二氧化的固态异性SN2@P反应:实验和理论研究
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
概括
与基试剂一起开启oxazaphospholidines的固态分离环开放,为奇拉化合物提供了一条新的途径. 这种方法允许从单个辅助中合成关键的P-类固醇中间体的两个反体.
科学领域:
- 有机化学 有机化学
- 有机化学化学 有机化学
- 立体化学是一种立体化学.
背景情况:
- 氧扎聚胺是有机化学中的多功能中间体.
- 控制中心的立体化学对于合成性分子至关重要.
- 之前的研究表明,在oxazaphospholidine环开放反应中,立体化学结果各不相同.
研究的目的:
- 使用基试剂,研究2 - 氧化聚胺的立体分离环开放.
- 阐明控制中心立体化学结果 (反转与保留) 的机制.
- 为了证明从单个氨基醇辅助物中合成P-类固醇中间体的两个反体.
主要方法:
- 立体选择性环开反应的N-H和N-Me氧化与基试剂.
- 使用奇拉性氨基醇辅助剂 ((+) -cis-1-amino-2-indanol和 (-) - norephedrine) 合成oxazaphospholidines.
- 密度函数理论 (DFT) 的计算模型反应机制和过渡状态.
主要成果:
- N-H oxazaphospholidines经历了高度刻板选择的环开放,在中扭转了配置.
- N-Me氧化聚胺产生环开产物,在中保持配置.
- DFT研究显示,N-H基质的单阶段S(N) 2@P后侧攻击和N-Me基质的双阶段前侧攻击.
- BH3组充当指导组,与试剂进行协调.
结论:
- 建立了P-类固醇中间体的立体分离合成策略.
- 选择N替代剂 (H与Me) 决定了立体化学结果 (反转与保留).
- DFT计算为观察到的立体选择性提供了机制性的洞察力,突出了指导BH3组的作用.
相关概念视频
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...
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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.
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02:15Preparation of Alcohols via Addition Reactions
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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...