自由 (NH) ヘテロサイクルの酸化C-アリレーションは,直接 (sp3) C-H結合機能化によるものです
1Department of Chemistry, Columbia University, 3000 Broadway, New York, New York 10027, USA.
Journal of the American Chemical Society
|October 14, 2004
まとめ
新しい酸化C-アリレーション法により,飽和ヘテロサイクルのハロアレンと直接クロスカップリングが可能になる. この効率的な触媒プロセスは,単一のステップで価値あるヘテロサイクリック製品を生成します.
科学分野:
- 有機化学 オーガニック・ケミストリー
- カタリシス カタリシス カタリシス
- ヘテロサイクル化学 ヘテロサイクル化学
背景:
- 飽和したN-ヘテロサイクルは,医薬品や材料の重要な構成要素です.
- これらのヘテロサイクルの機能化のための効率的な方法,特にC-H活性化による方法は,非常に求められています.
- 既存の方法は,しばしば機能化前または厳しい条件を必要とします.
研究 の 目的:
- 飽和したN-ヘテロサイクルの直接的酸化C-アリレーションのための新しい触媒システムを開発する.
- 単一の合成操作でN-ヘテロサイクルとハロアレン間のクロスカップリングを達成するために.
- この新しい変革の範囲とメカニズムを探求する.
主な方法:
- ロジウム触媒反応システムの開発.
- 水素受容体としてテルトブチルエチレンを利用して,収穫量を向上させる.
- 温度,溶媒,触媒の負荷を含む反応条件の最適化.
- 運動イソトープ効果の研究を含むメカニズムに関する予備調査.
主要な成果:
- 様々な飽和したN-ヘテロサイクル (ピロリジン,ピペリジン,ピペラジン,モルフォリン) をハロ・ヘテロアレンで成功的に酸化C-アリレーションする.
- 価値あるヘテロサイクリック製品の高い収穫は,1つのステップで達成されます.
- ベータヒドリドの除去とカルボメタレーションを含む主要な触媒的ステップの特定.
- 運動同位体効果 (KIE = 4.3) は,β-ヒドリドの除去が速度を決定することを示唆しています.
結論:
- 飽和したN-ヘテロサイクルの酸化C-アリレーションのための新しい効率的な方法が確立されています.
- この反応は,複雑なヘテロサイクルの化合物への汎用的な経路を提供します.
- 機械学的洞察は,β-ヒドリドの除去の重要性と,選択性を制御するフォスフィンリガンドの役割を強調しています.
関連する概念動画
Oxidation of Alkenes: Syn Dihydroxylation with Osmium Tetraoxide
Alkenes are converted to 1,2-diols or glycols through a process called dihydroxylation. It involves the addition of two hydroxyl groups across the double bond with two different stereochemical approaches, namely anti and syn. Dihydroxylation using osmium tetroxide progresses with syn stereochemistry.
Oxidation of Alkenes: Anti Dihydroxylation with Peroxy Acids
Diols are compounds with two hydroxyl groups. In addition to syn dihydroxylation, diols can also be synthesized through the process of anti dihydroxylation. The process involves treating an alkene with a peroxycarboxylic acid to form an epoxide. Epoxides are highly strained three-membered rings with oxygen and two carbons occupying the corners of an equilateral triangle. This step is followed by ring-opening of the epoxide in the presence of an aqueous acid to give a trans diol.
Alkynes 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.
Alkynes to Carboxylic Acids: Oxidative Cleavage
Alkynes undergo oxidative cleavage in the presence of oxidizing reagents like potassium permanganate and ozone. The triple bond — one σ bond and two π bonds — is completely cleaved, and the alkyne is oxidized to carboxylic acids. When warm and basic aqueous potassium permanganate is used as an oxidizing agent, alkynes are first converted to carboxylate salts via an unstable α-diketone intermediate. Further, a mild acid treatment protonates the carboxylate anions generating free carboxylic acid...
ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3
All ortho–para directors, excluding halogens, are activating groups. These groups donate electrons to the ring, making the ring carbons electron-rich. Consequently, the reactivity of the aromatic ring towards electrophilic substitution increases. For instance, the nitration of anisole is about 10,000 times faster than the nitration of benzene. The electron-donating effect of the methoxy group in anisole activates the ortho and para positions on the ring and stabilizes the corresponding...
meta-Directing Deactivators: –NO2, –CN, –CHO, –⁠CO2R, –COR, –CO2H
All meta-directing substituents are deactivating groups. These substituents withdraw electrons from the aromatic ring, making the ring less reactive toward electrophilic substitution. For example, the nitration of nitrobenzene is 100,000 times slower than that of benzene because of the deactivating effect of the nitro group. The first step in an electrophilic aromatic substitution is the addition of an electrophile to form a resonance-stabilized carbocation. The energy diagrams for the...


