インドリン領域選択性の逆転とインドラクタムVの合成
Sarah M Bronner1, Adam E Goetz, Neil K Garg
1Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States.
Journal of the American Chemical Society
|March 1, 2011
まとめ
研究者たちは,典型的な4,5-インドリンと比べて,反応における地域選択性を逆転させ,新しいインドリンを設計した. この方法は,代用されたインドールとインドールアルカロイドの制御された合成を可能にします.
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:
- 4,5-インドリンは通常,化学反応において予測可能な地域選択性を示す.
- 地域選択性を制御することは,複雑なインドール誘導体を合成するために極めて重要です.
研究 の 目的:
- 逆の地域選択性を持つ新しいインドリンを設計し,合成する.
- アリーヌ地域選択性を予測するための計算方法を開発する.
- C4で置換されたインドルアルカロイドのための新しい合成経路を実証する.
主な方法:
- 新型インドリン前駆物の設計と合成.
- 地域選択性を予測するために単純な計算モデルを適用する.
- 新型インドリンを用いた核性添加およびサイクル添加反応.
- コンセプトの証明としてインドラクタムVの合成.
主要な成果:
- 合成されたインドリンは,核愛添加およびサイクル添加反応において逆回転的地域選択性を示した.
- 計算による予測は,地域選択の結果を正確に導き出した.
- ベンゼノイド代用新型インドールの合成に成功し,高レジオコントロール.
- インドラクタムVを含むC4置換のインドルアルカロイドへの非常識な経路を示した.
結論:
- 新型インドリンは,インドール合成における地域選択性を制御するための強力なツールを提供します.
- 計算による予測は,非対称なアリンズで反応を設計するための信頼性の高い戦略を提供します.
- この方法論は,価値あるインドルアルカロイドへの合成アクセスを拡大します.
関連する概念動画
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.
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.
01:33Regioselective Formation of Enolates
As depicted in the figure below, the unsymmetrical ketones can form two possible enolates: less substituted or more substituted enolates. Usually, the thermodynamic enolates are formed from the more substituted α-carbon atom, while the kinetic enolates are formed faster by deprotonation from the less substituted position. The thermodynamic enolates have lower energy, so they are more stable. But the energy required to form kinetic enolates is less.
02:17Regioselectivity of Electrophilic Additions to Alkenes: Markovnikov's Rule
If a set of reactants can yield multiple constitutional isomers, but one of the isomers is obtained as the major product, the reaction is said to be regioselective. In such reactions, bond formation or breaking is favored at one reaction site over others.
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...
01:57Preparation of Diols and Pinacol Rearrangement
Compounds bearing two hydroxyl groups are known as diols. When the hydroxyl groups are located on adjacent carbon atoms, the diols are called vicinal diols or glycols. Under acidic conditions, vicinal diols undergo a specific reaction called pinacol rearrangement.
The reaction begins with transferring a proton from the acid catalyst to one of the hydroxyl groups, producing an oxonium ion.
The reaction begins with transferring a proton from the acid catalyst to one of the hydroxyl groups, producing an oxonium ion.
01:29Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry
Diels–Alder reactions between cyclic dienes locked in an s-cis configuration and dienophiles yield bridged bicyclic products.