Asymmetric synthesis via aryne intermadiate with dynamic chirality

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06452
• 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: Kanazawa University
• Principal Investigator: YOSHIMURA Tomoyuki 金沢大学, 薬学系, 准教授 (20432320)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 不斉合成 / 軸不斉 / アライン / 環化付加反応

Outline of Final Research Achievements

Asymmetric synthesis of axially chiral biaryl compounds via a chiral aryne intermediate with dynamic chirality was developed. Treatment of the precursor of aryne intermediate and various kinds of arynophile with an alkylmetal reagent gave C2-symmetrical biaryl compounds in up to 80% yield with high preservation ratio of enantiomeric excess because rapid cycloaddition reaction occurred between the generated chiral aryne intermediated and an arynophile. It was found that the reaction proceed with retention of the configuration. Interestingly, amplification of enantiomeric excess was observed under certain reaction conditions.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

従来、反応制御が困難であったアライン中間体は新規発生方法の開発や反応条件の精査により重要な合成手法の一つとなりつつある。このアライン中間体に不斉記憶の概念を適応し、不斉誘導反応へと展開することで、多様な軸不斉ビアリール化合物の創製に繋がった。本法の開発により、今まで合成が困難であった不斉ビアリール類創製に繋がる可能性があり、有機合成化学の分野のみならず、ヘテロアリール類を多く取り扱う医薬品化学分野にも多大な貢献をもたらすと考えられる。