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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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

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

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

Divergent Construction of Pyrazoles via Michael Addition of N‑Arylhydrazones to 1,2-Diaza-1,3-dienes

partially_open4noThe base (NaH)-promoted Michael addition of N-arylhydrazones (AHs) with 1,2-diaza-1,3-dienes (DDs) produces unprecedented β-azohydrazone adducts. Strategically, the use of AHs as acyl anion equivalents (d1 synthon) and DDs as α-electrophiles (a2 synthon) of carbonyl compounds open the way to two important classes of pyrazole compounds.embargoed_20160409Serena mantenuto; Fabio Mantellini; Orazio Attanasi; Gianfranco FaviMantenuto, Serena; Mantellini, Fabio; Attanasi, ORAZIO ANTONIO; Favi, Gianfranc

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

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

A Novel Solvent-free Approach to Imidazole containing Nitrogen-Bridgehead Heterocycles

A very simple domino reaction under solvent free conditions of various piridine-like heterocycles with 1,2-diaza-1,3-dienes produces in good yields imidazo[1,2-a]pyridines, imidazo[1,2-a]quinolines and imidazo[2,1-a]isoquinolines. The advantage of this one-pot transformation lies in the use of simple pyridine-like compounds without pre-functionalization of the starting heterocycles

Synthesis of Novel Tryptamine Derivatives and Their Biological Activity as Antitumor Agents

We synthesized five novel tryptamine derivatives characterized by the presence of an azelayl chain or of a 1,1,1-trichloroethyl group, in turn connected to another heterocyclic scaffold. The combination of tryptamin-, 1,1,1-trichloroethyl- and 2-aminopyrimidinyl- moieties produced compound 9 identified as the most active compound in hematological cancer cell lines (IC50 = 0.57–65.32 M). Moreover, keeping constant the presence of the tryptaminic scaffold and binding it to the azelayl moiety, the compounds maintain biological activity. Compound 13 is still active against hematological cancer cell lines and shows a selective effect only on HT29 cells (IC50 = 0.006 M) among solid tumor models. Compound 14 loses activity on all leukemic lines, while showing a high level of toxicity on all solid tumor lines tested (IC50 0.0015–0.469 M)