Immobilization of chiral cationic metal catalysts via non-covalent interactions for continuous-flow reactions

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K15557
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 33020:Synthetic organic chemistry-related
• Research Institution: The University of Tokyo
• Principal Investigator: Saito Yuki 東京大学, 大学院理学系研究科(理学部), 特任助教 (70835298)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 連続フロー / 不斉反応 / 不均一系触媒 / 水素化反応 / Friedel-Crafts反応 / ロジウム / スカンジウム

Outline of Final Research Achievements

Continuous-flow reactions with heterogeneous chiral catalysts is one of the most efficient method to synthesize optically active compounds. Conventional immobilization methods mainly rely on covalent immobilization of chiral ligands. However, these catalysts often suffer from low activity, selectivity and poor robustness. To overcome these problems, novel immobilization method using non-covalent interactions were developed. Chiral cationic complexes can be easily immobilized simply by mixing designed support in solution. Prepared heterogeneous Rh catalysts demonstrated excellent activity and enantioselectivity for hydrogenation of enamides under continuous-flow conditions. Furthermore, this immobilization method could be applicable for chiral Sc complexes, and continuous-flow enantioselective Friedel-Crafts reaction was developed.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

医薬品等の化成品の多くは光学活性化合物であるため、その連続合成は環境調和型生産の実現のための重要な手法である。不均一系触媒による連続フロー合成は触媒と生成物の分離・触媒の回収・再使用が同時に達成される有力な手法であるが、これまでの不均一系触媒は活性・選択性・耐久性に課題を有していた。本研究では非共有結合的相互作用を活用する触媒の新規固定化法の開発を行った。調整された不均一系ロジウム触媒は、水素化反応において高活性・高選択性・高耐久性を発揮し、実際の医薬有効生物の中間体の連続生産も実現した。