The rapid and expedient assembly of three new classes of biheterocycles of biological interest, viz. indole–imidazoles 4, indole–pyrroles 6 and indole–triazoles 8 was accomplished using different combinations of tryptamines, 1,2‐diaza‐1,3‐dienes, aldehydes, and/or alkynes as readily available building blocks. Twenty‐six derivatives were thus prepared in excellent yields (up to 100 %). The products were screened for in‐vitro biological studies. Some of these revealed promising anticancer activity against MCF7 and Caco‐2 human tumor cell lines.

A Pd(II)-catalyzed intramolecular oxidative C-H/C-H cross-coupling has been developed for the direct construction of valuable polycyclic heteroarene scaffolds. From a retrosynthetic point of view, the strategic formation of a C-C bond via C(sp)-H/C(sp)-H dehydrogenative coupling across C3,N-linked biheterocyclic precursors may be useful in de novo syntheses of indole-derived natural products and pharmaceuticals. The reaction exhibited good functional group/heterocycle tolerance, and a proposed mechanism involving an azoylpalladium complex is also supported.

In situ derived acyclic and cyclic 1,2-diaza-1,3-dienes (DDs) were engaged in interceptive [4 + 1] annulation strategy with diazo esters (DEs). The catalytic activity of inexpensive copper(II) chloride allows the direct synthesis of mono-, bi-, and tricyclic 4,5-dihydropyrazole-5-carboxylic acid derivatives in a process that circumvents the use of an anhydrous and inert atmosphere.

The 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 (d(1) synthon) and DDs as α-electrophiles (a(2) synthon) of carbonyl compounds open the way to two important classes of pyrazole compounds.

Abstract:The multicomponent 1,3-dipolar cycloaddition of different 1,2-diaza-1,3-dienes with in situ-generated azomethine ylides produces 1,2,4-triazepines or pyrrolidines by means of [3+4] or [3+2] cycloadditions, respectively. The regioselectivity is controlled by the electron-withdrawing group bound to the azo-moiety of the 1,2-diaza-1,3-diene which promotes exclusively the [3+4] cycloaddition. When the electron-withdrawing group is replaced with a phenyl group only a [3+2] cycloaddition occurs.