Exploration into New Synthetic Reactions Based on the Multi-Step Reactions with Conjugated Imines

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K05772
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Synthetic chemistry
• Research Institution: The Open University of Japan (2018); Mie University (2016-2017)
• Principal Investigator: Shimizu Makoto 放送大学, 三重学習センター, 特任教授 (30162712)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 極性転換反応 / α-イミノエステル / α-イミノチオエステル / α-ヒドラゾノエステル / α- N,N-ジアルキルアミノアミド / N,N,C-トリアルキル化反応 / タンデム求核付加反応

Outline of Final Research Achievements

We explored into new synthetic reactions using full potentiality of α-iminoesters their oxime and hydrazone analogues. An umpolung reaction to α-hydrazaonoesters was investigated, and it was found that α-N,N-dialkylaminoamides could be directly synthesized in high yields via a concomitant rearrangement of dialkylamino groups. Its asymmetric version was successfully carried out using α-hydrazaonoesters possessing a chiral auxiliary at their hydrazono moieties. As an application, a short-step synthesis of an inhibitor of glycine type-1-transporter was accomplished via further functional group transformations in good overall yield. α-N-Acyloxyimino esters served as highly efficient substrates for the electrophilic N,N,C-trialkylation reaction that could introduce various patterns of nucleophiles at the imino nitrogen and carbon atoms to synthesize N,N-dialkylated and N,N,C-trialkylated α-amino esters in moderate to high yields.

Free Research Field

化学

Academic Significance and Societal Importance of the Research Achievements

本研究は共役イミンへの極性転換反応であるN-アルキル化反応を基盤とし、それに引き続くタンデム求電子付加およびイミニウム塩への酸化を経るタンデム求核付加反応は、いずれも新規かつ高効率的反応集積化の手法であり、発展性も十分に兼ね備えている。これらの反応の有する四級α-アミノ酸誘導体合成の高いポテンシャルと、各種生理活性化合物を始めとするファインケミカルズ合成への応用性を考慮すると、本研究は効率的含窒素分子構築の分野の推進に大いに貢献できた。また、今まで曖昧な点が多く、論文等で殆ど記載されていなかったイミノ基のE,Z-立体化学と反応性との関係を明らかにすることができたことも、学術的に有意義である。