Aniline derivatives heterocyclic synthesis, intramolecular

There have been several reports of the use of intramolecular displacements of nitro groups in the synthesis of heterocyclic compounds. Thus, reaction16 of the intermediate (2) with a strong base in DMF results in the substitution of a nitro group by the amide function to yield a dibenzothiazepinone derivative (3). Nucleophilic addition across the double bond of 2,4,6-trinitrostyrene may occur with thiophenol, aniline, and aliphatic amines. The adducts so formed with primary amines may undergo intramolecular substitution of an o-nitro group to give IV-substituted 4,6-dinitroindoles.17... 

There are numerous reports of hydrofonnylation reactions where an amine substituent in the substrate condenses with the aldehyde product to form a heterocyclic ring (Fig. 6). Intramolecular hydroaminomethylation reactions are often referred to as cyclohydrocarbonylation reactimis. A Cbz-protected homoallylic amine underwent cyclohydrocarbonylatiOTi with Rh-biphephos to form the natural product, ( )-coniine (Fig. 6, 13) [25]. Alper recently reported the formation the seven-membered ring of 2-benzazepines (Fig. 6, 14) by hydroformylation of 2-isopropenylbenzaldehydes in the presence of anilines [26]. Intramolecular hydroaminomethylation of 2-isopropenylanilines produces 1,2,3,4-tetrahydroquinolines (Fig. 6, 15) [27]. In some instances, the enamine derived from intramolecular condensation of the resulting aldehyde is desired. For example, the synthesis of a key intermediate (Fig. 6,16) in the synthesis of a series of ACE inhibitors was... 

An interesting tandem intermolecular/intramolecular hydroamination reaction of cycloheptatriene with substituted anilines has been developed by Hartwig for the synthesis oftropene derivatives [34]. As shown in Eq. (1.14), the coupling of 30 with 31 provided 32 in 73% yield. The mechanism of this transformation is believed to involve acid-assisted formation of an q -pentadienylpalladium complex 33, which is then captured by the aniline nucleophile to afford the allylpalladium intermediate 34. Intramolecular attack of the aniline nitrogen on the allylpalladium moiety affords the observed heterocycle. 

Carbazoles are pharmaceutically important heterocycles, and are attractive targets for organic chemists. Carbazole alkaloids are natural products exhibiting antitumor, antibacterial, antimicrobial, and antiinflammatory activities. Some carbazole derivatives display photoconducting and semiconducting properties. The nucleophylic approach can be used for the synthesis of the carbazole core. For example, intramolecular cyclization of 2-(6-substituted-3-(Z)-hexene-l,5-diyne)anilines 3.702 was accomplished for the synthesis of 5-carbazoles 3.703 in 65-85% yield (Scheme 3.76) [331]. 

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