Transformation of Amides by Using an N-Alkoxy Group as a Reactivity Control Element

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K05436
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Organic chemistry
• Research Institution: Keio University
• Principal Investigator: Sato Takaaki 慶應義塾大学, 理工学部(矢上), 准教授 (70509926)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: アミド / 反応性制御素子 / 天然物合成 / 求核付加反応 / 求電子的アミノ化

Outline of Final Research Achievements

We developed a three-step synthesis of multi-substituted amines from N-alkoxyamides. Utilization of the N-alkoxy group as a reactivity control element was the key to success in this three-step synthesis. The first reaction was the N-alkoxyamide/aldehyde coupling reaction. The N-alkoxy group of amides enhanced the nucleophilicity of the nitrogen, enabling the direct coupling reaction. The second reaction was nucleophilic addition to the N-alkoxyamides. Incorporation of the N-alkoxy group into the amides increased the electrophilicity of the amide carbonyls and promoted the chelation effect. The third reaction was electrophilic amination using the resulting N-alkoxyamines. The developed method was applicable to a variety of substrates, resulting in the elaboration of multi-substituted amines including complex alkaloids such as fasicularin.

Free Research Field

有機化学