Construction of Unusual Indole-Based Heterocycles from Tetrahydro-1H-pyridazino[3,4-b]indoles

Herein, we report the successful syntheses of scarcely represented indole-based heterocycles which have a structural connection with biologically active natural-like molecules. The selective oxidation of indoline nucleus to indole, hydrolysis of ester and carbamoyl residues followed by decarboxylation with concomitant aromatization of the pyridazine ring starting from tetrahydro-1H-pyridazino[3,4-b]indole derivatives lead to fused indole-pyridazine compounds. On the other hand, non-fused indole-pyrazol-5-one scaffolds are easily prepared by subjecting the same C2,C3-fused indoline tetrahydropyridazine to treatment with trifluoroacetic acid (TFA). These methods feature mild conditions, easy operation, high yields in most cases avoiding the chromatographic purification, and broad substrate scope. Interestingly, the formation of indole linked pyrazol-5-one system serves as a good example of the application of the umpolung strategy in the synthesis of C3-alkylated indoles

Practical and sustainable preparation of pyrrolo[2,3-b]indoles by Cu/Fe catalyzed intramolecular C(sp2)–H amination

A practical, robust and chemoselective approach toward the synthesis of pyrrolo[2,3-b]indoles via direct intramolecular C–H bond amination of α-indolylhydrazones has been achieved. This base and oxidant-free chemoselective transformation relies on a Cu/Fe co-catalyst system that operates at 50 °C in air with water as the only reaction medium. The easy product isolation together with the recyclable catalyst aqueous system (reused at least five times, maintaining over 50% of its catalytic activity) can provide an effective environmentally benign approach to fused N-heterocycles of remarkable interest in pharmaceutical and medicinal chemistry. The ability of the hydrazone residue to act as a chelating/directing group as well as an aminating agent guarantees the success of this C–H functionalization

1,2-Diaza-1,3-butadienes: just a nice class of compounds, or powerful tools in organic chemistry? Reviewing an experience

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FeCl3-catalyzed formal [3 + 2] cyclodimerization of 4-carbonyl-1,2-diaza-1,3-dienes

none6noSubstituted 1-aminopyrroles are easily accessible by means of iron-catalyzed cascade reaction that requires as starting materials the solely 1,2-diaza-1,3-dienes. Mechanistically, the formal [3 + 2] cyclodimerization is hypothesized to proceed through a [4 + 2] cyclodimerization of 4-substitued 1,2-diaza-1,3-dienes followed by intramolecular ring closure to fused diaziridin-pyrrolines whose successive opening results in a ring contraction process with consequent generation of the pyrrole moiety. The presence of activated hydrogen in the terminal position of the azo-enic moiety is crucial for the success of the synthesis.openGiacomo Mari, Matteo Corrieri, Lucia De Crescentini, Gianfranco Favi, Stefania Santeusanio, Fabio MantelliniMari, Giacomo; Corrieri, Matteo; DE CRESCENTINI, Lucia; Favi, Gianfranco; Santeusanio, Stefania; Mantellini, Fabi

Synthesis of Azacarbolines via PhIO2‑Promoted Intramolecular Oxidative Cyclization of α‑Indolylhydrazones

An unprecedented synthesis of polysubstituted indolefused pyridazines (azacarbolines) from α-indolylhydrazones under oxidative conditions using a combination of iodylbenzene (PhIO2) and trifluoroacetic acid (TFA) has been developed. This transformation is conducted without the need for transition metals, harsh conditions, or an inert atmosphere

Experimental and theoretical DFT investigations in the [2, 3]-wittig-type rearrangement of propargyl/allyl-oxy-pyrazolones

Here we report the synthesis of interesting 3-alkyl-4-hydroxy-1-aryl-4-(propa-1,2-dienyl)1H-pyrazol-5(4H)-ones and 9-alkyl-7-aryl-1-oxa-7,8-diazaspiro[4.4]nona-3,8-dien-6-ones, starting from 1,2-diaza-1,3-dienes (DDs) and propargyl alcohol. The reaction proceeds through a sequence Michael-type nucleophilic attack/cyclization/[2,3]-Wittig rearrangement. In the same way, the reaction between the aforementioned DDs and allyl alcohol furnished 4-allyl-4-hydroxy-3-alkyl-1-aryl-1H-pyrazol-5(4H)-ones. A DFT study was also carried out, in order to have decisive clarifications about the mechanism