Intramolecular Alkene Aminocarbonylation Using Concerted Cycloadditions of Amino-Isocyanates

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• 作者：Ryan A. Ivanovich ; Christian Clavette ; Jean-Franç ; ois Vincent-Rocan ; Jean-Gré ; goire Roveda ; Dr. Serge I. Gorelsky and Prof. Dr. André ; M. Beauchemin
• 刊名：Chemistry - A European Journal
• 出版年：2016
• 出版时间：June 1, 2016
• 年：2016
• 卷：22
• 期：23
• 页码：7906-7916
• 全文大小：727K
• ISSN：1521-3765

文摘

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.