酸化C-N結合形成による (+) -リコナジンAおよび関連化合物の総合成
Scott P West1, Alakesh Bisai, Andrew D Lim
1Department of Chemistry, University of California, Berkeley, California 94720, USA.
Journal of the American Chemical Society
|July 14, 2009
まとめ
研究者は,新しい酸化炭素-窒素結合形成反応を開発しました. この効率的な方法は,複合性アルカロイドライコナジンAのエナンチオセレクティブ全合成に適用されました.
科学分野:
- 有機化学 オーガニック・ケミストリー
- 合成化学 合成化学とは
- 自然製品合成 自然製品合成
背景:
- 炭素-窒素 (C-N) 結合の形成は,有機合成において極めて重要です.
- C-N結合の構築は,アルカロイド天然製品の合成に不可欠です.
- ライコポディアム (Lycopodium) のアルカロイドであるライコナジンAは,その複雑な構造により,重要な合成課題を提示しています.
研究 の 目的:
- 高効率の酸化C-N結合形成反応を発見し,開発すること.
- この新しい反応をリコナジンAのエナンチオセレクティブ・トータル合成に適用するには,
- 新しく開発されたC-N結合形成プロセスのメカニズムを調査する.
主な方法:
- 窒素と炭素アニオンを含む新しい酸化C-N結合形成反応の開発.
- リコナジンAのエナンチオセレクティブ・トータル合成における反応の適用.
- 極性および急性プロセスの関与を解明するためのメカニズム研究.
主要な成果:
- 高効率の酸化C-N結合形成反応が発見された.
- この反応は,ライコナジンAの全合成にうまく適用されました.
- 証拠によると,反応メカニズムは極性経路と急性経路の両方を含む.
結論:
- 開発された酸化C-N結合形成は,有機合成の強力なツールです.
- この方法は,リコナジンAのような複雑なアルカロイドの効率的なエナチオセレクティブ総合成を可能にします.
- 機械的洞察は,C-Nボンド形成戦略のさらなる開発のための基盤を提供します.
関連する概念動画
01:32Aldehydes and Ketones with HCN: Cyanohydrin Formation Overview
Cyanohydrins are compounds that contain –CN and –OH groups on the same carbon atom. They are formed by the nucleophilic addition of the cyanide ions to the carbonyl group. Cyanide ions are highly basic and nucleophilic and can be generated from HCN under aqueous conditions. However, since HCN is a weak acid, the number of cyanide ions generated is very small. Hence, a small amount of base or KCN/NaCN is added to HCN to increase the concentration of the cyanide ions in the reaction mixture.
01:10Aldehydes and Ketones with HCN: Cyanohydrin Formation Mechanism
Cyanohydrins are formed when cyanide nucleophiles and carbonyl compounds like aldehydes and ketones react. A strong base, the cyanide ion, catalyzes cyanohydrin formation. The ions are generated from HCN under aqueous conditions. Once the cyanide ions are generated, the first step involves the nucleophilic attack of the cyanide ions on the electrophilic carbonyl carbon. This attack shifts the π electrons from the C=O to the oxygen atom forming the alkoxide ion intermediate. The alkoxide anion...
02:04Oxidation of Alkenes: Anti Dihydroxylation with Peroxy Acids
Diols are compounds with two hydroxyl groups. In addition to syn dihydroxylation, diols can also be synthesized through the process of anti dihydroxylation. The process involves treating an alkene with a peroxycarboxylic acid to form an epoxide. Epoxides are highly strained three-membered rings with oxygen and two carbons occupying the corners of an equilateral triangle. This step is followed by ring-opening of the epoxide in the presence of an aqueous acid to give a trans diol.
02:44Oxidation of Alkenes: Syn Dihydroxylation with Osmium Tetraoxide
Alkenes are converted to 1,2-diols or glycols through a process called dihydroxylation. It involves the addition of two hydroxyl groups across the double bond with two different stereochemical approaches, namely anti and syn. Dihydroxylation using osmium tetroxide progresses with syn stereochemistry.
01:09Conjugate Addition to α,β-Unsaturated Carbonyl Compounds
α,β-Unsaturated carbonyl compounds are molecules bearing a carbonyl and alkene functionality in conjugation with each other. The conjugation in the molecule leads to three resonance structures. The hybrid form exhibits two probable electrophilic sites: the carbonyl carbon and the β carbon.
01:27Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
Robinson annulation is a base-catalyzed reaction for the synthesis of 2-cyclohexenone derivatives from 1,3-dicarbonyl donors (such as cyclic diketones, β-ketoesters, or β-diketones) and α,β-unsaturated carbonyl acceptors. Named after Sir Robert Robinson, who discovered it, this reaction yields a six-membered ring with three new C–C bonds (two σ bonds and one π bond).