非対称な有機触媒三成分1,3-二極サイクロアディション:キラルブレンステッド酸活性化ディポールによるステレオ化学の制御
Xiao-Hua Chen1, Wen-Quan Zhang, Liu-Zhu Gong
1Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei 230026, China.
Journal of the American Chemical Society
|April 5, 2008
まとめ
新しいビスホスフォリ酸が3つの成分反応を触媒化し,高いエナチオセレクティブ性を持つ代用ピロリジンを効率的に生成します. この方法は,複雑なキラル分子を合成するための穏やかで効果的な経路を提供します.
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
- 合成方法論 合成方法論
背景:
- 三要素反応は,複雑な分子に効率的な合成経路を提供します.
- 非対称な触媒は,エナティオメリカルに純粋な化合物を生成するために極めて重要です.
- ピロリジン・スキャフォールドは,医薬品や天然製品に多く見られます.
研究 の 目的:
- 非対称な3つの成分反応のための新しいブロンステッド酸触媒を開発する.
- 高いエナチオ選択性を持つ複数の置換ピロリジンを合成する.
- この変換のための穏やかな反応条件を確立するために.
主な方法:
- 結合されたBINOLから派生した新しいビスホスフォリック酸を触媒として使用した.
- アルデヒド,アミノエステル,および二極性分子を含む3つの成分反応を採用しました.
- 温度,溶媒,触媒の負荷を含む反応パラメータを最適化しました.
主要な成果:
- 複数の代用ピロリジンの高収量を達成した.
- 製品に対する優れたエナチオセレクティブ性 (高いee値) を実証した.
- 反応は穏やかな条件下でも効率的に進行した.
結論:
- 開発されたビスホスフォリ酸は,非対称的1,3-二極サイクロアディションの効果的な触媒である.
- この方法論は,価値あるピロリジン誘導体への簡単で選択的でないアクセスを提供します.
- 温和な条件により,このアプローチはより広範な合成用途に魅力的です.
関連する概念動画
01:25Radical Anti-Markovnikov Addition to Alkenes: Overview
The addition of hydrogen bromide to alkenes in the presence of hydroperoxides or peroxides proceeds via an anti-Markovnikov pathway and yields alkyl bromides.
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.
01:28Diels–Alder Reaction Forming Cyclic Products: Stereochemistry
The Diels–Alder reaction is one of the robust methods for synthesizing unsaturated six-membered rings. The reaction involves a concerted cyclic movement of six π electrons: four π electrons from the diene and two π electrons from the dienophile.
02:05Prochirality
The concept of prochirality leads to the nomenclature of the individual faces of a molecule and plays a crucial role in the enantioselective reaction. It is a concept where two or more achiral molecules react to produce chiral products. A typical process is the reaction of an achiral ketone to generate a chiral alcohol. Here, the achiral reactant reacts with an achiral reducing agent, sodium borohydride, to generate an equimolar mixture of the chiral enantiomers of the product. For example, an...
02:35Regioselectivity of Electrophilic Additions-Peroxide Effect
In the presence of organic peroxides, the addition of hydrogen bromide to an alkene yields the isomer that is not predicted by Markovnikov’s rule. For example, the addition of hydrogen bromide to 2-methylpropene in the presence of peroxides gives 1-bromo-2-methylpropane. This addition reaction proceeds via a free radical mechanism, which reverses the regioselectivity. The free radical reaction mechanism involves three stages: initiation, propagation, and termination.
02:34Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration
The rate of acid-catalyzed hydration of alkenes depends on the alkene's structure, as the presence of alkyl substituents at the double bond can significantly influence the rate.