単純なMIDAボロナートから複合ボロン酸の多段階合成
Eric P Gillis1, Martin D Burke
1Roger Adams Laboratory, Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Journal of the American Chemical Society
|October 8, 2008
まとめ
空気に安定するMIDAボロナートは,合成化学の限界を克服しています. これらの安定化合物は,複雑なボロン酸の構成要素の複数段階の合成を可能にし,高度な有機合成を促進します.
科学分野:
- 有機化学 オーガニック・ケミストリー
- 合成化学 合成化学について
- 薬用化学 薬用化学について
背景:
- ボロン酸は有機合成において極めて重要であるが,多くの反応剤に対して敏感である.
- それらの不安定性は,合成戦略を制限する,後期的な導入を必要とします.
研究 の 目的:
- 複雑な分子合成のための安定したボロン酸の代用品を開発する.
- ボロン酸の構成要素を用いた多段階合成を可能にする.
主な方法:
- N-メチリミノアセチウム酸 (MIDA) ボロナートの合成と特徴付け.
- 一般的な合成反応剤との互換性に関する研究.
- X線結晶学および可変温度NMRスペクトロスコーピー.
- MIDAボロナートを使用した (+) -クロカシンCの総合合成.
主要な成果:
- MIDAボロナートは,空気や一般的な反応剤に対して,例外的な安定性を示しています.
- 安定性は,ボロンp軌道と窒素単一のペアの運動的アクセサビリティに起因する.
- イテラティブ・クロスカップリング反応における実証された有用性.
- (+) -クロカシンCのモジュール式全合成を達成した.
結論:
- MIDAボロナートは,ボロン酸の取り扱いと利用における重要な進歩を表しています.
- この方法論は,複雑なボロン酸誘導体の合成を簡素化します.
- 自然製品を含む複雑な分子構造の効率的な構築を可能にします.
関連する概念動画
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.
02:47Alkynes 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.
02:15Preparation 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...
03:08Rate-Determining Steps
Relating Reaction Mechanisms
In a multistep reaction mechanism, one of the elementary steps progresses significantly slower than the others. This slowest step is called the rate-limiting step (or rate-determining step). A reaction cannot proceed faster than its slowest step, and hence, the rate-determining step limits the overall reaction rate.
The concept of rate-determining step can be understood from the analogy of a 4-lane freeway with a short-stretch of traffic-bottleneck caused due to...
In a multistep reaction mechanism, one of the elementary steps progresses significantly slower than the others. This slowest step is called the rate-limiting step (or rate-determining step). A reaction cannot proceed faster than its slowest step, and hence, the rate-determining step limits the overall reaction rate.
The concept of rate-determining step can be understood from the analogy of a 4-lane freeway with a short-stretch of traffic-bottleneck caused due to...
02:23Alcohols from Carbonyl Compounds: Reduction
Reduction is a simple strategy to convert a carbonyl group to a hydroxyl group. The three major pathways to reduce carbonyls to alcohols are catalytic hydrogenation, hydride reduction, and borane reduction.
Catalytic hydrogenation is similar to the reduction of an alkene or alkyne by adding H2 across the pi bond in the presence of transition metal catalysts like Raney Ni, Pd–C, Pt, or Ru. Aldehydes and ketones can be reduced by this method, often under mild to moderate heat (25–100°C) and...
Catalytic hydrogenation is similar to the reduction of an alkene or alkyne by adding H2 across the pi bond in the presence of transition metal catalysts like Raney Ni, Pd–C, Pt, or Ru. Aldehydes and ketones can be reduced by this method, often under mild to moderate heat (25–100°C) and...