オーガノカタリティックで高度にステレオセレクティブの直接ビニールロゴスマニッヒ反応によるマニッヒ反応
Tian-Yu Liu1, Hai-Lei Cui, Jun Long
1Key Laboratory of Drug-Targeting of Education Ministry and Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Journal of the American Chemical Society
|February 1, 2007
まとめ
キラル有機触媒を用いた新しい非対称的なヴィニロログマニッヒ反応は,貴重なデルタアミノ酸の効率的な合成を可能にします. この方法は,室温で高い選択性と幅広い基板範囲を提供します.
科学分野:
- 有機化学 オーガニック・ケミストリー
- アシンメトリック・カタリシス
背景:
- マニッヒ反応は,有機合成における基本的な炭素-炭素結合形成反応である.
- 非対称な変種の開発は,エナティオメリカルに純粋な化合物にアクセスするために重要です.
- 直接的非対称ヴィニロゲスのマニッヒ反応は,特にアルファ,アルファ-ディシアノオレフィンなどの難しい基板では,あまり研究されていない.
研究 の 目的:
- アルファ,アルファ-ディシアノオレフィン,N-ボックアルジミンによる最初の直接非対称ヴィニロマニッヒ反応 (AVM) を開発する.
- この変換のための効率的で選択的な有機触媒を特定する.
- エナティオメリックに純粋なデルタアミノ酸を合成するためのアドクトの有用性を実証する.
主な方法:
- キラル双機能チオウレア三次アミン有機触媒を用いた.
- アルファ,アルファ-ディシアノオレフィンとN-Bocアルジミンの間の反応を行った.
- 触媒の負荷,温度,溶媒を含む反応条件の最適化.
- チラル高性能液体染色学 (HPLC) を使用して分析された製品の立体化学.
主要な成果:
- アルファ,アルファ-ディシアノオレフィンとN-ボックアルジミンによる最初の直接の非対称ヴィニロゲースのマニッヒ反応を達成した.
- 反応は高効率で進行した (基板と触媒の比率は1000まで).
- 優れた地域およびステレオ選択性 (一般的に99%以上のダイアステロエーマー過剰および96~99.5%以上のエナティオメール過剰) を示した.
- この反応は,室温で,幅広い基板で効果的であった.
- エナティオメリックに純粋なデルタアミノ酸は,反応添加物からスムーズに作製された.
結論:
- 新しく高度に効率的な直接非対称ビニール型マニッヒ反応が確立されました.
- 単純なキラル双機能チオウレア三次アミンの有機触媒は,この変換に有効です.
- この方法論は,薬剤化学における貴重な構成要素である,エナチオメリックに濃縮されたデルタアミノ酸への簡単な経路を提供します.
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