エナチオセレクティブのチオウレア触媒による分子内コペ型ヒドロアミナーション
Adam R Brown1, Christopher Uyeda, Carolyn A Brotherton
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, United States.
Journal of the American Chemical Society
|April 20, 2013
まとめ
チラルチオウレア触媒は,ヒドロキシラミンのコペ型再配列を可能にします. この反応により,エナチオンの濃縮されたピロリジンが効率的に生成され,貴重な化合物を合成するための金属のない代替品が提供されます.
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
- 合成方法論 合成方法論
背景:
- コップ型再配列は,有機合成における貴重な変換である.
- 酵素濃縮ピロリジンへのアクセスは,医薬品開発において極めて重要です.
- 金属触媒による水素アミネーション反応は一般的ですが,制限があります.
研究 の 目的:
- Cope型の再配置のための新しい触媒システムを開発する.
- α置換ピロリジンの合成において高いエナンチオセレクティビティを達成するために.
- 既存の合成方法に対する金属のない代替手段を確立する.
主な方法:
- オーガノカタリストとしてキラルチオウレア誘導体を利用した.
- ビスホモアリルヒドロキシアミンのコップ型再配列を調査した.
- 立体化学を制御するために非対称な触媒を用いた.
主要な成果:
- ビスホモアリルヒドロキシラミンのコップ型再配列を成功的に触媒化しました.
- 高度にエンチオイン濃縮されたα置換ピロリジン製品.
- この変換におけるキラルチオウレア触媒の有効性を実証した.
結論:
- チラルチオウレア誘導体は,コペ型再配列を効果的に触媒化する.
- この方法は,エナチオンの濃縮ピロリジンへの新しい経路を提供します.
- この反応は,非対称合成における貴重な金属フリーアプローチを表しています.
関連する概念動画
01:14Amines to Alkenes: Cope Elimination
Cope elimination reaction involves the conversion of tertiary amines to alkene using hydrogen peroxide under thermal conditions, as depicted in figure 1.
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.
![[3,3] Sigmatropic Rearrangement of 1,5-Dienes: Cope Rearrangement](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2Ffiles%2Fmedia%2Fscience-education%2Fscience-education-thumbs%2F12422.jpg&w=3840&q=75)
01:21[3,3] Sigmatropic Rearrangement of 1,5-Dienes: Cope Rearrangement
The Cope rearrangement is classified as a [3,3] sigmatropic shift in 1,5-dienes, leading to a more stable, isomeric 1,5-diene. The reaction involves a concerted movement of six electrons, four from two π bonds and two from a σ bond, via an energetically favorable chair-like transition state.
01:26Preparation of 1° Amines: Hofmann and Curtius Rearrangement Mechanism
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...
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.
01:16Amines to Alkenes: Hofmann Elimination
Alkenes can be obtained from amines via an E2 elimination. The amine is first converted into a good leaving group, such as a quaternary ammonium salt. This is accomplished by treating the amine with an excess of alkyl halide, which results in a halide salt. Next, the halide salt is transformed into a hydroxide salt that functions as a base to enable elimination.
Under thermal conditions, the hydroxide can abstract a proton from the β carbon; this generates an alkene with the simultaneous...
Under thermal conditions, the hydroxide can abstract a proton from the β carbon; this generates an alkene with the simultaneous...