Cascade reactions of nitrogen-substituted isocyanates: a new tool in heterocyclic chemistry.

In contrast to normal -substituted isocyanates, nitrogen-substituted isocyanates (-isocyanates) are rare. Their high reactivity and amphoteric/ambident nature has prevented the scientific community from exploiting their synthetic potential. Recently, we have developed an formation approach using a reversible equilibrium, which allows controlled generation and reactivity of -isocyanates and prevents the dimerization that is typically observed with these intermediates.

A cascade synthesis of aminohydantoins using in situ-generated N-substituted isocyanates.

Nitrogen-substituted isocyanates are rarely utilized but powerful building blocks for the development of cascade reactions in heterocyclic synthesis. These reactive amphoteric intermediates can be accessed in situ via an equilibrium that allows controlled reactivity in the presence of bifunctional partners such as α-amino esters. A cascade reaction has been carried out that forms 3-aminohydantoin derivatives using simple phenoxycarbonyl derivatives of hydrazides and hydrazones as precursors of N-substituted-isocyanates.