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Intramolecular Alkene Aminocarbonylation Using Concerted Cycloadditions of Amino‐Isocyanates
Author(s) -
Ivanovich Ryan A.,
Clavette Christian,
VincentRocan JeanFrançois,
Roveda JeanGrégoire,
Gorelsky Serge I.,
Beauchemin André M.
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201600574
Subject(s) - alkene , hydroamination , chemistry , isocyanate , intramolecular force , reactivity (psychology) , combinatorial chemistry , carbonylation , organic chemistry , amination , catalysis , polyurethane , medicine , alternative medicine , pathology , carbon monoxide
The ubiquity of nitrogen heterocycles in biologically active molecules challenges synthetic chemists to develop a variety of tools for their construction. While developing metal‐free hydroamination reactions of hydrazine derivatives, it was discovered that carbazates and semicarbazides can also lead to alkene aminocarbonylation products if nitrogen‐substituted isocyanates ( N ‐isocyanates) are formed in situ as reactive intermediates. At first this reaction required high temperatures (150–200 °C), and issues included competing hydroamination and N ‐isocyanate dimerization pathways. Herein, improved conditions for concerted intramolecular alkene aminocarbonylation with N ‐isocyanates are reported. The use of βN ‐benzyl carbazate precursors allows the effective minimization of N ‐isocyanate dimerization. Diminished dimerization leads to higher yields of alkene aminocarbonylation products, to reactivity at lower temperatures, and to an improved scope for a reaction sequence involving alkene aminocarbonylation followed by 1,2‐migration of the benzyl group. Furthermore, fine‐tuning of the blocking (masking) group on the N ‐isocyanate precursor, and reaction conditions relying on base catalysis for N ‐isocyanate formation from simpler precursors resulted in room temperature reactivity, consequently minimizing the competing hydroamination pathway. Collectively, this work highlights that controlled reactivity of aminoisocyanates is possible, and provides a broadly applicable alkene aminocarbonylation approach to heterocycles possessing the β‐aminocarbonyl motif.