Synthesis of Biologically Active Heterospirocycles through Iterative 1,3-Dipolar Cycloaddition Pathways.

We demonstrate the novel spiroannulation of exo-imines with 1,3-dipoles, for the first time, leading to 3D spirocycles with a secondary amine (NH) in the spiro-ring. The synthetic method described herein allows access to these previously unexplored heterospirocyclic cores that have application in the discovery of functional molecules for medicinal and materials science. This was demonstrated by discovering an unprecedented class of heterospirocycles with antimalarial activity against the human protozoan P. falciparum.

Synthesis of 1,2,4-Triazol-3-imines via Selective Stepwise Cycloaddition of Nitrile Imines with Organo-cyanamides.

A convenient method for the synthesis of 1,2,4-triazol-3-imines through a selective, formal, 1,3-dipolar cycloaddition of organo-cyanamide ions with nitrile imine dipoles is reported. Hydrolysis of the 1,2,4-triazol-3-imines yields the corresponding 1,2,4-triazol-5-ones. A stepwise mechanism, supported by DFT calculations, is invoked to explain the reaction selectivity.

Recent Advances in Cyanamide Chemistry: Synthesis and Applications.

The application of alkyl and aryl substituted cyanamides in synthetic chemistry has diversified multi-fold in recent years. In this review, we discuss recent advances (since 2012) in the chemistry of cyanamides and detail their application in cycloaddition chemistry, aminocyanation reactions, as well as electrophilic cyanide-transfer agents and their unique radical and coordination chemistry.

Synthesis of Oxadiazol-5-imines via the Cyclizative Capture of in Situ Generated Cyanamide Ions and Nitrile Oxides.

An unprecedented intermolecular cyclizative capture of the cyanamide anion and several nitrile oxides enables the synthesis of oxadiazol-5-imines.