ダイナミック・キネティック解像度によるエナンチオセレクティブ・ニッケル・カタライズド・アルキネ・アジド・サイクロアディション
En-Chih Liu1, Joseph J Topczewski1
1Department of Chemistry, University of Minnesota Twin Cities, Minneapolis, Minnesota 55455, United States.
Journal of the American Chemical Society
|April 2, 2021
まとめ
研究者はニッケル触媒アルキネアジドサイクル添加 (NiAAC) を使用して,キラルトリアゾールの最初のエナント選択合成を開発した. この方法は,既存の銅触媒反応を補完して,価値あるキラル構成要素への新しい経路を提供します.
科学分野:
- 有機化学
- 薬剤化学
- カタリシス
背景:
- トリアゾールヘテロサイクルは,医薬品化学におけるアミド結合の一般的なイソステルである.
- 多くの生物学的に重要なアミドは,アミノ酸から生じるキラルである.
- 薬の発見と開発にはキラルトリアゾールのビルディングブロックの開発が不可欠です.
研究 の 目的:
- 1,4,5-トリサゾールの最初のエナンチオセレクティブ合成を報告する.
- 非対称合成の方法として,ニッケル触媒アルキネアジドサイクル添加 (NiAAC) を確立する.
- トリアゾール形成のための新しい動的運動解像度経路を探求する.
主な方法:
- ニッケル触媒によるアルキンアジドサイクル添加 (NiAAC) 反応
- アリルアジドの自発的な[3,3]-シグマトロピク再配置を用いて,動的運動解像度を得る.
- 内部アルキンを利用して1,4,5-トリサゾール製品を生成する.
主要な成果:
- トリアゾール合成のための最初のエナンチオセレクティブの NiAAC反応を達成しました.
- 動的運動解像度によるα-N-キラルトリアゾールの形成が示された.
- NiAAC製品は,通常,銅で触媒化されたアジド-アルキンサイクル添加 (CuAAC) によって得られるものを補完します.
結論:
- Enantioselective NiAACは,キラルトリアゾールを合成するための新しい効率的な方法を提供します.
- 反応メカニズムは,CuAAC経路とは異なる単金属ニッケル複合体を含んでいる可能性が高い.
- この研究は,潜在的医薬品用キラルヘテロサイクルの化合物へのアクセスのための合成ツールボックスを拡張します.
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