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).     

New Heptalenes Substituted with Extended π-Systems

The synthesis of π-substituted heptalenecarboxylates or -dicarboxylates, starting with the easily available dimethyl 9-isopropyl-1, 6-dimethylheptalene-4, 5-dicarboxylate ( 2b ), are described. Treatment of 2b with t-BuOK and C₂Cl₆ at ?78° leads to the chemoselective introduction of a Cl substituent in Me-C(1) (see 5b in Scheme 1). Formation of the corresponding triphenylphosphonium salt 7b via the iodide 6b (Scheme 2) allowed a Wittig reaction with cinnamaldehyde in the two-phase system CH₂Cl₂/2N NaOH. Transformation of the 4, 5-dicar-boxylate of 2b into the corresponding pseudo-ester 10b allowed the selective reduction of the carbonyl function at C(4) with DIBAH to yield the corresponding 4-carbaldehyde 11b (Scheme 3). Wittig reaction of 11b with (benzyl) triphenylphosphonium bromide led to the introduction of the 4-phenylbuta-1, 3-dienyl substituent at C(4). The combination of both Wittig reactions led to the synthesis of the 1, 4-bis(4-phenylbuta-1, 3-dienyl)-substituted heptalene-5-carboxylate (all-E)- 17b (Scheme 5). In a similar manner, by applying a Horner-Wadsworth-Emmons reaction, followed by the Wittig reaction, the donor-acceptor substituted heptalene-5-carboxylate (E;E)- 22b was synthesized (Scheme7). Most of these new heptalenes are in solution, at room temperature, in thermal equilibrium with their double-bond shifted (DBS) isomers. In the case of (all-E)- 17b and (E;E)- 22b , irradiation of the thermal equilibrium mixture with light of λ -(439 ± 10) nm led to a strong preponderance ( > 90%) of the DBS isomers 17a and (E;E)- 22a , respectively (Schemes 6 and 7). Heating of the photo-mixtures at 40° re-established quickly the thermal equilibrium mixtures. Heptalenes-carboxylates (all-E)- 17a and (E;E)- 22a which represent the off-state of a 1,4-conjugative switch (CS) system show typical heptalene UV/VIS spectra with a bathochromically shifted heptalene band III and comparably weak heptalene bands II and I which appear only as shoulders (Figs. 4 and 5). In contrast, the DBS isomers (all-E)- 17b and (all-E)- 22b , equivalent to the on-state of a 1,4-CS system, exhibit extremely intense heptalene bands I and, possibly, II which appear as a broad absorption band at 440 and 445 nm, respectively, thus indicating that the CSs (all-E)- 17a ?(all-E)- 17b and (E;E)- 22a ?(E;E)- 22b are perfectly working.     

New Syntheses of Di-π-Substituted Heptalenes

To study the effect of double-bond shifts (DBS) in different type of heptalenes linked to extended π-systems, several di-π-substituted heptalenes were synthesized. 6-[(E)-Styryl]heptalene-dicarboxylate 4 was smoothly converted to 1-(chloromethyl)heptalene-dicarboxylate 5 by treatment with t-BuOK and C₂Cl₆ in THF at −78°. The one-pot reaction of 5 and P(OEt)₃ in the presence of NaI, followed by Wittig-Horner reaction, afforded the 1,6-di-π-substituted heptalene 6 . The reaction of 6-[(1E,3E)-4-phenylbuta-1,3-dienyl]heptalenes 7 or 15 with t-BuOK and benzaldehyde in THF led to the formation of the 1,6-di-π-substituted heptalenes 13 or 16 , together with transesterification products 14 or 17 . The transformation of the MeOCO group at C(4) of 6-[(E)-styryl]heptalene-dicarboxylate 4 to a phenylbuta-1,3-dienyl substituent afforded the 4,6-di-π-substituted heptalene 21a , which is in thermal equilibrium with its DBS isomer 21b in solution. Oxidation of heptalene 22 with SeO₂ in dioxane gave carbaldehyde 23 , which was then subjected to a Wittig reaction to give the 6,9-di-π-substituted heptalene-dicarboxylate 24 .     

Thermal and Ru-catalyzed Reactions of Styryl-Substituted Azulenes with Dimethyl Acetylenedicarboxylate

The thermal reaction of 1-[(E)-styrl]azulenes with dimethyl acetylenedicarboxylate (ADM) in decalin at 190–200° does not lead to the formation fo the corresponding heptalene-1,2-dicarboxylates (Scheme 2). Main products are the corresponding azulene-1,2-dicarboxylates (see 4 and 9 ), accompanied by the benzanellated azulenes trans- 10a and trans- 11 , respectively. The latter compounds are formed by a Diels-Alder reaction of the starting azulenes and ADM, followed by an ene reaction with ADM (cf. Scheme 3). The [RuH₂(PPh₃)₄]-catalyzed reaction of 4,6,8-trimethyl-1-[(E)-4-R-styryl]azulenes (R=H, MeO, Cl; Scheme 4) with ADM in MeCN at 110° yields again the azulene-1,2-dicarboxylates as main products. However, in this case, the corresponding heptalene-1,2-dicarboxylates are also formed in small amounts (3–5%; Scheme 4). The benzanellated azulenes trans- 10a and trans- 10b are also found in small amounts (2–3%) in the reaction mixture. ADM Addition products at C(3) of the azulene ring as well as at C(2) of the styryl moiety are also observed in minor amounts (1–3%). Similar results are obtained in the [RuH₂(PPh₃)₄]-catalyzed reaction of 3-[(E)-styryl]guaiazulene ((E)- 8 ; Scheme 5) with ADM in MeCN. However, in this case, no heptalene formation is observed, and the amount of the ADM-addition products at C(2) of the styryl group is remarkably increased (29%). That the substitutent pattern at the seven-membered ring of (E)- 8 is not responsible for the failure of heptalene formation is demonstrated by the Ru-catalyzed reaction of 7-isopropyl-4-methyl-1-[(E)-styryl]azulene ((E)- 23 ; Scheme 11) with ADM in MeCN, yielding the corresponding heptalene-1,2-dicarboxylate (E)- 26 (10%). Again, the main product is the corresponding azulene-1,2-dicarboxylate 25 (20%). Reaction of 4,6,8-trimethyl-2-[(E)-styryl]azulene ((E)- 27 ; Scheme 12) and ADM yields the heptalene-dicarboxylates (E)- 30A / B , purely thermally in decalin (28%) as well as Ru-catalyzed in MeCN (40%). Whereas only small amounts of the azulene-1,2-dicarboxylate 8 (1 and 5%, respectively) are formed, the corresponding benzanellated azulene trans- 29 ist found to be the second main product (21 and 10%, respectively) under both reaction conditions. The thermal reaction yields also the benzanellated azulene 28 which is not found in the catalyzed variant of the reaction. Heptalene-1,2-dicarboxylates are also formed from 4-[(E)-styryl]azulenes (e.g. (E)- 33 and (E)- 34 ; Scheme 14) and ADM at 180–190° in decalin and at 110° in MeCN by [RuH₂(PPh₃)₄] catalysis. The yields (30%) are much better in the catalyzed reaction. The formation of by-products (e.g. 39–41 ; Scheme 14) in small amounts (0.5–5%) in the Ru-catalyzed reactions allows to understand better the reactivity of zwitterions (e.g. 42 ) and their triyclic follow-up products (e.g. 43 ) built from azulenes and ADM (cf. Scheme 15).     

Formation of Cyclic ‘ortho’-Anhydrides of Heptalene-1,2-dicarboxylic Acids

1-(Alkoixycarbonyl)heptalene-2-carboxylic acids as well as 2-(alkoxycarbonyl)heptalene-1-carboxylic acids react with the iminium salt formed from N,N-dimethylformamide (DMF) and oxalyl chloride, in the presence of an alcohol, to yield the corresponding cyclic ‘ortho’ -anhydrides (ψ-esters; cf. Schemes 2,3,6, and 8). When the alkoxy moiety of the acids and the alcohols is different, then diastereoisomeric ‘ortho’ -anhydrides are formed due to the non-planarity of the heptalene skeleton. The approach of the alcohol from the β-side is strongly favored (cf. Scheme 5 and Table 1). This effect can be attributed to the bent topology of the heptalene skeleton which sterically hinders the approach of the nucleophile from the α-side of the postulated intermediates, i.e. the charged O-alkylated anhydrides of type 19 (cf. Scheme 6). Whereas the ‘ortho’-anhydrides with four substituents in the ‘peri’ -positions of the heptalene skeleton are configurationally stable up to 100°, the ‘ortho’ -anhydrides with only three ‘peri’ -substituents slowly epimerize at 100° (cf. Scheme 7) due to the thermally induced inversion of the configuration of the heptalene skeleton.     

σ-Skeletal-Rearrangement of Heptalenes: Thermal Transformation of Heptalene-1,2-dicarboxylates into Heptalene-1,3-dicarboxylates

It is shown that dimethyl heptalene-1,2-dicarboxylates undergo rearrangements at temperatures > 200° to yield the corresponding 1,3-dicarboxylates, which are isolated as the more stable 3,5-dicarboxylates. ²H- and ¹³C-labelling experiments with dimethyl 7-isopropyl-5,10-dimethylheptalene-1,2-dicarboxylate ( 1 ) which is rearranged into dimethyl 9-isopropyl-1,6-dimethylheptalene-3,5-dicarboxylates. ( 2 ) indicate that the reaction occurs by interchange of C(2) and C(3) in the heptalene skeleton of 1 . Thus, the transformation of 1 into 2 represents the first thermal σ-skeletal rearrangement of heptalenes. The structures of 1 and 2 are discussed in terms of an X-ray analysis and the spectral data.     

Synthesis and Characterization of New Heptalenes with Extended π‐Systems Attached to Them

Methyl heptalenecarboxylates of type A and B with π(1) and π(2) substituents in 1,4‐relation (Scheme 1) were synthetized starting with dimethyl 1‐methylheptalene‐4,5‐dicarboxylates 5b and 6b derived from 7‐isopropyl‐1,4‐dimethylazulene (=guaiazulene) and 1,4,6,8‐tetramethylazulene by thermal reaction with dimethyl acetylenedicarboxylate. The further general way of proceeding for the introduction of the π(1) and π(2) substituents is displayed in Scheme 3, and the thus obtained methyl heptalene‐5‐carboxylates of type A and B are listed in Table 1. The C?C bonds of the 2‐arylethenyl and 4‐arylbuta‐1,3‐dien‐1‐yl groups of π(1) and π(2) were in all cases (E)‐configured and showed s‐trans conformation at the C? C bonds (X‐ray and ¹H‐NOE evidence) in the B ‐type as well as in the A ‐type heptalenes (cf. Figs. 5–12). All B ‐type heptalenes showed a strongly enhanced heptalene band I in the wavelength region 440–490 nm in hexane/CH₂Cl₂ 9 : 1 (cf. Table 4 and Figs. 13–20). The A ‐type heptalenes showed in this region only weak absorption, recognizable as shoulders or simply tailing of the dominating heptalene bands II/III (Table 5). Absorption band I of the B ‐type heptalenes appeared almost at the same wavelength as the longest wavelength absorption band of comparable open‐chain α,ω‐diarylpolyenes (cf. Fig. 21). The cyclic double bond shift (DBS) of the A ‐ and B ‐type heptalenes could be photochemically steered in one or the other direction by selective irradiation (cf. Fig. 22).     

Thermal Reaction of Azulene and Some of Its Symmetrically Substituted Methyl Derivatives with Dimethyl Acetylenedicarboxylate

It is shown that azulene ( 1 ) and dimethyl acetylenedicarboxylate (ADM) in a fourfold molar excess react at 200° in decalin to yield, beside the known heptalene- ( 5 ) and azulene-1,2-dicarboxylates ( 6 ), in an amount of 1.6% tetramethyl (1RS,2RS,5SR,8RS)-tetracyclo[6.2.2.2^2,50^1,5]tetradeca-3,6,9,11,13-pentaene-3,4,9,10-tetracarboxylate(‘anti’-7) as a result of a SHOMO (azulene)/LUMO(ADM)-controlled addition of ADM to the seven-membered ring of 1 followed by a Diels-Alder reaction of the so formed tricyclic intermediate 16 (cf. Scheme 3) with a second molecule of ADM. The structure of ‘anti’-7 was confirmed by an X-ray diffraction analysis. Similarly, the thermal reaction of 5,7-dimehtylazulene ( 3 ) with excess ADM in decalin at 120° led to the formation of ca. 1% of ‘anti’- 12 , the 7,12-dimethyl derivative of‘anti’-7, beside of the corresponding heptalene- 10 and azulene-1,2-dicaboxylated (cf Scheme 2). The introduction of Me groups at C(1)and C(3)of azulene ( 1 ) and its 5,7-dimethyl derivative 3 strongly enhance the thermal formation of the corresponding tetracyclic compound. Thus, 1,3-dimethylazulene ( 2 ) in the presence of a sevenfold molar excess of ADM at 200° yielded 20% of ‘anti’- 9 beside an equal amount of dimethyl 3-mehtylazulene-1,2-dicarboxylate ( 8 ;cf. Scheme 1), and 1,3,5,7-tetramethylazulene ( 4 ) with a fourfold molar excess of ADM AT 200° gave a yield of 37% of‘anti’- 15 beside small amount of the corresponding heptalene- 13 and azulene-1,2-dicarboxylates 14 (cf.Scheme 2).     

Light-Induced,Thermal, and Acid-Catalyzed π-Skeletal Rearrangements of Five-Ring-Annelated Heptalenes

It is shown that, upon irradiation in CDCl₃ solution, 5,6,8,10-tetramethylheptalene-1,2-dicarboxylic anhydride ( 6 ) rearranges to its double-bond-shift (DBS) isomer 7 in an equilibrium reaction (Scheme 2). The isomer 7 is DBS stable at ?50°. At ca. 30°, a thermal equilibrium with 97.8% of 6 and 2.2% of 7 is rapidly established. Similarly, the ‘ortho’-anhydrides 9 and 11 (Schemes 4 and 5) can be rearranged to their corresponding DBS isomers 12 and 13 , respectively. Whereas 12 is DBS stable at 30° (at 100° in tetralin, 94.0% of 9 are in equilibrium with 6.0% of 12 ), the i-Pr-substituted isomer 13 is already at 30° in thermal equilibrium with 11 leading to 98.7% of 11 and 1.3% of 13 . It is shown by rearrangement of diasteroisomeric ‘ortho’-anhydrides of known relative and absolute configuration (Scheme 6) that the DBS in such five-ring-annelated heptalenes occurs with retention of the configuration of the heptalene skeleton as already established for other heptalene compounds. It is found that the DBS process may also take place under acid catalysis (e.g. HCl/CH₃OH), thus yielding 9 from 12 (Scheme 9). The ‘ortho’-anhydrides 21 and 23 (Scheme 10) which are isomeric with 9 and 11 (Scheme 3) undergo rapid DBS' already at room temperature. The thermal equilibrium 21?22 consists of 18% of 21 and 82% of 22 at 30° and that of 23?24 of 17% of 23 and 83% of 24 at ?30°. From these equilibrium mixtures, the pure DBS isomer 22 can be obtained by crystallization. Again, these rapid DBS' occur with retention of configuration of the heptalene skeleton (Fig. 4).     

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).     

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.     

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.     

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).     

New Products from the Heptalene‐Forming Reaction of Azulenes and Acetylenedicarboxylates in Polar Media

A number of azulenes 1 , in particular those with π‐substituents at C(6) such as phenyl, 3,5‐dimethylphenyl, and 4‐biphenyl, have been reacted with 3 mol‐equiv. of dimethyl acetylenedicarboxylate (ADM) in MeCN at 110° (cf. Scheme 1). Main products had been, in all cases, the corresponding heptalene‐4,5‐dicarboxylates 2 . However, a whole number of side products, mainly rearranged (1+2)‐adducts with two molecules of ADM, in amounts of 0.2–9% were also isolated and characterized (cf. Scheme 2). The 2a,8a‐dihydro‐3,4‐ethenoazulene‐1,2‐dicarboxylates 14 , formed by energetically favorable ring closure from the solvent‐stabilized zwitterions 15 , resulting from bond heterolysis in the primary cycloadducts 12 (cf. Scheme 3), have been mechanistically identified as the pivotal intermediates responsible for the formation of all side product (cf. Schemes 5, 9, 12, and 13). Deuterium‐labeling experiments were in agreement with the proposed mechanisms, indicating that sigmatropic [1,5s]‐H shifts in 14 (cf. Scheme 6) as well as isoconjugate [1,4s]‐H shifts in resonance‐stabilized zwitterions of type 21 (cf. Scheme 9) are the crucial steps for side‐product formation. It is postulated that a concluding antarafacial 8e‐dyotropic rearrangement is responsible for the appearance of the 2,4a‐dihydrophenanthrene‐tetracarboxylates of type trans‐ 6 (cf. Scheme 9) in the reaction mixtures, which further rearrange thermally by a not fully understood mechanism into the isomeric tetracarboxylates 7 (cf. Schemes 10 and 11). Most surprising is the presence of a small amount (0.3–1%) of the azulene‐4,5,7,8‐tetracarboxylate 9 in the reaction mixture of azulene 1a and ADM. It is proposed that the formation of 9 is the result of a [1,5s]‐C shift in the spiro‐linked intermediates 24 , which, after prototropic shift and take‐up of a third molecule of ADM, disintegrate by a retro‐Diels‐Alder reaction into 9 and the phthalic diesters 30 (cf. Scheme 12). The UV/VIS spectra of the π‐substituted heptalene‐4,5‐dicarboxylates 2d – 2f and their double‐bond shifted (DBS) forms 2d – 2f (cf. Table 4 and Figs. 9–12) exhibit in comparison with the heptalene‐dicarboxylates 2a and 2′a , carrying a t‐Bu group at C(8), only marginal differences, which are mainly found in the relative intensity and position of heptalene bands II and III .     

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).     

Benzo[a]heptalenes from Heptaleno[1,2‐c]furans. Part I

It is shown that heptaleno[1,2‐c]furans 1 , which are available in two steps from heptalene‐4,5‐dicarboxylates by reduction and oxidative dehydrogenation of the corresponding vicinal dimethanols 2 with MnO₂ or IBX (Scheme 4), react thermally in a Diels–Alder‐type [4+2] cycloaddition at the furan ring with a number of electron‐deficient dipolarophiles to yield the corresponding 1,4‐epoxybenzo[d]heptalenes (cf. Schemes 6, 15, 17, and 19). The thermal reaction between dimethyl acetylenedicarboxylate (ADM) and 1 leads, kinetically controlled, via a sterically less‐congested transition state (Fig. 4) to the formation of the (M*)‐configured 1,4‐dihydro‐1,4‐epoxybenzo[a]heptalenes, which undergo a cyclic double‐bond shift to the energetically more‐relaxed benzo[d]heptalenes 4 (Schemes 6 and 7). Most of the latter ones exhibit under thermal conditions epimerization at the axis of chirality, so that the (M*)‐ and (P*)‐stereoisomers are found in reaction mixtures. The (P*)‐configured forms of 4 are favored in thermal equilibration experiments, in agreement with AM1 calculations (Table 1). The relative (P*,1S*,4R*)‐ and (M*,1S*,4R*)‐configuration of the crystalline main stereoisomers of the benzo[d]heptalene‐2,3‐dicarboxylates 4a and 4f , respectively, was unequivocally established by an X‐ray crystal‐structure determination (Figs. 1 and 2). Acid‐induced rearrangement of 4 led to the formation of the corresponding 4‐hydroxybenzo[a]heptalene‐2,3‐dicarboxylates 5 in moderate‐to‐good yields (Schemes 8, 13, and 14). When the aromatization reaction is performed in the presence of trifluoroacetic acid (TFA), trifluoroacetates of type 6 and 13 (Schemes 8, 12, and 13) are also formed via deprotonation of the intermediate tropylium ions of type 7 (Scheme 11). Thermal reaction of 1 with dimethyl maleate gave the 2,3‐exo‐ and 2,3‐endo‐configured dicarboxylates 14 as mixtures of their (P*)‐ and (M*)‐epimers (Scheme 15). Treatment of these forms with lithium di(isopropyl)amide (LDA) at ?70° gave the expected benzo[a]heptalene‐2,3‐dicarboxylates 15 in good yields (Scheme 16). Fumaronitrile reacted thermally also with 1 to the corresponding 2‐exo,3‐endo‐ and 2‐endo,3‐exo‐configured adducts 17 , again as mixtures of their (P*)‐ and (M*)‐epimers (Scheme 17), which smoothly rearranged on heating in dimethoxyethane (DME) in the presence of Cs₂CO₃ to the benzo[a]heptalene‐2,3‐dicarbonitriles 18 (Scheme 18). Some cursory experiments demonstrated that hex‐3‐yne‐2,5‐dione and (E)/(Z)‐hexa‐3‐ene‐2,5‐dione undergo also the Diels–Alder‐type cycloaddition reaction with 1 (Scheme 19). The mixtures of the stereoisomers of the 2,3‐diacetyl‐1,4‐epoxytetrahydrobenzo[d]heptalenes 22 gave, on treatment with Cs₂CO₃ in DME at 80°, only mixtures of the regioisomeric inner aldol products 24 and 25 of the intermediately formed benzo[a]heptalenes 23 (Scheme 20).     

From Blue Azulenes to Blue Heptalenes – New Strongly Polarized π‐Convertible Heptalenes

The 1,5,6,8,10‐pentamethylheptalene‐4‐carboxaldehyde ( 4b ) (together with its double‐bond‐shifted (DBS) isomer 4a ) and methyl 4‐formyl‐1,6,8,10‐tetramethylheptalene‐5‐carboxylate ( 15b ) were synthesized (Schemes 3 and 7, resp.). Aminoethenylation of 4a / 4b with N,N‐dimethylformamide dimethyl acetal (=1,1‐dimethoxy‐N,N‐dimethylmethanamine=DMFDMA) led in DMF to 1‐[(1E)‐2‐(dimethylamino)ethenyl]‐5,6,8,10‐tetramethylheptalene‐2‐carboxaldehyde ( 18a ; Scheme 9), whereas the stronger aminoethenylation agent N,N,N′,N′,N″,N″‐hexamethylmethanetriamine (=tris(dimethylamino)methane=TDMAM) gave an almost 1 : 1 mixture of 18a and 1‐[(1E)‐2‐(dimethylamino)ethenyl]‐5,6,8,10‐tetramethylheptalene‐4‐carboxaldehyde ( 20b ; Scheme 11). Carboxylate 15b delivered with DMFDMA on heating in DMF the expected aminoethenylation product 19b (Scheme 10). The aminoethenylated heptalenecarboxaldehydes were treated with malononitrile in CH₂Cl₂ in the presence of TiCl₄/pyridine to yield the corresponding malononitrile derivatives 23b, 24b , and 26a (Schemes 13 and 14). The photochemically induced DBS process of the heptalenecarboxaldehydes as ‘soft’ merocyanines and their malononitrile derivatives as ‘strong’ merocyanines of almost zwitterionic nature were studied in detail (Figs. 10–29) with the result that 1,4‐donor/acceptor substituted heptalenes are cleaner switchable than 1,2‐donor/acceptor‐substituted heptalenes.     

On the Formation of 2‐Sulfonylbenzo[a]heptalene‐1,3‐diols as Precursors for the Synthesis of Colchicinoids

The benzo[a]heptalene formation from 4‐[(R‐sulfonyl)acetyl]heptalene‐5‐carboxylates 15 and 5‐[(R‐sulfonyl)acetyl]heptalene‐4‐carboxylates 16 (R=Ph or morpholino) in the presence of R′SO₂CH₂Li and BuLi has been investigated (Scheme 6). Only the sulfonyl moiety linked to the C?O group at C(4) of the heptalene skeleton is found at C(3) of the formed benzo[a]heptalene‐2,4‐diols 3 in accordance with the general mechanism of their formation (Scheme 3). Intermediates that might rearrange to corresponding 2‐sulfonylbenzo[a]heptalene‐1,3‐diols lose HO^? under the reaction conditions to yield the corresponding cyclopenta[d]heptalenones of type 11 (Schemes 6 and 7). However, the presence of an additional Me group at C(α) of the lithioalkyl sulfones suppresses the loss of HO^?, and 4‐methyl‐2‐sulfonylbenzo[a]heptalene‐1,3‐diols of type 4c have been isolated and characterized for the first time (Schemes 8 and 10). A number of X‐ray crystal‐structure analyses of starting materials and of the new benzo[a]heptalenes have been performed. Finally, benzo[a]heptalene 4c has been transformed into its 1,2,3‐trimethoxy derivative 23 , a benzo[a]heptalene with the colchicinoid substitution pattern at ring A (Scheme 11).     

Synthesis and Properties of Novel (Tricarbonyl)(heptalene)chromium Complexes

A number of novel (tricarbonyl)chromium complexes of heptalenes 10 – 13, 16 – 20 and 23 – 25 have been prepared by reaction of the heptalenes with [Cr(CO)₃L₃] (L=NH₃, Py; cf. Schemes 3–6). Surprisingly, the off‐state complexes 17 and 19 , in which the Cr(CO)₃ group complexes on the diester ring, have been obtained with excellent regioselectivity. The directing effect of ester C=O groups on the regioselectivity of the Cr(CO)₃ coordination to heptalene rings has been discussed. These complexes undergo thermal rearrangements via 1,2‐intra‐ring shift and inter‐ring migration of the Cr(CO)₃ fragment to give the thermodynamically more stable on‐state complexes 16 and 27 , respectively (cf. Schemes 8 and 9). The analogous thermal behavior of other prepared complexes has also been investigated. A new procedure for the selective preparation of complexes 10 and 13 , in which the Cr(CO)₃ group is coordinated to the phenyl ring of the styryl substituent has also been developed (Scheme 7). The attachment of the Cr(CO)₃ fragment to the phenyl group has a visible influence on the UV/VIS behavior of the on‐state complexes 10 and 13a , as well as on the photochemical behavior of the DBS isomers 13a / 13b (cf. Scheme 10).     

A Spectroscopic Investigation of Donor‐Acceptor‐Substituted Heptalenes

It is shown that the heptalene‐4,5‐dicarboxylates 5 react with their Me group at C(1) with N,N‐dimethylformamide dimethyl acetal or other acetals of this type in N,N‐dimethylformamide (DMF) to give the corresponding 1‐[(E)‐2‐(N,N‐dialkylamino)ethenyl]‐substituted heptalene‐4,5‐dicarboxylates 8a – 8e as well as 8k and 8i in good yields (Table 1). In a similar manner, the 1‐[(E)‐2‐pyrrolidinoethenyl]‐substituted heptalene‐5‐carboxylates 8f – h were synthesized from the corresponding heptalene‐carboxylates 10 – 12 , carrying a CHO, CN, or (E)‐2‐(methoxycarbonyl)ethenyl group at C(4) (Table 1). All new heptalenes with the π‐donor and π‐acceptor groups at C(1) and C(4), respectively, exhibit a strongly enhanced heptalene band I in the spectral region of 450 – 500 nm in MeCN (Table 7 and Figs. 4 – 7), whereby the specific position is dependent on the π‐donor quality of the N,N‐dialkylamino substituent at C(2′) and the π‐acceptor property of the group at C(4). The position of heptalene band I is also strongly solvent‐dependent as is demonstrated in the case of heptalene 8i (Table 9). A good linear correlation with the CT band of 1‐(diethylamino)‐4‐nitrobenzene or (E)‐4‐(dimethylamino)‐β‐nitrostyrene (Figs. 11 and 12) characterizes the heptalene band I also as an electronic CT transition. Irradiation into this band of 8i leads, as observed in other cases (cf. [1]), to a double‐bond shift in the heptalene moiety (→ 8′i ; Figs. 8 – 10). On warming in solution, 8′i is converted quantitatively to 8i .