アリル塩化物からパラジウム触媒による直接ボロン酸合成:様々なボロナートエステル誘導体への簡素化された経路
Gary A Molander1, Sarah L J Trice, Spencer D Dreher
1Roy and Diana Vagelos Laboratories and Penn/Merck Laboratory for High Throughput Experimentation, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323, United States. gmolandr@sas.upenn.edu
Journal of the American Chemical Society
|November 26, 2010
まとめ
パラジウムで触媒化された新しい方法は,アリル塩化物から直接アリルボロン酸を合成します. この効率的なプロセスは,それらを安定したトリフルオロボラート誘導体に変換し,スズキ-ミヤウラ結合のようなさらなる反応を可能にします.
科学分野:
- 有機化学 オーガニック・ケミストリー
- カタリシス カタリシス カタリシス
- 合成方法論 合成方法論
背景:
- ボロン酸およびその誘導体の基本的調製に関する限られた研究.
- ボロン酸合成の現在の方法は間接的,厳しい,または高価です.
研究 の 目的:
- アリルボロン酸の直接的かつ効率的な合成を開発する.
- ボロン酸を安定した誘導体に変換するための堅牢な方法を確立する.
- 合成されたボロン化合物を用いて効率的なクロスカップリング反応を可能にします.
主な方法:
- アリル塩化物からアリルボロン酸のパラジウム触媒による直接合成.
- 活用されたテトラヒドロキシジボロン (B2(OH) 4) は,不足した使用反応剤として.
- ボロン酸をトリフローロボラート誘導体に in-situ 変換する.
主要な成果:
- アリルボロン酸の効率的な合成を達成した.
- トリフローロボラート誘導体の加工なしでの良好から優れた収量が得られる.
- 様々な有用なボロナートへの容易な変換が実証されています.
- アリル塩化物のスズキ・ミヤウラ結合のための2段階1鍋の方法を開発した.
結論:
- 報告された方法は,アリルボロン酸およびその誘導体へのシンプルで効率的な経路を提供します.
- トリフロンボラートへの in-situ 変換は,安定性と有用性を高めます.
- ワンポット・カップリング・メソッドは,複雑な分子の合成を効率化します.
関連する概念動画
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.
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.
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.
02:15Preparation of Alcohols via Addition Reactions
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...
01:15α-Bromination of Carboxylic Acids: Hell–Volhard–Zelinski Reaction
The method to achieve α-brominated carboxylic acids using a mixture of phosphorus tribromide and bromine is known as the Hell–Volhard–Zelinski reaction. The reaction is catalyzed by phosphorus tribromide, which can be used directly or produced in situ from red phosphorus and bromine. The mechanism comprises PBr3 catalyzed conversion of acid to acid bromide and hydrogen bromide. The acid bromide enolizes to its enol form in the presence of HBr. The nucleophilic enol attacks the bromine molecule...
01:14Alkylation of β-Diester Enolates: Malonic Ester Synthesis
Malonic ester synthesis is a method to obtain α substituted carboxylic acids from ꞵ-diesters such as diethyl malonate and alkyl halides.