ボランオキサザフォスホリジンのステレオ変異性SN2@P反応:実験的および理論的研究
Hester Zijlstra1, Thierry León, Abel de Cózar
1Department of Theoretical Chemistry, Amsterdam Center for Multiscale Modeling, VU University Amsterdam, De Boelelaan 1083, NL-1081 HV Amsterdam, The Netherlands.
Journal of the American Chemical Society
|February 27, 2013
まとめ
アルキルリチウム反応剤によるオクサザフォスフォリジンのステレオダイバーゲント環開きは,キラルリン酸化物化合物への新しい経路を提供します. この方法により,主要なP-ステロゲン中間物質の両方のエナチオメールを1つの補助物質から合成することができます.
科学分野:
- 有機化学 オーガニック・ケミストリー
- オーガノフォスファルス 化学 化学
- ステレオ化学 ステレオ化学
背景:
- オクサザフォスフォリジンは,有機リン化学における多用途の中間物質である.
- リンセンターでのステレオ化学の制御は,キラル分子の合成に不可欠です.
- 以前の研究では,オクサザフォスフォリジンのリング開き反応において,異なるステレオ化学的結果が示されました.
研究 の 目的:
- アルキルリチウム反応剤を用いて,2-フェニルオクサザフォスホリジンのステレオダイバージェントリング開封を調査する.
- リンセンターにおけるステレオ化学的結果 (逆転対保持) を制御するメカニズムを解明する.
- 単一のアミノアルコールの補助体からP-ステロゲン介質の両方のエナンチオメアの合成を実証する.
主な方法:
- N-HおよびN-Meオキサザフォスホリジンのステレオ選択環開き反応は,アルキルリチウム反応剤によるものです.
- キラルアミノアルコールの補助物質 ((+) -シス-1-アミノ-2-インダノールと (-) -ノレフェドリン) を用いてオキサザフォスフォリジンの合成.
- 反応機構と移行状態をモデル化するために,密度関数理論 (DFT) の計算を行う.
主要な成果:
- N-Hオキサザフォスホリジンは,高度にステレオセレクティブのリング開きを経験し,リンで構成の逆転をします.
- N-Meオキサザフォスホリジンは,リンスで構成を保持したリング開き製品を生成します.
- DFTの研究では,N-H基板に対する単段階のS(N) 2@Pバックサイド攻撃と,N-Me基板に対する2段階のフロントサイド攻撃が明らかにされています.
- BH3グループは,リチウム反応剤と連携し,指向グループとして機能します.
結論:
- P-ステロゲン中間物質のためのステレオダイバーゲント合成戦略が確立されています.
- N置換物 (H対Me) の選択は,ステレオ化学的結果 (逆転対保持) を決定する.
- DFT計算は,観察されたステレオ選択性に関するメカニズム的な洞察を提供し,指導するBH3グループの役割を強調します.
関連する概念動画
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.
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.
02:23SN2 Reaction: Stereochemistry
In an SN2 reaction, the nucleophilic attack on the substrate and departure of the leaving group occurs simultaneously through a transition state. As the nucleophile approaches the substrate from the back-side, the configuration of the substrate carbon changes from tetrahedral to trigonal bipyramidal and then back to tetrahedral, leading to an inversion in the configuration of the product.
If the substrate is an achiral molecule at the α-carbon, the inversion of configuration is not observed.
If the substrate is an achiral molecule at the α-carbon, the inversion of configuration is not observed.
03:24Hybridization of Atomic Orbitals I
The mathematical expression known as the wave function, ψ, contains information about each orbital and the wavelike properties of electrons in an isolated atom. When atoms are bound together in a molecule, the wave functions combine to produce new mathematical descriptions that have different shapes. This process of combining the wave functions for atomic orbitals is called hybridization and is mathematically accomplished by the linear combination of atomic orbitals. The new orbitals that...
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...