移動性ヒドロアミネーション:ベンゾモルファンの簡単なエナンチオセレクティブ合成
1Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA. bmtrost@stanford.edu
Journal of the American Chemical Society
|July 17, 2003
まとめ
私たちは,ベンゾモルファンを合成する新しい効率的な方法を開発しました. この戦略は,複雑な分子構造のための新しいサイクロアイソメリゼーションとパラジウム触媒反応を利用しています.
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:
- ベンゾモルファンは,重要な薬理学的な可能性を持つアルカロイドのクラスです.
- 既存の合成経路には,効率性やエナチオセレクティブ性が欠けていることが多い.
- 一般的で効率的なエナチオセレクティブ合成の開発は,新しいベンゾモルファン誘導体へのアクセスに不可欠です.
研究 の 目的:
- ベンゾモルファンのエナチオセレクティブ合成のための高効率で一般的な戦略を確立する.
- 複雑な分子合成における新しい合成方法の有用性を実証する.
主な方法:
- ケトンエノラートによるパラジウム触媒による非対称アリルアルキレーション (AAA) を利用したエナンチオセレクティブ合成.
- 移動性ヒドロアミネーションによる新しいダイアステロ選択性サイクロアイソメリゼーション.
- 商業的に利用可能な原材料から得られた45~46%の総収量.
主要な成果:
- ベンゾモルファンのエナチオセレクティブ合成が成功し,総産量が高い.
- 前例のないダイアステロセレクティブサイクロイソメリゼーション反応の実証.
- パラジウムで触媒化されたAAAを複合合成で効果的に適用し,3つの連続したステレオゲンなセンターを確立します.
結論:
- 開発された戦略は,エナチオセレクティブベンゾモルファン合成のための強力で一般的なアプローチを提供します.
- 新型サイクロイソメリゼーションとAAAの方法論は,アルカロイド合成において広く適用可能である.
- この研究は,ベンゾモルファンベースの新しい治療法の発見のための基盤を提供します.
関連する概念動画
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Overview
The acid-catalyzed addition of water to the double bond of alkenes is a large-scale industrial method used to synthesize low-molecular-weight alcohols. An acidic atmosphere is required to allow the hydrogen in the water molecule to act as an electrophile and attack the double bond in an alkene. The addition of a proton to the double bond creates a carbocation intermediate. The proton preferentially bonds to the less substituted end of the double bond to create a more stable carbocation...
The acid-catalyzed addition of water to the double bond of alkenes is a large-scale industrial method used to synthesize low-molecular-weight alcohols. An acidic atmosphere is required to allow the hydrogen in the water molecule to act as an electrophile and attack the double bond in an alkene. The addition of a proton to the double bond creates a carbocation intermediate. The proton preferentially bonds to the less substituted end of the double bond to create a more stable carbocation...
02:35Acid-Catalyzed Dehydration of Alcohols to Alkenes
In a dehydration reaction, a hydroxyl group in an alcohol is eliminated along with the hydrogen from an adjacent carbon. Here, the products are an alkene and a molecule of water. Dehydration of alcohols is generally achieved by heating in the presence of an acid catalyst. While the dehydration of primary alcohols requires high temperatures and acid concentrations, secondary and tertiary alcohols can lose a water molecule under relatively mild conditions.
01:01Acid Halides to Carboxylic Acids: Hydrolysis
Hydrolysis of acid halides is a nucleophilic acyl substitution reaction in which acid halides react with water to give carboxylic acids. The reaction occurs readily and does not require acid or a base catalyst.
As shown below, the mechanism involves a nucleophilic attack by water at the carbonyl carbon to form a tetrahedral intermediate. This is followed by the reformation of the carbon–oxygen π bond along with the departure of a halide ion. A final proton transfer step yields carboxylic acid...
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01:21Acid-Catalyzed α-Halogenation of Aldehydes and Ketones
By replacing an α-hydrogen with a halogen, acid-catalyzed α-halogenation of aldehydes or ketones yields a monohalogenated product
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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...