リガンド活性化Pd (II) - 触媒化 γ-C (sp) -H 原生アミドの乳分化
Shuang Liu1, Zhe Zhuang1, Jennifer X Qiao2
1Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Journal of the American Chemical Society
|December 16, 2021
まとめ
この研究は,アミノ酸から直接 γ-ラクタムを合成するための新しいパラジウム触媒法を導入している. この効率的なアプローチは,レナリドミドの類似品のような有価な製薬構成要素への効率的な経路を提供します.
科学分野:
- 有機化学
- 薬剤化学
- カタリシス
背景:
- γ- ラクタムは,免疫調節性イミド薬 (IMiDs) とブリヴァラセタムファミリーを含む多数の医薬品における重要な構造モチーフである.
- 現在の合成方法は多くの場合 複数のステップを伴うため これらの貴重な化合物の効率とアクセシビリティを制限しています
- アミドの直接的分子内 γ-C-H アミネーションは,豊富なアミノ酸前駆体から γ-ラクタムコアを構築するための魅力的な代替案です.
研究 の 目的:
- γ-ラクタム,イソインドリノン,および2-イミダゾリドニノンの直接合成のための新しい効率的な方法を開発する.
- アミノ酸由来アミドのパラジウムによって触媒化された分子内 γ-C-sp3-H 乳分化を探求する.
- 簡単に手に入る材料を使って,実用的で環境に優しいプロトコルを確立する.
主な方法:
- 新しい2ピリドンリガンド活性化パラジウム (II) 触媒反応を用いた.
- N-アシルアミノ酸を指向グループとサイクルパートナーとして使用した.
- 反応における唯一の酸化物質として,ターチルブチル過酸化物 (TBHP) を使用した.
主要な成果:
- Pd (II) -触媒化された γ-C (sp3) -H乳化により, γ-ラクタム,イソインドリノーン,および2-イミダゾリドニノンを合成した.
- 2ピリドンのリガンドに対するC6置換が効率的なラクトーム形成に重要な役割を果たしていることが示された.
- 開発されたプロトコルの広範な基板の範囲を示した.
結論:
- 開発されたプロトコルは,アミノ酸前駆体から貴重な γ-ラクタムモチーフへの便利で直接的な経路を提供します.
- このメソッドの有用性は,レナリドミドアナログとブリバラセタムの2段階の合成によって検証された.
- このアプローチは,医薬品化学における従来の多段階合成に,実用的で,潜在的によりグリーンな代替手段を提供します.
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01:29Preparation of Amides
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