Ring-breaking Fluorination of Heteroarenes

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K18966
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 33:Organic chemistry and related fields
• Research Institution: Waseda University
• Principal Investigator: Junichiro Yamaguchi 早稲田大学, 理工学術院, 教授 (00529026)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: フッ素化 / アジン / 求電子剤 / ピラゾロピリジン / イソオキサゾール

Outline of Final Research Achievements

Fluorination reactions, which involve introducing fluorine into molecules, have become one of the most crucial reactions in recent years for enhancing the functionality of molecules in drug discovery. Numerous (asymmetric) fluorination reactions have been developed in recent years. However, most of these methods focus on introducing fluorine into the existing molecular framework, with few reports on methods that introduce fluorine while altering the framework. In this study, we discovered an open-ring fluorination reaction that cleaves hetero-hetero bonds in heteroaromatic rings and introduces fluorine while opening the ring. The products obtained from this reaction are not fluorine-substituted aromatic compounds but tertiary fluorinated compounds, representing a new type of fluorination reaction involving skeletal transformation.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

本反応は芳香族化合物のフッ素化反応ではあるが、得られる生成物は芳香族化合物のフッ素置換体ではなく、第三級フッ素化合物であり、骨格変換を伴う新形式のフッ素化反応といえる。開環型フッ素化反応は最近報告されているが、（ヘテロ）芳香環ではこの反応が初の例となった。また生成物はヘテロ環、シアノ基を含んでおりメディシナルケミストリーにおいても魅力的な合成中間体であると考えている。