Transition-metal catalyzed Crouss-coupling of hydrazone via novel synthetic intermediate

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23815
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: Kobe Pharmaceutical University
• Principal Investigator: YASUI Motohiro 神戸薬科大学, 薬学部, 助教 (30845912)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: C-H活性化 / C-H官能基化 / パラジウム / ヒドラゾン / 配向基 / シクロプロパン / ヘテロ環 / 含窒素

Outline of Final Research Achievements

C-H alkynylation reaction of aldohydrazones on the carbon center of hydrazone has been found. This finding can be expected to develop the synthesis of alkynyl hydrazone derivatives in a stereoselective manner, which has been difficult to realize so far. In addition, a pyrazole synthetic method has been developed via C-H activation of N-cyclopropyl-C-acyloxyhydrazones. Some control experiments suggest that the reaction progresses through a novel paradacycle. Therefore, creating a novel directing group, the nitrogen atom in which is incorporated to a forming heterocycle, to cleavage unactivated C-H bond of cyclopropanes has been succeeded.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

不活性な結合を選択的に切断して反応活性な化学種を生成する手法の開発は、従来の化学合成の手法を刷新し、合成効率の向上や新規ビルディングブロックの創出へと繋がる。本研究ではヒドラゾンを有する基質の不活性C-H結合を選択的に切断し、新奇反応活性種の存在を確認することに成功した。得られた知見から、これまで合成困難だったヒドラジンやヒドラゾンの革新的合成法の開発へと展開できる。このことは、昨今の医薬品開発において必要不可欠な三次元ビルディングブロックの迅速供給へと繋がる。