チオールの高度な化学選択性と実用的なアルキニル化です
1Laboratory of Catalysis and Organic Synthesis, Ecole Polytechnique Fédérale de Lausanne, EPFL SB ISIC LCSO, BCH 4306, 1015 Lausanne, Switzerland.
Journal of the American Chemical Society
|June 20, 2013
まとめ
新しいチオル-アルキニレーション法では,超有価ヨウ素反応剤を用いて,室温の反応を迅速に行う. この多用途で化学選択的なプロセスは,様々なチオルを効率的にアルキニル化し,フッ素ホルモンのラベルなど,合成後の改変を可能にします.
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
背景:
- チオルの機能化は,有機合成と生物結合において極めて重要です.
- チオールアルキニレーションの既存の方法は,反応条件,範囲,または機能群の耐性によって制限されることがあります.
研究 の 目的:
- 新しく,効率的で,広く適用可能なチオール-アルキニレーション反応の開発.
- 合成後の改変におけるこの方法の有用性を実証する.
主な方法:
- 超有価なヨウ素アルキーン移転反応剤であるTIPS-エチニルベンジオドコソロンを使用した.
- 温和な条件で反応を行った:室温,開いたフラスコ,短い反応時間 (5分).
- 拡張性のために,商業的に利用可能な反応剤を使用した.
主要な成果:
- フェノール,ベンジル,ヘテロサイクリック,アリファティックを含む様々なチオールのアルキニル化に優れた収量を達成しました.
- 高い化学選択性を示し,幅広い機能群を許容しています.
- システインを含むペプチドにポスト合成フッ素ホルモンをタグ付けする方法を成功裏に適用しました.
結論:
- 開発されたチオール-アルキニレーション手順は,迅速で,スケーラブルで,非常に汎用性があります.
- この方法は,アルキンの機能性を導入し,バイオコンジューゲーションの応用のための貴重なツールを提供します.
関連する概念動画
02:33Preparation and Reactions of Thiols
Thiols are prepared using the hydrosulfide anion as a nucleophile in a nucleophilic substitution reaction with alkyl halides. For instance, bromobutane reacts with sodium hydrosulfide to give butanethiol.
02:27Preparation of Alkynes: Alkylation Reaction
Introduction
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.
02:34Preparation of Alkynes: Dehydrohalogenation
Introduction
Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ammonia. The reaction proceeds with the loss of two equivalents of hydrogen halide (HX) via two successive E2 elimination reactions.
Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ammonia. The reaction proceeds with the loss of two equivalents of hydrogen halide (HX) via two successive E2 elimination reactions.
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.
02:26Preparation and Reactions of Sulfides
Sulfides are the sulfur analog of ethers, just as thiols are the sulfur analog of alcohol. Like ethers, sulfides also consist of two hydrocarbon groups bonded to the central sulfur atom. Depending upon the type of groups present, sulfides can be symmetrical or asymmetrical. Symmetrical sulfides can be prepared via an SN2 reaction between 2 equivalents of an alkyl halide and one equivalent of sodium sulfide.
01:38Preparation of Alcohols via Substitution Reactions
Overview
Alcohols can be synthesized from alkyl halides via nucleophilic substitution reactions. The highly polar carbon-halogen bond in the substrate makes halide a good leaving group. The hydroxide ion or water can act as a nucleophile to take the place of halide and form an alcohol. The substitution reactions occur via two different reaction pathways, SN1 or SN2, depending on the nature of carbon attached to the halide.
Primary alcohols are synthesized from primary alkyl halides, and the...
Alcohols can be synthesized from alkyl halides via nucleophilic substitution reactions. The highly polar carbon-halogen bond in the substrate makes halide a good leaving group. The hydroxide ion or water can act as a nucleophile to take the place of halide and form an alcohol. The substitution reactions occur via two different reaction pathways, SN1 or SN2, depending on the nature of carbon attached to the halide.
Primary alcohols are synthesized from primary alkyl halides, and the...