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

Abstract

A number of azulenes 1, in particular those with p-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 1108 (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 p-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.

Dyotropic Rearrangements of Dihalogenated Hydrocarbons: A Density Functional Theory Study

“…10 Moreover, some of them provide synthetic utility. [11][12][13][14] For example, the dyotropic shift of 4-cyclohexyl β-lactone to 7-oxaspiro [5,4]decan-8-one has been demonstrated to be a facile route in the synthesis of spiro butyrolactones, a pharmacologically important subunit in a number of naturally occurring products and in several drugs. 11,15,16 Although the orbital symmetry rules established by Woodward and Hoffmann 17 have contributed much to our understanding of the mechanisms of dyotropic shifts, 10 they are incapable of providing quantitative information.…”

“…Reactions of this type have enriched our knowledge of orbital symmetry conservation of concerted processes . Moreover, some of them provide synthetic utility. − For example, the dyotropic shift of 4-cyclohexyl β-lactone to 7-oxaspiro[5,4]decan-8-one has been demonstrated to be a facile route in the synthesis of spiro butyrolactones, a pharmacologically important subunit in a number of naturally occurring products and in several drugs. ,, Although the orbital symmetry rules established by Woodward and Hoffmann have contributed much to our understanding of the mechanisms of dyotropic shifts, they are incapable of providing quantitative information. Theoretical calculation permits us to obtain a desirably revealing picture of a chemical reaction and has been applied successfully to predict the structure of transition states and the configuration of products for numerous sigmatropic rearrangements.…”

The Synthetic Versatility of Acyloxyborohydrides

“…Aryl ketones that can form relatively stable carbocationslike their monobenzylic alcohol counterparts (vide supra)can be reduced to the corresponding methylene compounds. For example, azulene aldehydes ( 47 and 49 ) are converted to 48 and 50 , respectively . Both carbonyl groups in 51 are reduced to biindole 52 , and the monoactivated ketone in methyl pyropheophorbide-a is reduced to methylene in 75% yield .…”

“…The early discovery that NaBH 3 CN/CF 3 CO 2 H reductively cleaves acetals has been employed in the synthesis of disaccharides , ( 55 → 56 ) . Interestingly, aminal 57 is cleaved to 58 , maintaining the acetal unit, but in the azulene work cited earlier 141 some of the dimethylthioacetal azulene is reduced with NaBH 4 /CF 3 CO 2 H 141b. Oxazolidines are easily cleaved ( 59 → 60 ), and this tactic was featured in the first enantiospecific synthesis of salinosporamide A …”

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

“…To a cold soln. (08) of dimethyl 8-isopropyl-5-methylheptalen-4,5-dicarboxylate (960 mg, 2.94 mmol; prepared from 6-isopropyl-1-methylazulene and ADM [20]) in THF (80 ml), a ca. 1m (i-Bu) 2 AlH soln.…”