Development of innovative one-pot multi-step continuous cross-coupling reaction by dynamic control of catalyst structure

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21469
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: Tohoku University
• Principal Investigator: Tokuyama Hidetoshi 東北大学, 薬学研究科, 教授 (00282608)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: 連続反応 / クロスカップリング / 遷移金属触媒 / 亜鉛試薬 / ケトン

Outline of Final Research Achievements

Based on our previously developed ketone synthesis by Pd-catalyzed coupling reaction of thioesters and organozinc reagents, we have investigated a novel unsymmetrical ketone synthesis by employing a ligand controlled, Pd-catalyzed one-pot sequential coupling reaction between a dithiocarbonate and two different organozinc reagents. Extensive investigation allowed to develop asymmetrical synthesis of aryl and heteroaryl ketones. A short-step total synthesis of marine tricyclic alkaroid (+)-cylindricine C was achieved by employing the double coupling reaction using highly functionalized organozinc reagents. The total synthesis was then achieved via an acid catalyzed cascade cyclization reaction. In addition, we have developed a novel multicomponent asymmetric 1,3-diketone synthesis.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

本反応は、類似の報告がなく学術的に独創性が高い。また、配位子による触媒の動的制御は他の反応へも応用可能であり、新規連続反応の開発につながることが期待される。さらに、本反応により、中分子領域の高次構造天然物と幅広い誘導体の収束的かつ網羅的な合成供給につながり、医薬資源のマイニング、高次構造天然物、誘導体の迅速合成を基にしたライブラリー構築と構造活性相関研究、また、高次構造天然物をモチーフとする分子プローブの開発を利用した作用機序の解明など、創薬研究に与える波及効果は極めて大きい。