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

Herein we report a domino protocol able to reach regioselectively thiazolylidene systems by combining the reactive peculiarities of both ß-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.

Access to novel imidazo[1,5-a]pyrazine scaffolds by the combined use of a three-component reaction and a base-assisted intramolecular cyclization.

A novel and practical two-step approach to an intriguing class of imidazo[1,5-a]pyrazines with exocyclic C=X (X = CH2, O) bonds is described. The process utilizes a sequential three-component reaction of propargyl amine or aminoester, 1,2-diaza-1,3-dienes and isothiocyanates to furnish functionalized 2-thiohydantoins which are transformed into thiohydantoin-fused tetrahydropyrazines by subsequent regioselective base-promoted cyclization.

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.

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.

1,3,5-Trisubstituted and 5-acyl-1,3-disubstituted hydantoin derivatives via novel sequential three-component reaction.

1,2-Diaza-1,3-dienes (DDs) react as Michael acceptors with primary amines to afford α-aminohydrazone derivatives that were in situ coupled with isocyanates. Intramolecular ring closure of the asymmetric urea derivatives so formed allows for a selectively substituted hydantoin ring to be obtained. The hydrazone side chain introduced by the conjugated heterodiene system at the 5-position of the heterocycle represents a valuable functionality for accessing novel 5-acyl derivatives difficult to obtain by other methods.