyl substituted acetophenones 18d and 18f . It is assumed that the reduction products (2-acetylamino-acetophenones 15 ) are formed from the corresponding nitrenium ions in the triplet ground state.     

New Anellation Methods for the Synthesis of 8H-Heptaleno[1,10-bc]furans,-pyrroles,and -thiophenes

Heptaleno[1,2-c]furan-6-carbaldehydes such as 8 or their thiocarbaldehyde or iminomethyl derivatives easily undergo thermal cyclization, followed by a [1,5]- H shift, to give the corresponding heptalenodifurans, thienoheptalenofurans, as well as furoheptalenopyrroles (cf. Schemes 2 and 3). Generation of the 6-acetyl derivative of 8 from the corresponding secondary alcohol 15 with 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide (IBX) at 0° (cf. Scheme 4) leads directly to the formation of the cyclization product 16 which, upon standing at room temperature, undergoes the [1,5]-sigmatropic H-shift to the final difuran 17 . 1-Formylheptalene-4,5-dicarboxylates such as 9 can also be cyclized thermally, followed by the [1,5]-H shift, to the corresponding 8H-heptaleno[1,10-bc]furan-5,6-dicarboxylate 11 . On thiation with Lawesson′s reagent, 9 yields directly the corresponding heptalenothiophene 13 (cf. Scheme 3).     

Photosolvolysis of 2-Allylated Anilines to 2-Indanols

It is shown that 2-allylated anilines (cf. Schemes 2–4, 7, and 8) on irradiation in protic solvents such as H₂O. MeOH, and EtOH in the presence of H₂SO₄ undergo a novel photosolvolysis reaction to yield specifically trans-2-hydroxy- and trans-2-alkoxy-1-methylindanes. Intermediates are presumably tricyclo[4.3.0.0^1,8]nona-2,4-dienes formed in an intramolecular [2s + 2s] cycloaddition reaction (cf. Scheme 7). On the other hand, N,N,N-trimethyl-2-(1′-methylallyl)anilinium salts 18 (Scheme 6) and 2-(3′-butenyl)-N,N-dimethylaniline ( 17 ) lose on irradiation in MeOH or H₂SO₄/MeOH the ammonium group reductively to yield (1-methylallyl)benzene ( 19 ) and 1-methylindane ( 20 ), respectively.     

Bestrahlung von 4-allylierten 2,6-Dimethylanilinen in Methanol

Irradiation of 4-Allylated 2,6-Dimethylanilines in Methanol 4-Allyl-, 4-(1′-methylallyl)-, 4-(2′-butenyl)-, and 4-(1′,1′-dimethylallyl)-2,6-dimethylaniline ( 14–17 ; cf. Scheme 3) were obtained by the acid catalysed, thermal rearrangement of the corresponding N-allylated anilines in good yields. Aniline 14 , when irradiated with a high pressure mercury lamp through quartz in methanol, yielded as main product 4-(2′-methoxypropyl)-2,6-dimethylaniline ( 22 ; cf. Scheme 4) and, in addition, 2,6-dimethyl-4-propylaniline ( 18 ) and 4-cyclopropyl-2,6-dimethylaniline ( 23 ). The analogous products, namely erythro- and threo-4-(2′-methoxy-1′-methylpropyl)-2,6-dimethylaniline (erythro- and threo- 24 ), 2,6-dimethyl-4-(1′-methylpropyl)aniline ( 19 ), trans- and cis-2,6-dimethyl-4-(2′-methylcyclopropyl)aniline (trans- and cis- 25 ), as well as small amounts of 4-ethyl-2,6-dimethylaniline ( 26 ), were formed by irradiation of 15 in methanol (cf. Scheme 5). When this photoreaction was carried out in O-deuteriomethanol, erythro- and threo- 24 showed an up-take of one deuterium atom in the side chain. The mass spectra of erythro- and threo- 24 revealed that in 50% of the molecules the deuterium was located at the methyl group at C(1′) and in the other 50% at the methyl group at C(2′) (cf. Scheme 6). This is a good indication that the methanol addition products arise from methanolysis of intermediate spiro[2.5]octa-4,7-dien-6-imines (cf. Scheme 7). This assumption is further supported by the photoreaction of 17 in methanol (cf. Scheme 8) which led to the formation of 4-(2′-methoxy-1′,2′-dimethylpropyl)-2,6-dimethylaniline ( 28 ) as main product. The occurrence of a rearranged side chain in 28 can again be explained by the intervention of a spirodienimine 31 (cf. Scheme 9). In comparison with 14, 15 and 17 , the 2′-butenylaniline 16 reacted only sluggishly on irradiation in methanol (cf. Scheme 10). It is suggested that all photoproducts - except for the cyclopropyl derivatives which are formed presumably via a triplet di-π-methane rearrangement - arise from an intramolecular singlet electron-donor-acceptor complex between the aniline and ethylene chromophor of the side chain. Protonation of this complex at C(3′) or C(2′) will lead to diradicals (e.g. 33 and 34 , respectively, in Scheme 11). The diradicals of type 33 undergo ring closure to the corresponding spirodienimine intermediates (e.g. 31 ) whereas the diradicals of type 34 take up two hydrogen atoms to yield the photo-hydrogenated compounds (e.g. 21 ) or undergo to a minor extent fragmentation to side chain degraded products (e.g. 30 ; see also footnote 7).–Irradiation of 4-ally-2,6-dimethylaniline ( 14 ) in benzene or cyclohexane yielded the corresponding azo compound 38 (cf. Scheme 12), whereas its N,N-dimethyl derivative 41 was transformed into the cyclopropyl derivative 42 . The allyl moiety in 14 is not necessary for the formation of azo compounds since 2,4,6-trimethylaniline ( 39 ) exhibited the same type of photoreaction in benzene solution.     

New Results in the Synthesis of Styrylazulene Derivatives: Application of the ‘Anil synthesis’ to the preparation of azulenes substituted with styryl groups at the seven-membered ring

The synthesis of 4,6,8-trimethyl-1-[(E)-4-R-styryl]azulenes 5 (R=H, MeO, Cl) has been performed by Wittig reaction of 4,6,8-trimethylazulene-1-carbaldehyde ( 1 ) and the corresponding 4-(R-benzyl)(triphenyl)phosphonium chlorides 4 in the presence of EtONa/EtOH in boiling toluene (see Table 1). In the same way, guaiazulene-3-carbaldehyde ( 2 ) as well as dihydrolactaroviolin ( 3 ) yielded with 4a the corresponding styrylazulenes 6 and 7 , respectively (see Table 1). It has been found that 1 and 4b yield, in competition to the Wittig reaction, alkylation products, namely 8 and 9 , respectively (cf. Scheme 1). The reaction of 4,6,8-trimethylazulene ( 10 ) with 4b in toluene showed that azulenes can, indeed, be easily alkylated with the phosphonium salt 4b . 4,6,8-Trimethylazulene-2-carbaldehyde ( 12 ) has been synthesized from the corresponding carboxylate 15 by a reduction (LiAlH₄) and dehydrogenation (MnO₂) sequence (see Scheme 2). The Swern oxidation of the intermediate 2-(hydroxymethyl)azulene 16 yielded only 1,3-dichloroazulene derivatives (cf. Scheme 2). The Wittig reaction of 12 with 4a and 4b in the presence of EtONa/EtOH in toluene yielded the expected 2-styryl derivatives 19a and 19b , respectively (see Scheme 3). Again, the yield of 19b was reduced by a competing alkylation reaction of 19b with 4b which led to the formation of the 1-benzylated product 20 (see Scheme 3). The ‘anil synthesis’ of guaiazulene ( 21 ) and the 4-R-benzanils 22 (R=H, MeO, Cl, Me₂N) proceeded smoothyl under standard conditions (powered KOH in DMF) to yield the corresponding 4-[(E)-styryl]azulene derivatives 23 (see Table 4). In minor amounts, bis(azulen-4-yl) compounds of type 24 and 25 were also formed (see Table 4). The ‘anil reaction’ of 21 and 4-NO₂C₆H₄CH=NC₆H₅ ( 22e ) in DMF yielded no corresponding styrylazulene derivative 23e . Instead, (E)-1,2-bis(7-isopropyl-1-methylazulen-4-yl)ethene ( 27 ) was formed (see Scheme 4). The reaction of 4,6,8-trimethylazulene ( 10 ) and benzanil ( 22a ) in the presence of KOH in DMF yielded the benzanil adducts 28 to 31 (cf. Scheme 5). Their direct base-catalyzed transformation into the corresponding styryl-substituted azulenes could not be realized (cf. Scheme 6). However, the transformation succeeded smoothly with KOH in boiling EtOH after N-methylation (cf. Scheme 6).     

A New Alkylation Method for Heptalene‐4,5‐dicarboxylates and of One of Their Pseudoester Forms

Dimethyl heptalene‐4,5‐dicarboxylates

1 The locants of heptalene itself are maintained throughout the whole work. See footnote 4 in [1] for reasoning.

undergo preferentially a Michael addition reaction at C(3) with α‐lithiated alkyl phenyl sulfones at temperatures below ?50°, leading to corresponding cis‐configured 3,4‐dihydroheptalene‐4,5‐dicarboxylates (cf. Table 1, Schemes 3 and 4). The corresponding heptalenofuran‐1‐one‐type pseudoesters of dimethyl heptalene‐4,5‐dicarboxylates (Scheme 5) react with [(phenylsulfonyl)methyl]lithium almost exclusively at C(1) of the furanone group (Scheme 6). In contrast to this expected behavior, the uptake of 1‐[phenylsulfonyl)ethyl]lithium occurs at C(5) of the heptalenofuran‐1‐ones as long as they carry a Me group at C(11) (Schemes 6 and 7). The 1,4‐ as well as the 1,6‐addition products eliminate, on treatment with MeONa/MeOH in THF, benzenesulfinate, thus leading to 3‐ and 4‐alkylated dimethyl heptalene‐4,5‐dicarboxylates, respectively (Schemes 8–13). The configuration of the addition reaction of the nucleophiles to the inherently chiral heptalenes is discussed in detail (cf. Schemes 14–19) on the basis of a number of X‐ray crystal‐structure determinations as well as by studies of the temperature‐dependence of the ¹H‐NMR spectra of the addition products.     

Unexpected Products from the Reaction of 2,2,4,4- Tetramethylcyclobutane-1,3-dione with the Ma˛kosza Reagent

Reaction of 2,2,4,4-tetramethylcyclobutane-1,3-dione ( 2 ) under phase-transfer-catalysis (PTC) conditions (CHCl₃/aqueous NaOH) yielded a complex mixture of unexpected products (Scheme 2). From the organic phase, three ring-enlarged products 7 – 9 with a cyclopentane-1,3-dione (cf. 7 and 9 ) or a cyclopentenone skeleton (cf. 8 ) were isolated in low yield. After acidification of the aqueous phase, the oily residue was treated with CH₂N₂, and methyl 3-oxopentanoate 12 and dimethyl 2-hydroxybutanedioate 13 were obtained in almost equal amounts. The structures of 8 and 9 were established by X-ray crystal-structure analysis (Fig.). Mechanisms for the formation of the products, initiated by nucleophilic attack of trichloromethanide ion and opening of the cyclobutane ring, are proposed in Schemes 3 and 4.     

Electrofugal Fragmentation of Alkylcobalamin Derivatives Using Cob(I)Alamin and Heptamethyl Cob (I)yrinate as Catalysts

The cob (I)alamin- ( 1(I) ) and the heptamethyl cob(I)ynnate- ( 2(I) ) catalyzed transformation of an epoxide to the corresponding saturated hydrocarbon 3→4→5 is examined (see Schemes 1 and 3–5). Under the reaction conditions, the epoxyalkyl acetate 3 is opened by the catalysts with formation of appropriate (b?-hydroxyalkyl)-corrinoid derivatives ( 13 , 14 , 17 , 18 , see Schemes 12 and 14). Triggered by a transfer of electrons to the Co-corrin-π system, the Co, C-bond of the intermediates is broken, generating the alkenyl acetate 4 (cf. Schemes 12 and 14) following an electrofugal fragmentation (cf. Schemes 2 and 12). The double bond of 4 is also attacked by the catalysts, leading to the corresponding alkylcorrinoids ( 15 , 19 , see Schemes 12 and 14) which in turn are reduced by electrons from metallic zinc, the electron source in the system, inducing a reductive cleavage of the Co, C-bond with production of the saturated monoacetate 5 (see Schemes 2, 5 and 12). In the cascade of steps involved, the transfer of electrons to the intermediate alkylcorrinoids ( 13–15 , 17–19 , see Schemes 12 and 14) is shown to be rate-limiting. Comparing the two catalytic species 1(I) and 2(I) , it is shown that the ribonucleotide loop protects intermediate alkylcobalamins to some extent from an attack by electrons. The protective function of the ribonucleotide side-chain is shown to be present in alkylcobalamins existing in the base-on form (cf. Chap. 4 and see Scheme 14).     

Reaction of Hydroxymethyl- and Alkyl-Substituted Azulenes with Manganese Dioxide

It is shown that the 2-(hydroxymethyl)-1-methylazulenes 6 are being oxidized by activated MnO₂ in CH₂Cl₂ at room temperature to the corresponding azulene-1,2-dicarbaldehydes 7 (Scheme 2). Extension of the MnO₂ oxidation reaction to 1-methyl- and/or 3-methyl-substituted azulenes led to the formation of the corresponding azulene-1-carbaldehydes in excellent yields (Scheme 3). The reaction of unsymmetrically substituted 1,3-dimethyl-azulenes (cf. 15 in Scheme 4) with MnO₂ shows only little chemoselectivity. However, the observed ratio of the formed constitutionally isometric azulene-1-carbaldehydes is in agreement with the size of the orbital coefficients in the HOMO of the azulenes. The reaction of guaiazulene ( 18 ) with MnO₂ in dioxane/H₂O at room temperature gave mainly the expected carbaldehyde 19 . However, it was accompanied by the azulene-diones 20 and 21 (Scheme 5). The precursor of the demethylated compound 20 is the carbaldehyde 19 . Similarly, the MnO₂ reaction of 7-isopropyl-4-methyalazulene ( 22 ) as well as of 4,6,8-trimethylazulene ( 24 ) led to the formation of a mixture of the corresponding azulene-1,5-diones and azulene-1,7-diones 20 / 23 and 25 / 26 , respectively, in decent yields (Schemes 6 and 7). No MnO₂ reaction was observed with 5,7-dimethylazulene.     

Synthese und thermisches Verhalten von 6,8-Dimethylentricyclo[3.2.1.02,7]oct-3-enen; [3s 3s]-sigmatropische Umlagerungen von 6-Allenyl- und 6-Propargly-1- Methylen-cyclohexa-2,4-dienen in aromatische Kohlenwasserstoffe als Beispiele für konzertierte Semibenzol → Benzol-Umlagerungen

The tricyclic dimethylene hydrocarbons 5 , 6 , 7 , 8 and d₂- 5 , (Scheme 2), which are prepared by Wittig-reaction from the corresponding ketones, are rearranged, by heating, to 4-aryl-but-1-yne derivatives via the unstable 6-allenyl-1-methylene-cyclohexa-2, 4-diene intermediates (e.g. Scheme 14). Using the deuterium-labelled compound d₂- 5 , it was shown that the allenyl moiety, formed by a retro-Diels-Alder reaction (cycloreversion) of the tricyclic dimethylene compound, migrates with complete inversion in the final o-semibenzene-benzene rearrangement (Schemes 11 and 14). Reaction of 6-propargyl-cyclohexa-2, 4-dien-1-ones with triphenylphosphonium methylide gives 6-propargyl-1-methylene-cyclohexa-2 4-dienes, which immediately undergo a [3s, 3s]-rearrangement to form 4-aryl-buta-1, 2-dienes (Scheme 9). In contrast, the rearrangement of the corresponding 4-propargyl-1-methylene-cyclohexa-2, 5- dienes proceeds by a radical mechanism (Schemes 10 and 13).     

Synthesis and Reactions of a New Cyclobutanethione Derivative

The 3,3‐dichloro‐2,2,4,4‐tetramethylcyclobutanethione ( 4b ) was prepared from the parent diketone by successive reaction with PCl₅ and Lawesson reagent in pyridine. This new thioketone 4b was transformed into 1‐chlorocyclobutanesulfanyl chloride 5 and chloro 1‐chlorocyclobutyl disulfide 9 by treatment with PCl₅ and SCl₂, respectively, in chlorinated solvents (Schemes 1 and 2). These products reacted with S‐ and P‐nucleophiles by substitution of Cl⁻ at the S‐atom; e.g., the reaction with 4b yielded the di‐ and trisulfides 6b and 11 , respectively. Surprisingly, only pentasulfide 12 was formed in the reaction of 9 with thiobenzophenone (Scheme 3). In contrast to 5 and 9 , the corresponding chloro 1‐chlorocyclobutyl trisulfide 13 could not be detected, but reacted immediately with the starting thioketone 4b to give the tetrasulfide 14 (Scheme 4). Oxidation of 4b with 3‐chloroperbenzoic acid (mCPBA) yielded the corresponding thione oxides (= sulfine) 15 , which underwent 1,3‐dipolar cycloadditions with thioketones 3a and 4b (Scheme 5). Furthermore, 4b was shown to be a good dipolarophile in reactions with thiocarbonylium methanides (Scheme 6) and iminium ylides (= azomethine ylides; Scheme 7). In the case of phenyl azide, the reaction with 4b gave the symmetrical trithiolane 25 (Scheme 8).     

Chiral Acylsilanes in Organic Synthesis. Diastereoselective 1,2-Additions to Racemic Alkoxymethyl-Substituted Acylsilanes

The synthesis of the three alkoxymethyl-substituted acyisilanes 1 – 3 is described (Schemes 1 and 2). Their reactions with NaBH₄ as well as PhLi gave the corresponding alcohols with moderate to good diastereoisomeric induction (up to 78% de; see Table), depending upon the solvent used (Scheme 3). The results indicate that in Et₂O, the reactions with PhLi proceed via 6-membered chelates (see C in Scheme 4) leading to the products with high de's (74–78%). In THF, these chelates are not formed, and as a consequence, the additions take place with reversed and lower stereoselectivities (34–50% de).     

Unexpected Thermal Transformation of Aryl 3‐Arylprop‐2‐ynoates: Formation of 3‐(Diarylmethylidene)‐2,3‐dihydrofuran‐2‐ones

A number of aryl 3‐arylprop‐2‐ynoates 3 has been prepared (cf. Table 1 and Schemes 3 – 5). In contrast to aryl prop‐2‐ynoates and but‐2‐ynoates, 3‐arylprop‐2‐ynoates 3 (with the exception of 3b ) do not undergo, by flash vacuum pyrolysis (FVP), rearrangement to corresponding cyclohepta[b]furan‐2(2H)‐ones 2 (cf. Schemes 1 and 2). On melting, however, or in solution at temperatures >150°, the compounds 3 are converted stereospecifically to the dimers 3‐[(Z)‐diarylmethylidene]‐2,3‐dihydrofuran‐2‐ones (Z)‐ 11 and the cyclic anhydrides 12 of 1,4‐diarylnaphthalene‐2,3‐dicarboxylic acids, which also represent dimers of 3 , formed by loss of one molecule of the corresponding phenol from the aryloxy part (cf. Scheme 6). Small amounts of diaryl naphthalene‐2,3‐dicarboxylates 13 accompanied the product types (Z)‐ 11 and 12 , when the thermal transformation of 3 was performed in the molten state or at high concentration of 3 in solution (cf. Tables 2 and 4). The structure of the dihydrofuranone (Z)‐ 11c was established by an X‐ray crystal‐structure analysis (Fig. 1). The structures of the dihydrofuranones 11 and the cyclic anhydrides 12 indicate that the 3‐arylprop‐2‐ynoates 3 , on heating, must undergo an aryl O→C(3) migration leading to a reactive intermediate, which attacks a second molecule of 3 , finally under formation of (Z)‐ 11 or 12 . Formation of the diaryl dicarboxylates 13 , on the other hand, are the result of the well‐known thermal Diels‐Alder‐type dimerization of 3 without rearrangement (cf. Scheme 7). At low concentration of 3 in decalin, the decrease of 3 follows up to ca. 20% conversion first‐order kinetics (cf. Table 5), which is in agreement with a monomolecular rearrangement of 3 . Moreover, heating the highly reactive 2,4,6‐trimethylphenyl 3‐(4‐nitrophenyl)prop‐2‐ynonate ( 3f ) in the presence of a twofold molar amount of the much less reactive phenyl 3‐(4‐nitrophenyl)prop‐2‐ynonate ( 3g ) led, beside (Z)‐ 11f , to the cross products (Z)‐ 11fg , and, due to subsequent thermal isomerization, (E)‐ 11fg (cf. Scheme 10), the structures of which indicated that they were composed, as expected, of rearranged 3f and structurally unaltered 3g . Finally, thermal transposition of [¹⁷O]‐ 3i with the ¹⁷O‐label at the aryloxy group gave (Z)‐ and (E)‐[¹⁷O₂]‐ 11i with the ¹⁷O‐label of rearranged [¹⁷O]‐ 3i specifically at the oxo group of the two isomeric dihydrofuranones (cf. Scheme 8), indicating a highly ordered cyclic transition state of the aryl O→C(3) migration (cf. Scheme 9).     

Acid-Catalyzed [3,3]-Sigmatropic Rearrangements of N-Propargylanilines

The acid-catalyzed rearrangement of N-(1′,1′-dimethylprop-2′-ynyl)-, N-(1′-methylprop-2′-ynyl)-, and N-(1′-arylprop-2′-ynyl)-2,6-, 2,4,6-, 2,3,5,6-, and 2,3,4,5,6-substituted anilines in mixtures of 1N aqueous H₂SO₄ and ROH such as EtOH, PrOH, BuOH etc., or in CDCl₃ or CCl₄ in the presence of 4 to 9 mol-equiv. trifluoroacetic acid (TFA)has been investigated (cf. Scheme 12-25 and Tables 6 and 7). The rearrangement of N-(3′-X-1′,1′-dimethyl-prop-2′-ynyl)-2,6- and 2,4,6-trimethylanilines (X = Cl, Br, I) in CDCl₃/TFA occurs already at 20° with τ_1/2 of ca. 1 to 5 h to yield the corresponding 6-(1-X-3′-methylbuta-1,2′-dienyl)-2,6-dimethyl- or 2,4,6-trimethylcyclohexa-2,4-dien-1-iminium ions (cf. Scheme 13 and Footnotes 26 and 34) When the 4 position is not substituted, a consecutive [3,3]-sigmatropic rearrangement takes place to yield 2,6-dimethyl-4-(3′-X-1′,1′-dimethylprop-2′-ynyl)anilines (cf. Footnotes 26 and 34). A comparable behavior is exhibited by N-(3′-chloro-1′-phenylprop-2′-ynyl)-2,6-dimethylaniline ( 45 ., cf. Table 7). The acid-catalyzed rearrangement of the anilines with a Cl substituent at C(3′) in 1N aqueous H₂SO₄/ROH at 85-95°, in addition, leads to the formation of 7-chlorotricyclo[3.2.1.0^2,7]oct-3-en-8-ones as the result of an intramolecular Diels-Alder reaction of the primarily formed iminium ions followed by hydrolysis of the iminium function (or vice versa; cf. Schemes 13,23, and 25 as well as Table 7). When there is no X substituent at C(1′) of the iminium-ion intermediate, a [1,2]-sigmatropic shift of the allenyl moiety at C(6) occurs in competition to the [3,3]-sigmatropic rearrangement to yield the corresponding 3-allenyl-substituted anilines (cf. Schemes 12,14–18, and 20 as well as Tables 6 and 7). The rearrangement of (?)?(S)-N-(1′-phenylprop-2′-ynyl)-2,6-dimethylaniline ((?)- 38 ; cf. Table 7) in a mixture of 1N H₂SO₄/PrOH at 86° leads to the formation of (?)-(R)-3-(3′-phenylpropa-1′,2′-dienyl)-2,6-dimethylaniline ((?)- 91 ), (+)-(E)- and (?)-(Z)-6-benzylidene-1,5-dimethyltricyclo[3.2.1.0^2′7]oct-3-en-8-one ((+)-(E)- and (?)-(Z)- 92 , respectively), and (?)-(S)-2,6-dimethyl-4-( 1′-phenylprop-2′-ynyl)aniline((?)- 93 ). Recovered starting material (10%) showed a loss of 18% of its original optical purity. On the other hand, (+)-(E)- and (?)-(Z)- 92 showed the same optical purity as (minus;)- 38 , as expected for intramolecular concerted processes. The CD of (+)-(E)- and (?)-(Z)- 92 clearly showed that their tricyclic skeletons possess enantiomorphic structures (cf. Fig. 1). Similar results were obtained from the acid-catalyzed rearrangement of (?)-(S)-N-(3′-chloro-1′phenylprop-2′-ynyl)-2,6-dimethylaniline ((?)- 45 ; cf. Table 7). The recovered starting material exhibited in this case a loss of 48% of its original optical purity, showing that the Cl substituent favors the heterolytic cleavage of the N–C(1′) bond in (?)- 45. A still higher degree (78%) of loss of optical activity of the starting aniline was observed in the acid-catalyzed rearrangement of (?)-(S)-2,6-dimethyl-N-[1′-(p-tolyl)prop-2′-ynyl]aniline ((?)- 42 ; cf. Scheme 25). N-[1′-(p-anisyl)prop-2-ynyl]-2,4,6-trimethylaniline( 43 ; cf. Scheme 25) underwent no acid-catalyzed [3,3]-sigmatropic rearrangement at all. The acid-catalyzed rearrangement of N-(1′,1′-dimethylprop-2′-ynyl)aniline ( 25 ; cf. Scheme 10) in 1N H₂SO₄/BuOH at 100° led to no product formation due to the sensitivity of the expected product 53 against the reaction conditions. On the other hand, the acid-catalyzed rearrangement of the corresponding 3′-Cl derivative at 130° in aqueous H₂SO₄ in ethylene glycol led to the formation of 1,2,3,4-tetrahydro-2,2-dimethylquinolin-4-on ( 54 ; cf. Scheme 10), the hydrolysis product of the expected 4-chloro-1,2-dihydro-2,2-dimethylquinoline ( 56 ). Similarly, the acid-catalyzed rearrangement of N-(3′-bromo-1′-methylprop-2′-ynyl)-2,6-diisopropylaniline ( 37 ; cf. Scheme 21) yielded, by loss of one i-Pr group, 1,2,3,4-tetrahydro-8-isopropyl-2-methylquinolin-4-one ( 59 ).     

Tetramethylheptalenes and Their Tricarbonylchromium Complexes: Synthesis,Structures, and Thermal Rearrangements

The thermal 4 : 1 equilibrium mixture of 1,3,5,6- and 1,3,5,10-tetramethylheptalene ( 13a and 13b , resp.) has been prepared, starting from the thermal equilibrium mixture of dimethyl 6,8,10-trimethylheptalene-1,2- and -4,5-dicarboxylate ( 6a and 6b , resp.; cf. Scheme 5). These heptalenes undergo double-bond shifts (DBS) even at ambient temperature. Treatment of the mixture 13a / 13b 4 : 1 with [Cr(CO)₃(NH₃)₃] in boiling 1,2-dimethoxyethane resulted in the formation of all four possible mononuclear Cr(CO)₃ complexes 19a – 19d of 13a and 13b , as well as two binuclear Cr(CO)₃ complexes 20a and 20b , respectively, in a total yield of 87% (cf. Scheme 7). The mixture of complexes was separated by column chromatography, followed by preparative HPLC (cf. Fig. 2). The structures of all complexes were established by X-ray crystal-structure analyses (complex 19b and 20b ; cf. Figs. 6 – 8) and extensive ¹H-NMR measurements (cf. Table 3). In 20b , the two Cr(CO)₃ groups are linked in a `syn'-mode to the highly twisted heptalene π-skeleton. The correspondence of the <sup>1</sup>H-NMR data of 20a with that of 20b indicates that the two Cr(CO)<sub>3</sub> groups in 20a also have a `syn'-arrangement. The thermal behavior of the mononuclear complexes 19a – 19d has been studied at 85° in hexafluorobenzene (HFB). At this temperature, all four complexes undergo rearrangement to the same thermal equilibrium mixture (cf. Table 8). The rates for the thermal equilibration of each complex have been determined by ¹H-NMR measurements (cf. Figs. 9 – 12) and analyzed by seven different kinetic schemes (Chapt. 2). The equilibration rates are in agreement with two different haptotropic rearrangements that take place, namely intra- and inter-ring shifts of the Cr(CO)₃ group, whereby both rearrangements are accompanied by DBS of the heptalene π-skeleton (cf. Scheme 9). All individual kinetic steps possess similar ΔG^≠ values in the range of 29 – 31 kcal⋅mol⁻¹ (cf. Table 8). The occurrence of inter-ring haptotropic migrations of Cr(CO)₃ groups has already been established for anellated aromatic systems (cf. Scheme 10); however, it is the first time that these rearrangements have been unequivocally demonstrated for Cr(CO)₃ complexes of non-planar bicyclic [4n]annulenes, such as heptalenes. The mechanism of migration may be similar to that proposed for aromatic systems (cf. Schemes 10 and 11).