Cascade reactions of nitrogen-substituted isocyanates: a new tool in heterocyclic chemistryElectronic supplementary information (ESI) available: Complete experimental procedures, characterization data, and NMR spectra. CCDC 1420522 and 1420523. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5sc03197d

• Main Authors: Vincent-Rocan, Jean-François, Ivanovich, Ryan A, Clavette, Christian, Leckett, Kyle, Bejjani, Julien, Beauchemin, André M
• Format: Journal Article
• Published: 14.12.2015
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c5sc03197d

In contrast to normal C -substituted isocyanates, nitrogen-substituted isocyanates ( N -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 in situ formation approach using a reversible equilibrium, which allows controlled generation and reactivity of N -isocyanates and prevents the dimerization that is typically observed with these intermediates. This blocked (masked) N -isocyanate approach enables the use of various N -isocyanate precursors to assemble heterocycles possessing the N-N-C&z.dbd;O motif, which is often found in agrochemicals and pharmaceuticals. Cascade reactions for the rapid assembly of several valuable 5- and 6-membered heterocycles are reported, including amino-hydantoins, acyl-pyrazoles, acyl-phthalazinones and azauracils. Over 100 different compounds were synthesized using amino-, imino- and amido-substituted N -isocyanates, demonstrating their potential as powerful intermediates in heterocyclic synthesis. Their reactivity also enables access to unprecedented bicyclic derivatives and to substitution patterns of azauracils that are difficult to access using known methods, illustrating that controlled reactivity of N -isocyanates provides new disconnections, and a new tool to assemble complex N-N-C&z.dbd;O containing motifs. Rare and amphoteric intermediates, in situ generation: controlled reactivity in diverse cascade reactions, over 100 examples.