Francesca R. Perrulli

Copper(II)/Copper(I)-Catalyzed Aza-Michael Addition/Click Reaction of in Situ Generated α-Azidohydrazones: Synthesis of Novel Pyrazolone−Triazole Framework

A one-pot Cu(II)-catalyzed aza-Michael addition of trimethylsilyl azide to 1,2-diaza-1,3-dienes and Cu(I)-catalyzed 1,3-dipolar cycloaddition of in situ generated alpha-azidohydrazones with alkynes is reported. This process combining two consecutive steps with recycling of the catalyst (Cu(OAc)(2).H(2)O) represents a useful protocol for the smooth synthesis of novel pyrazolone-triazole derivatives.

A Novel and Convenient Protocol for Synthesis of Pyridazines

A new flexible strategy for the synthesis of diversely functionalized pyridazines from 4-chloro-1,2-diaza-1,3-butadienes and active methylene compounds is reported. The high chemoselectivity of this approach offers access to structural precursors of GABA-A antagonist analogues.

Powerful approach to heterocyclic skeletal diversity by sequential three-component reaction of amines, isothiocyanates, and 1,2-diaza-1,3-dienes.

By highly efficient, one-pot, three-component reactions, combining one set of 1,2-diaza-1,3-dienes (DDs), primary amines, and isothiocyanates in a different sequential order of addition, heterocyclic skeletal diversity can be achieved. The key feature discriminating the different heterocyclic core formation is the availability of the N or S heteronucleophile to give the first Michael addition step affording regioselective substituted 2-thiohydantoins or 2-iminothiazolidinones. The hydrazone or enehydrazino side chain at the 5-position of both heterocycles represents a valuable functionality to reach novel 5-hydroxyethylidene derivatives difficult to obtain by other methods.

Tandem Aza-Wittig/Carbodiimide-Mediated Annulation Applicable to 1,2-Diaza-1,3-dienes for the One-Pot Synthesis of Fully Substituted 1,2-Diaminoimidazoles

One-pot sequential aza-Michael, Staudinger, and aza-Wittig reactions on 1,2-diaza-1,2-dienes (DDs) can afford fully substituted 1,2-diaminoimidazoles. A plausible mechanism for the imidazole core formation involving an intramolecular ring closure of the carbodiimide-derived phosphazene intermediate is given. The reported strategy has sufficient flexibility to allow substituted 1,2-diaminoimidazoles with orthogonal nitrogen-protective groups to be generated from a variety of heterocumulene moieties linked to the DDs skeleton.

Regioselective role of the hydrazide moiety in the formation of complex pyrrole–pyrazole systems

Abstract The treatment of alkyl 2-chloroacetoacetate with ethyl 3-hydrazino-3-oxopropionate, (4-chlorobenzenesulphonyl)acetic acid hydrazide, 4-nitrophenylacetic acid hydrazide, phenylacetic acid hydrazide, thiophene-3-acetic acid hydrazide or indole-3-acetic acid hydrazide leads to the corresponding hydrazone derivatives. In the presence of sodium carbonate, these compounds react at room temperature with acetoacetanilide or 2,4-pentanedione to give the corresponding 1-aminopyrrole rings through the relevant 1,2-diaza-1,3-butadiene intermediates. In the presence of sodium methoxide, the activated methylene group present on the 1-amino side chain of the heterocycles obtained from ethyl 3-hydrazino-3-oxopropionate or 4-nitrophenylacetic acid hydrazide attacks at room temperature 1,2-diaza-1,3-butadienes affording the respective hydrazonic 1,4-adducts. Under basic conditions, these adducts cyclise at room temperature providing NH CO CH-bridged pyrrole–pyrazole systems. In the case of (4-chlorobenzenesulphonyl)acetic acid hydrazide, the corresponding 1-aminopyrrole does not add a further molecule of 1,2-diaza-1,3-butadiene giving rise to 1 H -pyrrole and 2-oxohydrazone derivatives as identified compounds. Under the same reaction conditions, the NH group of 1-aminopyrroles derived from phenylacetic acid hydrazide, thiophene-3-acetic acid hydrazide or indole-3-acetic acid hydrazide adds at room temperature 1,2-diaza-1,3-butadienes producing another type of hydrazonic 1,4-adduct. Under basic conditions, these adducts cyclise at room temperature giving rise to different N-bonded pyrrole–pyrazole systems.

1,2-Diaza-1,3-Butadienes: A New Approach to the Synthesis of Selenoheterocycles

1,2-Diaza-1,3-butadienes react easily with selenoureas to produce 2-selenazolin-4-one derivatives and with selenobenzamide to afford 2-selenazoline derivatives, the stereochemistries of which were determined. Whereas 2-selenazoline derivatives of 4R*,5R* configuration undergo aromatization under basic conditions, 2-selenazolin-4-ones, under different reaction conditions, appear to be attractive entry compounds to conjugated azoalkenes, 5,5-disubstituted selenazolin-4-ones, and spiro-condensed heterocyclic systems including selenazolinone rings. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Reactions of 1,2-diaza-1,3-butadienes with propargyl alcohol as an approach to novel bi-heterocyclic systems

Here we describe the reaction of 1,2-diaza-1,3-dienes and propargyl alcohol furnishing α-(prop-2-yn-1-yloxy)hydrazones that are converted into novel alkyl-1-oxa-7,8-diazaspiro[4.4]nona-3,8-dien-6-ones, by means of 2,3-Wittig rearrangement under very mild conditions. The same α-(prop-2-yn-1-yloxy)hydrazones, treated with benzyl azides furnish the corresponding α-[(1,2,3-triazol-4-yl)methoxy]hydrazones, via Cu(ii)-catalyzed 1,3-dipolar cycloaddition. Their subsequent base-promoted cyclization produces interesting pyrazolone-triazole derivatives. The impact of this work can be ascribable to the attractiveness of the bi-heterocyclic systems obtained and to the ease of the synthetic methodologies proposed.

Divergent Approach to Thiazolylidene Derivatives: A Perspective on the Synthesis of a Heterocyclic Skeleton from β-Amidothioamides Reactivity

Herein we report a domino protocol able to reach regioselectively thiazolylidene systems by combining the reactive peculiarities of both β-amidothioamides (ATAs) and 1,2-diaza-1,3-dienes (DDs). Depending on the reaction conditions and/or the nature of the residue at C4 of the heterodiene system, ATAs can act as hetero-mononucleophiles or hetero-dinucleophiles in the diversified thiazolylidene ring assembly.

Cleavage and reactions of some NH-BOC protected 1-aminopyrroles: a newone-pot route to pyrrolo[1,2-b][1,2,4]triazines together withspectroscopic and X-ray studies

1-NH-BOC protected 1,2-diaminopyrroles have been converted by one-pot cleavage of the protecting group and subsequent reaction of the compounds obtained with 1,2-dicarbonyl compounds into highly substituted pyrrolo[1,2-b][1,2,4]triazines. Structural assignments to the regioisomers arising from the reaction with phenylglyoxal have been made on the basis of NMR spectral evidence. An X-ray crystal structure analysis of 6-ethoxycarbonyl-7-methyl-3-phenyl-5-piperidin-1-ylcarbonylpyrrolo[1,2- b][1,2,4]triazine has been carried out in order to confirm unambiguously the structure assignment.

Simple Direct Synthesis of New 1-Heterocyclamino-3-Carbonylaminopyrroles by Reaction of Heterocyclic Azoalkenes with β-Ketoamides

Abstract Pyrrole and several its derivatives have been subjected to extensive chemical investigations, while substituted 1-aminopyrroles remain a class of compounds about which relatively little is known due to the far from trivial problem sposed by their syntheis. In fact, 1-aminopyrroles appear to be prepared mainly by direct reactionfrom conjugated azoalkenes,2 that unfortunately represent a class of relatively little