潜在エノラートとしてのα-ハロアミド:直接触媒非対称マンニッヒ型反応
Bo Sun1, Pandur Venkatesan Balaji1, Naoya Kumagai1
1Institute of Microbial Chemistry (BIKAKEN), Tokyo , 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.
Journal of the American Chemical Society
|May 23, 2017
まとめ
この研究は,α-ハロ7-アザインドリンアミドを用いた新しい触媒的非対称マニッヒ型反応を導入する. この方法は脱ハロゲン化問題を克服し,エンアンチオ濃縮ハロゲン化化合物の高度にステレオ選択的なC-C結合形成を可能にします.
科学分野:
- 有機化学
- 非対称な触媒
- 合成方法論
背景:
- α-ハロゲン化カルボニル化合物は,典型的には不安定で,脱ハロゲン化傾向があり,エノラート前駆体としての使用を制限しています.
- α-ハロカルボニル化合物による触媒的エナンチオセレクティブC-C結合形成反応の開発は,有機合成における重要な課題である.
研究 の 目的:
- α-ハロ7-アザインドリンアミドを用いた直接触媒非対称マニッヒ型反応の開発.
- α-ハロカルボニル化合物に関連した固有の不安定性と脱ハロゲン化問題を克服するために.
- ステレオ選択的C−C結合形成によるエナチオ濃縮ハロゲン化物の合成を調査する.
主な方法:
- α-C-ハロゲン結合の安定性を高めるために設計されたアミド戦略が使用された.
- α-ハロ7アザインドリンアミドに直接エノライゼーションの方法が適用された.
- N-カルバモイルイミンとの触媒非対称マニッヒ型反応は,様々なα-ハロ置換剤 (F,Cl,Br,I) を使用して実施された.
主要な成果:
- 反応は,すべてのα-ハロ置換物 (F,Cl,Br,I) を脱ハロゲン化なしにうまく耐えた.
- 非常にステレオ選択的なマンニッヒ・アダクトが得られた.
- アロマティックイミンの置換パターンに基づいてダイアステレオ選択性が変化することが観察され,これはオープントランジション状態モデルによって説明される.
- マニッヒ・アドゥクトの機能的グループ相互変換は,合成的有用性を示した.
結論:
- α-ハロ7-アザインドリンアミドに対する強固で汎用性の高い触媒非対称マニッヒ型反応が確立された.
- このプロトコルは,以前の制限を克服し,エナチオ濃縮ハロゲン化合物へのアクセスを提供します.
- この発見は,高度なステレオ制御を持つ複雑なハロゲン化分子を構築するための貴重な合成ツールを提供します.
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