Development of Chiral Ligand Containing Indazole Ring and Its Application to Dynamic Kinetic Resolution

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K06560
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
• Research Institution: Musashino University
• Principal Investigator: Hiroya Kou 武蔵野大学, 薬学部, 教授 (70192721)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 不斉配位子 / インダゾール / カチオン性パラジウム錯体 / ベンザイン / クロスカップリング / 二座配位子

Outline of Final Research Achievements

The purpose of this research has been established the development of the chiral ligand containing indazole ring system. The ligand, which has oxygen atom and nitrogen atom in indazole ring as ligation atoms, was synthesized with some racemization. But it did not work well for chiral induction during the allylation reactions. Next, we successfully synthesized the ligand, which has phosphorus atom and nitrogen atom in indazole ring as ligation atoms. However, it was impossible to keep high level optical purity during synthesizing the ligands. Therefore, we designed new type compounds having the asymmetric center at beta position of the nitrogen atom in the indazole ring and it was successfully synthesized by short steps. The confirmation of this ligand and the optimization of the structure is underway.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

インダゾール環は2位の窒素原子上の非共有電子対が求核性・塩基性をもっているために，特異な化学的性質を有しているが，この性質を利用した機能性物質開発はほとんど報告されていない．本研究では，効率的なインダゾール環構築反応を利用して，迅速に必要な骨格を構築することに成功した点は学術的に意義があったものと考えている．しかし，高い光学純度を保ちながら，不斉炭素を有するアルキル基の導入は困難であった．新たにデザインした化合物は，当初予定していた化合物より不斉点が中心金属から離れてしまうが，生成物の光学純度と触媒活性の最適化により機能的な不斉配位子の可能が可能になり，有機合成化学に寄与できると信じている．