Development of novel multi-component synthesis of 1,4-dihydropyridines by auto-tandem catalysis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08207
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: University of Toyama
• Principal Investigator: Sugimoto Kenji 富山大学, 学術研究部薬学・和漢系, 准教授 (60400264)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ジヒドロピラゾール / ジヒドロピリジン / アザブタジエン / カチオン性金触媒 / オートタンデム触媒

Outline of Final Research Achievements

As an extension of our previous report on the azomethine ylide formation from glycine iminoesters and acetylenes, we attempted a construction of azomethine imines from aryl carbazates and acetylenes; however, we unexpectedly found a novel gold auto-tandem catalysis including aza-enyne metathesis, hydroamination of resultant 1-azabutadiene, and 6p-electrocyclization to form multi-substituted dihydropyrazoles. Furthermore, we revealed such aza-enyne metathesis was also induced from aryl imines to afford highly substituted 1,4-dihydropyridines through 1-azabutadienes by gold auto-tandem catalysis including aza-enyne metathesis followed by [4+2]-cycloaddition with the other acetylenes.
Until now, we attempted a construction of substituted pyridines from oximes by our catalysis and could observe a similar aza-enyne metathesis to form the desired azabutadienes. Further transformation of the N-alkoxy-1-azabutadienes is now in progress.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

これまでに報告例の少ないアザエニンメタセシスが金触媒によって収率良く進行する条件を見いだすことができ、生じた1-アザブタジエンが同一の金触媒によって更なる変換を受けて、ジヒドロピラゾール、ジヒドロピリジンを生成するという新たな分子変換法を確立することができた。学術的な新知見であるとともに、同一触媒を一つの反応容器中で複数の変換に利用するという高効率的な手法を確立することで、医薬品等の高機能化合物の簡便提供法への展開など高い社会還元性が期待される。