Development of an efficient asymmetric synthetic method for chiral amines bearing a fluoroalkyl group

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06489
• 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: Institute of Physical and Chemical Research
• Principal Investigator: Kawamura Shintaro 国立研究開発法人理化学研究所, 環境資源科学研究センター, 上級研究員 (60732956)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: フルオロアルキル分子 / アミン / 銅触媒 / ラジカル反応 / DFT計算

Outline of Final Research Achievements

This research aimed at developing a novel synthetic method for chiral cyclic amines bearing a fluoroalkyl group through catalytic asymmetric reactions using alkenes as starting materials. I successfully identified a core ligand skeleton for copper catalysts capable of inducing chirality. Additionally, optimization of the reaction conditions, including the use of additives, achieved good enantioselectivity. Furthermore, through experimental and theoretical investigations, a comprehensive evaluation of the structures and reactivities of reactive intermediates, including fluorinated diacyl peroxides and fluoroalkyl radicals, provided significant insights for the further precise design of the target asymmetric reaction. I also found that the ligand influences the reaction mechanism.

Free Research Field

化学系薬学

Academic Significance and Societal Importance of the Research Achievements

光学活性な環状アミンは生理活性分子に散見され、合成化学におけるビルディングブロックとしても汎用される重要骨格である。一方、フルオロアルキル基は、主骨格分子の代謝安定性や膜透過性を向上させることが知られており、創薬研究において薬理動態の改善を目的に常套的に導入される官能基である。これらを併せ持つハイブリッド分子は新規な医薬や農薬の開発において有望であるが、その効率的な合成は未だ困難な状況にあった。本研究で得られた成果は解決の糸口となり得る。