アミジンベースの触媒を用いたラクタムとチオラクトムの触媒的,エナチオセレクティブのN-アサイル化
Xing Yang1, Valentina D Bumbu, Peng Liu
1Department of Chemistry, Washington University, One Brookings Drive, St. Louis, Missouri 63130, USA.
Journal of the American Chemical Society
|October 4, 2012
まとめ
ラセミックなラクタムとチオラクタムは,アミジン触媒による非対称なN-アシレーションを用いて解消することができる. この方法は,これらの化合物の伝統的な解像技術の限界を克服し,高いエナンチオセレクティブ性を提供します.
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:
- ラセミア系ラクタムとチオラクタムは,酵素アシレーションや古典的解像度などの従来の方法を使用して解消することは困難です.
- アルコールとアミンは,ラクタムとチオラクタムとは異なり,既定の技術によってより容易に分解できます.
研究 の 目的:
- ラセミカルラクタムとチオラクタムの運動分解のための便利で効果的な方法を開発する.
- これらの貴重な化合物の分解プロセスで高いエナチオセレクティビティを達成するために.
主な方法:
- Cl-PIQ 2 や BTM 3 などのアミジンベースの触媒を用いて,非対称な N-アシレーション反応が採用されました.
- 反応機構とキラル認識の側面を明らかにするために,密度関数理論 (DFT) の計算を行いました.
主要な成果:
- アミジンベースの触媒,特にCl-PIQ 2とBTM 3は,ラクタムとチオラクタムの運動分解に有効性を示しました.
- 非対称なN-アシレーションプロセスでは,しばしば優れたレベルのエナチオセレクティビティが達成されました.
- DFTの計算により,この反応は乳酸タウトメアのN-アシラ化によって進行することが確認された.
- カチオン-π相互作用は,触媒過程中のラクタム基板のキラル認識に不可欠であると特定されました.
結論:
- アミジン誘導体によって触媒化された非対称なN-アシレーションは,ラセミックラクタムとチオラクタムを分解するための実行可能で効率的な戦略を提供します.
- 乳酸タウトメアアシレーションとカチオン-π相互作用を含む反応機構の理解は,キラル認識のためのより効果的な触媒の設計に役立ちます.
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関連する概念動画
01:19Amines to Amides: Acylation of Amines
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 amide...
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary amide...
01:13Preparation of Amines: Reduction of Amides and Nitriles
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,...
01:07Acid Halides to Amides: Aminolysis
Aminolysis is a nucleophilic acyl substitution reaction, where ammonia or amines act as nucleophiles to give the substitution product. Acid halides react with ammonia, primary amines, and secondary amines to yield primary, secondary, and tertiary amides, respectively.
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
01:20Amides to Amines: LiAlH4 Reduction
Amide reduction with strong reducing agents like lithium aluminum hydride proceeds through a nucleophilic acyl substitution to form amines. Primary, secondary, and tertiary amides yield primary, secondary, and tertiary amines, respectively.
Amide reduction requires two equivalents of the reducing agent, acting as a source of hydride ions. As shown in the figure, the reaction is initiated with a nucleophilic attack by the hydride ion at the carbonyl carbon to form a tetrahedral intermediate.
Amide reduction requires two equivalents of the reducing agent, acting as a source of hydride ions. As shown in the figure, the reaction is initiated with a nucleophilic attack by the hydride ion at the carbonyl carbon to form a tetrahedral intermediate.
01:29Preparation of Amides
Amides are synthesized by treating carboxylic acids with amines in the presence of dehydrating agents like dicyclohexylcarbodiimide (DCC).
The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
Subsequently, the amine acts as a nucleophile that attacks the acylating agent to form a tetrahedral intermediate. In the...
The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
Subsequently, the amine acts as a nucleophile that attacks the acylating agent to form a tetrahedral intermediate. In the...
01:26Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction
α-Substituted ketones or aldehydes can be synthesized from enamines by the Stork enamine reaction, named after its pioneer Gilbert Stork. Enamines are useful synthetic intermediates where the lone pair on nitrogen is in conjugation with the C=C bond. They resemble enolate ions, as the resonance forms of both species have a nucleophilic α carbon.