導かれた金属 (オクソ) アリファティックC-H水酸化: 主要な基板バイアス
Marinus A Bigi1, Sean A Reed, M Christina White
1Department of Chemistry, Roger Adams Laboratory, University of Illinois, Urbana, Illinois 61801, USA.
Journal of the American Chemical Society
|May 22, 2012
まとめ
新しい誘導戦略は,金属触媒化C-H水酸化を誘導するためにカルボキシル酸基を用いる. このアプローチは固有のバイアスを克服し,パクリタキセルのような複雑な分子の正確な酸化を可能にします.
科学分野:
- 有機金属化学 有機金属化学
- オーガニック・シンセシス オーガニック・シンセシス
- カタリシス カタリシス カタリシス
背景:
- C-H水酸化は,有機合成における重要な変換である.
- 非ヘム鉄複合体は有望な触媒活性を提供するが,電子的およびステリック的要因による選択性の課題に直面している.
- サイト固有の機能化を実現するために,しばしばディレクター・グループが必要になります.
研究 の 目的:
- 金属 (オクソ) 誘導C−Hヒドロキシル化における誘導効果のための最初の一般的な戦略を記述する.
- カーボキシル酸分子が,鉄触媒C−H水酸化における不利なバイアスを克服する方法を実証する.
- 複雑な自然産物枠組におけるサイト固有の酸化を可能にするために.
主な方法:
- 非ヘム鉄複合体Fe (PDP) を触媒として使用した.
- カーボキシル酸の機能群を指向部分として含有する使用された基板.
- パクリタキセルフレームワークのC-H酸化を調査し,指向効果を証明しました.
主要な成果:
- カーボキシル酸グループは,電子的,ステリック的,ステレオ電子的バイアスを克服し,C-H水酸化を成功裏に導いた.
- 誘導効果は,パクリタセルの好ましいC-1経路から酸化を遠ざけた.
- パクリタキセルの自然酸化状態とステレオ構成でC-2酸化を確立しました.
結論:
- 炭酸酸を使用した金属 (オクソ) 促進C-H水酸化を誘導するための一般的な戦略が確立されています.
- この方法論は,挑戦的なC-H機能化反応におけるサイト選択性を制御するための強力なツールを提供します.
- このアプローチは,パクリタキセルの選択的酸化によって示される複雑な分子の合成を可能にします.
関連する概念動画
02:44Oxidation 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.
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.
02:36Regioselectivity 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.
01:25Radical 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.
02:04Oxidation 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.
03:08Hydroboration-Oxidation of Alkenes
In addition to the oxymercuration–demercuration method, which converts the alkenes to alcohols with Markovnikov orientation, a complementary hydroboration-oxidation method yields the anti-Markovnikov product. The hydroboration reaction, discovered in 1959 by H.C. Brown, involves the addition of a B–H bond of borane to an alkene giving an organoborane intermediate. The oxidation of this intermediate with basic hydrogen peroxide forms an alcohol.