The present microreview summarizes our progresses over the last years in the chemistry of 1,2‐diaza‐1,3‐dienes. Beyond the findings reported here, the main target of this microreview is to outline some of the reactive peculiarities that make this class of compounds powerful tools in heterocyclic chemistry. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

A very simple domino reaction under solvent-free conditions of various pyridine-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 prefunctionalization of the starting heterocycles.

This paper reviews our nearly twenty-five years' activity on 1,2-diaza-1,3-butadienes and shows that these compounds are powerful tools in organic chemistry. In fact, α-substituted-, α-oxo-, and α,β-unsaturated-hydrazones, have been obtained from 1,2-diaza-1,3-butadienes, as have pyrroles,

A novel three-component synthesis of 5-hydrazinoalkylidene rhodanine derivatives starting from aliphatic primary amines, carbon disulfide, and 1,2-diaza-1,3-dienes is described. The reaction proceeds successfully under both solution and solid-phase conditions.

The synthesis of highly functionalized pyrroles is described. The sequence involves the preliminary preparation of a-aminohydrazones by Michael addition of primary amines to 1,2-diaza-1,3-butadienes. The treatment of these compounds with dialkyl acetylenedicarboxylates produces a-(Nenamino)-hydrazones that were converted into the corresponding pyrroles by Lewis acid-catalyzed ring closure. A screening of several Lewis/Brønsted acid catalysts was also performed.Keywords: alkynes; 1,2-diaza-1,3-butadienes; hydroamination; Lewis acids; Michael addition; pyrroles Pyrroles are among the most studied heterocyclic ring systems due to their diverse biological activities and applications in materials science. [1,2] As a consequence, much attention has been paid to their preparation by classical methods such as the Knorr, [3] Hantzsch, [4] and Paal-Knorr [5] syntheses. However, these approaches usually present significant limitations in terms of substituents that can be introduced, the substitution pattern, or regioselectivity. Several recent variations in the formation of pyrrole rings are based on metal-catalyzed reactions [6] and catalytic multicomponent coupling methodologies [7] which can improve usefully the classical synthetic approaches.We have demonstrated that the reactions between 1,2-diaza-1,3-butadienes and carbonyl compounds [8] or enol silyl derivatives [9] represent useful and convenient entries to 1-aminopyrroles. Here, we report a new and flexible Knorr-related strategy for the construction of amply functionalized pyrroles. The typical Knorr approach utilizes a-amino ketones and carbonyl derivatives containing an activated methylene group as starting materials.[3] A variation of this synthesis provides for the use of alkynes as reagents rather than carbonyl compounds.[10] In our methodology, the a-amino ketones are replaced with a-aminohydrazones. Their easy and flexible preparation involves the 1,2-diaza-1,3-butadienes 1a-d that readily react with different primary amines 2a, b in tetrahydrofuran at room temperature in the case of 1a-c, or under reflux for 1d producing the desired a-aminohydrazones 3a-f. The reaction takes place by means of 1,4-hydroamination (Michael-type) of the amino derivatives 2a, b to the azo-ene system of the 1,2-diaza-1,3-butadienes 1a-d. (Scheme 1, Table 1). [8b,11] It is noteworthy that a-aminohydrazones are solid compounds and are appreciably more stable to storage and handling than a-amino ketones. In fact, no self-condensation of compounds 3 was observed.In turn, the a-aminohydrazones 3a-f reacted with dialkyl acetylenedicarboxylates 4a-c in ethanol under reflux to give a-(N-enamino)-hydrazones 5a-i in 2-Scheme 1. Synthesis of the a-aminohydrazones 3a-f, and a-(N-enamino)-hydrazones 5a-i. i: THF, room temperature for 1a-c; THF, reflux for 1d. ii: EtOH, reflux.

The cycloadditions of (E)-3-diazenylbut-2-enes 1 with a variety of alkenes 2 ± 6 were carried out in water as well as in organic solvents. The reactions were always faster in heterogeneous aqueous medium than in the organic solvents. These conjugated diazenyl-alkenes behave mainly as heterodienes, and the Diels-Alder adducts are the sole or at least main reaction products. Pyrroles derived from zwitterionic [3 2] cycloaddition reactions were observed in some cases. The cycloaddition of 1a with ()-2-(ethenyloxy)-3,7,7-trimethylbicyclo[4.1.0]heptane (5) is the first example of an asymmetric inverse electron-demand Diels-Alder reaction carried out in pure water. 514 1 ) The configurations of diazenyl-alkenes 1a, 1b, and 1c were established by 1 H-NMR spectroscopy. The diazenyl-alkene 1d (R EtO, R 1 t-BuO) was chosen as the representative compound, because both diastereoisomers are available. In (Z) diazenyl-alkene, the saturation of HÀC(4) frequency gives a NOE effect on the H-atoms of the Me group (3%) and the saturation of frequency of the Me protons gives a NOE effect on HÀC(4) (5.4%). No NOE effect was observed on the (E)-stereoisomer. The chemical shifts of HÀC(4) and those of the MeÀC(3) group of the (E)-isomer are at lower field (d(HÀC(4)) 6.93 ppm; d(Me) 2.23 ppm) than those of the (Z)-isomer (d(HÀC(4)) 6.42 ppm; d(Me) 1.95 ppm). Accordingly, all diazenyl-butenes are (E)-configured. Scheme

The kinetics of the reactions of 1,2-diaza-1,3-dienes 1 with acceptor-substituted carbanions 2 have been studied at 20 °C. The reactions follow a second-order rate law, and can be described by the linear free energy relationship log k(20 °C)=s(N+E) [Eq. (1)]. With Equation (1) and the known nucleophile-specific parameters N and s for the carbanions, the electrophilicity parameters E of the 1,2-diaza-1,3-dienes 1 were determined. With E parameters in the range of -13.3 to -15.4, the electrophilic reactivities of 1a-d are comparable to those of benzylidenemalononitriles, 2-benzylideneindan-1,3-diones, and benzylidenebarbituric acids. The experimental second-order rate constants for the reactions of 1a-d with amines 3 and triarylphosphines 4 agreed with those calculated from E, N, and s, indicating the applicability of the linear free energy relationship [Eq. (1)] for predicting potential nucleophilic reaction partners of 1,2-diaza-1,3-dienes 1. Enamines 5 react up to 10(2) to 10(3) times faster with compounds 1 than predicted by Equation (1), indicating a change of mechanism, which becomes obvious in the reactions of 1 with enol ethers.

A sequential multicomponent reaction between ketoesters, isothiocyanates and 1,2-diaza-1,3-dienes to create 2,5-dihydrothiophenes that can be converted into thiophenes.