アリファティックアミンによる塩基感受性五合体ヘテロアリルハリドのPd触媒化アミネーション
Elaine C Reichert1, Kaibo Feng1, Aaron C Sather2
1Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
Journal of the American Chemical Society
|January 31, 2023
まとめ
新しいパラジウム触媒法により,5基のヘテロアリルハライドと様々なアミンのC-Nクロスカップリングが効率的に可能になる. この汎用的なアプローチは,ステリカルに要求される基板の課題を克服し,薬学的に重要な化合物を生み出します.
科学分野:
- 有機化学
- キャタリシス
- 薬剤化学
背景:
- パラジウム触媒によるC-Nクロスカップリングは,窒素を含む化合物の合成に不可欠です.
- 5基のヘテロアリルハライドとステリル阻害アミンの結合反応は依然として困難である.
- 既存の方法は,しばしば機能群の許容性と基板の範囲が限られている.
研究 の 目的:
- Pd触媒によるC-Nクロスカップリングのための多用途かつ機能群耐性の方法を開発する.
- 挑戦的な5つ組のヘテロアリルハライドと様々な一次および二次アミンの結合を可能にします.
- 交互結合反応におけるステリカルに要求されるアミンの未熟な変換に対処する.
主な方法:
- GPhosリガンドでサポートされたパラジウム触媒を使用した.
- 中程度の強度ベースとしてトリメチルシラノレートナトリウム (NaOTMS) を使用した.
- 結合効率に対するベースと触媒システムの相乗効果を調査した.
主要な成果:
- 2-H-1,3-アゾールのような薬学的に重要なヘテロアレンを含む結合反応で,良好から優れた収量を達成した.
- 様々な五基ヘテロアリルハライドとステリカルに要求される周期性および非周期性二次アミンの高生産性結合が初めて実証された.
- 薬剤化学の密度の高い構成要素を成功裏に結合し,広範な適用性を示しました.
結論:
- 開発された方法は,C-Nクロスカップリングのための多用途で機能グループ耐性アプローチを提供します.
- NaOTMSベースとGPhosサポートされたPd触媒の組み合わせは,触媒の無効化とステリック障害を効果的に克服します.
- この方法論は,薬物発見に関連する複雑な窒素を含むヘテロサイクルの構築のための合成ツールキットを拡張します.
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