Development of regioselective sp3 C-H functionalization catalyst with substrate recognition site

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06545
• 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: The University of Tokyo
• Principal Investigator: Oisaki Kounosuke 東京大学, 大学院薬学系研究科(薬学部), 講師 (00583999)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: C-H活性化 / 有機ラジカル / フォトレドックス触媒 / 水素原子移動触媒 / 結合弱化触媒

Outline of Final Research Achievements

We have been working on the development of catalysts that enable catalytic control of site-selectivity, which is an unsolved problem in catalytic C(sp3)-H transformation.
(1) By designing HAT catalysts with alcohol recognition moiety, we attempted to achieve site-selective C(sp3)-H transformations through a pseudo-intramolecular transition state. However, this approach was abandoned in the face of various problems.
(2) We conducted DFT-guided screening of bond-weakening catalysts that could lower the bond dissociation energy (BDE) by recognizing alcohol moiety, and found silicate or borate species to be candidates. Based on this finding, we developed a cooperative catalytic system promoting alcohol alpha-C-H alkylations using Martin spirosilane and electron-deficient boric acid as the embodiment of bond-weakening catalyst.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

最終生成物に頻度高く含まれる官能基（ヒドロキシル基やカルボニル基など）を足がかりとし、各々のC-H結合を区別したうえで位置選択的な変換可能な触媒を開発できれば、物質機能を担保したうえでの構造展開を可能とするLate-Stage誘導体化法の拡充や、複雑化合物の合成短工程化にも寄与し、機能性物質創製プロセスを加速させるような方法論となることが期待される。本研究にて開発に成功した結合弱化触媒系は、現在世界中の研究者が取り組んでいるC(sp3)-H変換触媒開発とその位置選択性制御という重要課題に対し、解決をもたらしうる全く新たな角度からの触媒設計指針を提供する。