4- Azaazulenes synthesis

Recently, cyclohepta[6]pyrrol-4-one derivatives were obtained as byproducts in the 1-azaazulene synthesis from 2-chlorotropone and 1-(diphenylphosphinyl)azaallyl anions [93H(36)2247],... 

Scheme 43. Synthesis of the 2-azaazulenes 131 from the Michael adducts 94 of DMPA-H to 1-Me [60]...

The Beckmann and Schmidt reactions are applicable to the synthesis of azepines fused to other heterocyclic and carbocyclic systems, such as pyridoazepinones (70JA203, 76AP550, 78JHC249), indoloazepinones (78CB1780) and the 14v aromatic azabenzazulen-nones (204) (80BCJ3232). The general chemistry of azaazulenes has been reviewed <81H(15)547>. 

Wittig reactions with pyrrole-2-aldehyde led to the esters (79) which were cyclisized to 3a-azaazulen-4-ones (80).104,105 4-Methylene-3a-aza-azulenes (81) have been obtained from 80 with stabilized phos-phoranes.36 Reaction of dimethyl acetylenedicarboxylate with 81 could not be achieved. A similar cycloaddition was successful in the synthesis of cycl[3,3,3]azines (2) (Section V). 

The 4-azaazulene 7i-system was first studied by G. Jones (68TL1935). A number of synthetic routes to unsaturated derivatives have been developed and selected derivatives have been used as starting materials for the synthesis of cyclazines (78AHC(22)321 84 HC-1). 

Treatment of perhydro-4-azaazulene (3) with mercuric acetate produces a mixture of dehydro derivatives 31a and 31b, which, with acids, yields homogeneous salts of structure 32 (56JOC344). The enamine 34, which was obtained by the same route from 33, served as a model compound in a study of the synthesis of cephalotaxine (72JOC3691). A reaction with ethyl y-bromo-acetoacetate surprisingly yielded the quinolizidine 36, which was formed by rearrangement of the intermediate annellation product 35 (Scheme 3) Phthalimides 38 were obtained from a Baeyer-Villiger oxidation of 4-azaazulen-3-ones 37 (77JOC1093). 

As shown in Section I, Clemmensen reduction of quinolizidin-1 -one (1) gave perhydroazaazulene (3) instead of the expected quinolizidine (2). The mechanism of this rearrangement has been studied and the reaction has been used for a synthesis of azaazulene derivatives (61 Mil). 

Azaazulen-3-one (5) and its benzo derivative (170) were obtained from A3-pyrroline-2-ones in a similar way (Scheme 15) (83MI1). Both of these 3-ones are highly colored and very unstable, in contrast to the isomeric 4-azaazulen-5-one (6), whose synthesis is shown in Scheme 16 (73CB1993). 

Two routes to 4-azaazulen-7-one (7) are known (Schemes 17 and 18). The crucial step of the first synthesis (Scheme 17) is the dehydrogenation of 171, which is difficult to control (82JCS(P1)1123). Dehydrogenation is avoided in the second synthesis (Scheme 18), which allows an easy preparation of the azaazulenone 7 on a large scale (86MI1). 

The synthesis of 4-azaazulen-9-one (8) is shown in Scheme 19. The final cyclization could be achieved in boiling quinoline as well as by flash vacuum pyrolysis. Interestingly, only the parent compound 8 was obtained. Attempts to synthesize a methyl derivative of 8 by thermolysis of 172b led to the pyrrole 173 (78CB2407). 

Azaazulenes, reactivity and synthesis of 81H(15)547, 81YGK690. Azadienes, heterocyclic, Diels-Alder reactions of 86CRV781. 

The intramolecular aza-Wittig reaction has been described previously as a convenient route for the synthesis of azepines, and, in a bimolecular equivalent, the reaction of 2-formyl-6-dimethyl-aminofulvene with phenyl-substituted vinyliminophosphoranes in a one-pot reaction offers a facile synthesis of phenyl-substituted 5-azaazulene (201) <91TL6727>. 

Kiewel, K., Tallant, M. and Sulikowski, G.A. (2001) Asymmetric Heck cyclization route to indolizidine and azaazulene alkaloids synthesis of (+)-5-epiindolizidine 167B and indolizidine 223AB. Tetrahedron Lett., 42, 6621-3. 

Synthesis of Heterocycles. TMSK has also gained prominence as a useful reagent for accessing various heterocycles. TMSK reacts readily with aA -diarylnitrones to afford N-alkyloxindoles, which can subsequently be converted to oxindoles upon hydrolysis (eq 19). The analogous ring expanded 3,3a-dihydro-3-trimethylsilyl-l-azaazulen-2(lH)-ones can also be accessed via an [8 + 2] cycloaddition of TMSK with 8-azahepta-fulvenes.4 ... 

A short new synthesis of 1-azaazulene derivatives 496 consists in the alkylation oftroponimines 497 with pyrrolidino enamines 498, as reported by Nitta s group. The reaction leads to formal [8+2] cycloadducts 499, and subsequent aromatiza-tion takes place under the reaction conditions (Scheme 6.131) [296]. In this transformation, pyrrolidino enamines are required, probably because of ring strain in the [8+2] cycloadduct 499. 

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