クロスカップリングのためのメチル化剤としてのトリメチルホスファート:アリルボロンエステルのメチル化のための緩解メカニズム

Zhi-Tao He¹, Haoquan Li¹, Alexander M Haydl¹

¹Department of Chemistry , University of California , Berkeley , California 94720 , United States.

Journal of the American Chemical Society

|November 14, 2018

まとめ

この研究では,軽度で無毒な反応剤であるトリメチルフォスファートを用いた新しい銅触媒メチル化法が導入されています. この効率的なプロセスは,薬用化合物における惰性C−H結合の機能化を可能にします.

科学分野:

有機化学
カタリシス
薬剤化学

背景:

メチル群は分子の生物学的活動に大きく影響する.
伝統的なメチル化方法は,しばしば厳しいまたは有毒な反応剤を使用します.
より穏やかで安全で効率的なメチル化戦略が必要である.

研究の目的:

アリルおよびヘテロアリルボロンエステルの高効率のメチル化を開発する.
トリメチルファスファートを軽度で無毒なメチル化剤として結合反応で使用する.
慣性C−H結合の機能化のための新しいアプローチを確立する.

主な方法:

トリメチルフォスファートを用いてアリルおよびヘテロアリルボロンエステルの銅とヨウ素の共催化メチル化.
C-H ボリル化とメチル化の組み合わせ
信頼性を証明するために200mmolのスケールアップ反応.
トリメチルフォスファートとヨウ素触媒を含むメカニズム研究.

主要な成果:

アリル・エステルとヘテロアリルボロンエステルをトリメチルフォスファートでメチル化することで高い収量が得られる.
MeOTsやMeIのような伝統的なメチル化剤と比較して優れていると証明されています.
4つの薬効性化合物の末期メチル化に成功しました
メカニズムの研究により,トリメチルフォスファートからメチルヨウ素の緩やかな放出が明らかになった.

結論:

開発された方法は,メチラレン合成のための新しい,効率的で穏やかな戦略を提供します.
C-Hボリレーションとトリメチルフォスファートメチレーションの組み合わせは,惰性C-H結合の機能化のための多用途な経路を提供します.
反応の信頼性と軽度の条件は,薬学化学の遅い段階の機能化に適しています.

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