Alessandra Casnati

The hydroamination reaction1 consists in the nucleofilic addition of a nitrogen on an unsaturated compound. The intrinsic challenge in this methodology is the repulsion between a nitrogen lone pair and the π-system combined to the regioselectivity problems towards the Markovnikov and anitMarkovnikov products.

Moreover this method represents a powerful tool for the synthesis of enamine-containing heterocyclic compounds. This scaffold is present in a wide amount of natural and synthetic molecules that exhibit interesting physiological and biological activities2.
Among these naturally occurring products imidazole-2-ones and imidazolidin-2-ones are known to exploit anti-carciogenic, anti-bacterial, anti-fungal, anti-microbial activities3; they have been used as intermediates in the synthesis of many natural products as biotin or alkaloids derivatives.4

We report the first efficient organo-catalyzed protocol for the intramolecular hydroamination/cyclization reaction of propargylic ureas for the synthesis of imidazol-2-ones and imidazolidin-2-ones. This organo-catalyzed methodology features a high functional group tolerance and gives access to richly decorated imidazolidinone derivatives.

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