title: One-Pot Synthesis of Aza-Diketopiperazines Enabled by Controlled Reactivity of N-Isocyanate Precursors.
abstract: A one-pot sequence for the synthesis of aza-diketopiperazines is reported, involving carbazate acylation with chloroacetyl chloride, SN2 with a primary amine, N-isocyanate formation, and cyclization. Nitrogen-substituted isocyanates (N-isocyanates) are a rare class of amphoteric isocyanate with high, but severely underdeveloped synthetic potential. This approach highlights that βN-acyl carbazates can act as blocked (masked) N-isocyanates, thus allowing a challenging intermolecular SN2 reaction of a primary amine to proceed while the N-isocyanate is "protected", and then cyclization once it is unmasked. Control experiments show that the alternate pathway--N-isocyanate substitution and then cyclization by an intramolecular SN2 reaction--is not operating.
authors.affiliation: Centre for Catalysis Research and Innovation, Department of Chemistry and Biomolecular Sciences, University of Ottawa , 10 Marie-Curie, Ottawa, ON K1N 6N5, Canada.
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Ivanovich
authors.affiliation: Centre for Catalysis Research and Innovation, Department of Chemistry and Biomolecular Sciences, University of Ottawa , 10 Marie-Curie, Ottawa, ON K1N 6N5, Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Vincent-Rocan
authors.affiliation: Centre for Catalysis Research and Innovation, Department of Chemistry and Biomolecular Sciences, University of Ottawa , 10 Marie-Curie, Ottawa, ON K1N 6N5, Canada.|Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University , Cairo 11884, Egypt.
authors.forename: Eslam B
authors.initials: EB
authors.lastname: Elkaeed
authors.affiliation: Centre for Catalysis Research and Innovation, Department of Chemistry and Biomolecular Sciences, University of Ottawa , 10 Marie-Curie, Ottawa, ON K1N 6N5, Canada.
authors.forename: André M
authors.initials: AM
authors.lastname: Beauchemin