アリファティックアミンのエナチオコンバーゲントCu触媒によるN-アルキル化
Ji-Jun Chen1, Jia-Heng Fang1, Xuan-Yi Du1
1Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, China.
Nature
|March 20, 2023
まとめ
研究者たちは 薬剤や農薬に不可欠な キラルアミンを生成するための 銅を触媒とする新しい方法を開発しました この突破は,これらの貴重な化合物を 選択的に合成する以前の限界を克服しました.
科学分野:
- 有機化学
- カタリシス
- 非対称合成
背景:
- チラルアミンは 医薬品と農薬業界で不可欠な構成要素です
- アミンのための既存のN-アルキル化方法は,触媒中毒やエナチオセレクティブ性の欠如などの課題に直面しています.
- 非自然なキラルアミンを生産するための効率的な触媒的非対称的な方法に対する需要は大きい.
研究 の 目的:
- アリファティックアミンのN-アルキル化のための新しい触媒的非対称的方法を開発する.
- 原料の化学物質から非自然なキラル α-アミノアミドのエナンチオセレクティブ合成を可能にします.
- トランジションメタルのアミンアルキル化で 触媒の毒性の問題を克服するために
主な方法:
- 銅触媒でキラル三酸アニオンリガンドを使用した.
- アリファティックアミンの化学選択およびエナチオコンバージェントのN-アルキル化がα-カルボニルアルキル塩化物で用いられる.
- アンモニアや薬学的に重要なアミンのような原料化学物質にこの方法を適用した.
主要な成果:
- 単純なアミンを非自然なキラルアミノアミドに直接変換する.
- 優れた抗選択性と幅広い機能群耐性を示した.
- 薬剤の末期機能化と迅速な合成に成功しました
結論:
- チラル三酸アニオンリガンドは,移行金属触媒中毒を克服するための一般的な解決策を提供します.
- 開発された銅触媒方式は,価値あるキラルアミンへの頑丈で穏やかな経路を提供します.
- このアプローチは,複雑なキラルアミンを含む分子の合成を大幅に進める.
さらに関連する動画
08:12A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species
Published on: August 16, 2018
10.1K
10:42Preparation of N-2-alkoxyvinylsulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines
Published on: January 3, 2018
9.8K
関連する概念動画
01:22Preparation of 1° Amines: Azide Synthesis
4.1K
Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide synthesis method can be used.
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
4.1K
01:30Preparation of Amines: Alkylation of Ammonia and Amines
3.6K
Alkylation is one of the methods used to prepare amines. Direct alkylation of ammonia or a primary amine with an alkyl halide gives polyalkylated amines along with a quaternary ammonium salt through successive SN2 reactions. This process of making the quaternary salt through the direct alkylation method is called exhaustive alkylation.
Each alkylation step makes the nitrogen center more nucleophilic, which triggers successive alkylations until a quaternary ammonium salt is formed. Considering...
Each alkylation step makes the nitrogen center more nucleophilic, which triggers successive alkylations until a quaternary ammonium salt is formed. Considering...
3.6K
01:19Amines to Amides: Acylation of Amines
2.6K
Various carboxylic acid derivatives (such as acid chlorides, esters, and anhydrides) can be used for the acylation of amines to yield amides. The reaction requires two equivalents of amines. The first amine molecule functions as a nucleophile and attacks the carbonyl carbon to produce a tetrahedral intermediate. This is followed by the loss of the leaving group and restoration of the C=O bond.
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary...
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary...
2.6K
01:13Preparation of Amines: Reduction of Amides and Nitriles
2.5K
Nitriles can be reduced to primary amines using reducing agents like lithium aluminum hydride or catalytic hydrogenation. The reduction introduces an amino group with an extra carbon in the skeleton. Nitriles are formed from the reaction between alkyl halides and sodium cyanide through the SN2 mechanism. Primary alkyl halides are the preferred substrates to prepare nitriles.
Amides can be reduced to primary, secondary, and tertiary amines using catalytic hydrogenation, active metals like Fe,...
Amides can be reduced to primary, secondary, and tertiary amines using catalytic hydrogenation, active metals like Fe,...
2.5K
01:28Preparation of 1° Amines: Gabriel Synthesis
3.7K
Direct alkylation is not a suitable method for synthesizing amines because it produces polyalkylated products. Gabriel synthesis is the most preferred method to exclusively make primary amines. The method uses phthalimide, which contains a protected form of nitrogen that participates in alkylation only once to predominantly give primary amines.
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
3.7K
01:26Preparation of 1° Amines: Hofmann and Curtius Rearrangement Mechanism
3.6K
The Hofmann and Curtius rearrangement reactions can be applied to synthesize primary amines from carboxylic acid derivatives such as amides and acyl azides. In the Hofmann rearrangement, a primary amide undergoes deprotonation in the presence of a base, followed by halogenation to generate an N-haloamide. A second proton abstraction produces a stabilized anionic species, which rearranges to an isocyanate intermediate via an alkyl group migration from the carbonyl carbon to the neighboring...
3.6K