ステレオ選択的水素アミネーション変換により,ポリ置換されたインドリジジジンにアクセスできます
Sergey V Pronin1, M Greg Tabor, Daniel J Jansen
1Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Journal of the American Chemical Society
|January 24, 2012
まとめ
新しいステレオセレクティブ・ヒドロアミネーション法により,インドリジジンアルカロイドの合成が可能です. このプロセスは,単純な不飽和アミンから4つのステレオセンターを効率的に生成し,自然および非自然の両方の化合物を生成します.
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
- 薬用化学 薬用化学について
背景:
- インドリジジンアルカロイドは,多様な生物学的活動を持つ重要な種類の天然製品です.
- これらの複雑な分子への効率的でステレオ選択的な合成経路は,非常に求められています.
研究 の 目的:
- インドリジジンアルカロイドの合成のための新しいステレオ選択的方法の開発.
- ディエンアミンに適用可能な公式の水素アミナ反応を確立するために.
主な方法:
- この研究では,デアミンのステレオ選択的,分子内,形式的な水素アミナ化が報告されています.
- この反応は,指向された水酸化メカニズムによって進行します.
- このプロセスは,1つの変換で4つのステレオセンターを効果的に設定します.
主要な成果:
- 開発された方法は,複雑な分子構造の構築を可能にします.
- 4つのステレオセンターは,反応中に正確に制御されます.
- 単純な不飽和アミンから天然および非天然のインドリジジンアルカロイドの両方の合成が実証されています.
結論:
- この研究は,インドリジジジンアルカロイドにアクセスするための強力な新しい戦略を提示しています.
- 誘導的水酸化媒介による水酸化アミネーションは,貴重な化学的支架への効率的な経路を提供します.
- この方法論は,さらなる生物学的評価のために多様なアルカロイド誘導体の合成に有望である.
関連する概念動画
01:19Diazonium Group Substitution: –OH and –H
Nitrous acid, a weak acid, is prepared in situ via the reaction of sodium nitrite with a strong acid under cold conditions. This nitrous acid prepared in situ reacts with primary arylamines to form arenediazonium salts. Such reactions are known as diazotization reactions. As shown in Figure 1, the formation of arenediazonium salts begins with the decomposition of nitrous acid in an acidic solution to give nitrosonium ions.
02:36Regioselectivity and Stereochemistry of Hydroboration
A significant aspect of hydroboration–oxidation is the regio- and stereochemical outcome of the reaction.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
01:22Preparation of 1° Amines: Azide Synthesis
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...
01:20Diazonium Group Substitution with Halogens and Cyanide: Sandmeyer and Schiemann Reactions
Arenediazonium substitution reactions occur when the diazonium group is substituted by various functional groups such as halides, hydroxyl, nitrile, etc. For instance, arenediazonium salts react with copper(I) salts of chloride, bromide, or cyanide to form corresponding aryl chlorides, bromides, and nitriles. These reactions are named Sandmeyer reactions. Although the mechanism of this reaction is complicated, as illustrated in Figure 1, they are believed to progress via an aryl copper...
02:47Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation
Introduction
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
02:23SN2 Reaction: Stereochemistry
In an SN2 reaction, the nucleophilic attack on the substrate and departure of the leaving group occurs simultaneously through a transition state. As the nucleophile approaches the substrate from the back-side, the configuration of the substrate carbon changes from tetrahedral to trigonal bipyramidal and then back to tetrahedral, leading to an inversion in the configuration of the product.
If the substrate is an achiral molecule at the α-carbon, the inversion of configuration is not observed.
If the substrate is an achiral molecule at the α-carbon, the inversion of configuration is not observed.