ベータ-ニトロアクリラートの有機触媒的非対称移転水素化:ベータ2-アミノ酸にアクセスする
Nolwenn J A Martin1, Xu Cheng, Benjamin List
1Max-Planck-Institut für Kohlenforschung, D-45470 Mülheim an der Ruhr, Germany.
Journal of the American Chemical Society
|September 26, 2008
まとめ
この研究は,β-ニトロアクリラートのJacobsenのチオウレア触媒還元を用いて,光学的に活性なβ2-アミノ酸を生成するための効率的な方法を示しています. この結合還元は,新しい合成経路における重要なステップである.
科学分野:
- 有機化学 オーガニック・ケミストリー
- アシンメトリック・シンセシス
背景:
- 光学的に活性なβ2-アミノ酸は,医薬品化学における貴重なキラル構成要素である.
- これらの化合物への効率的でエナチオセレクティブな合成経路の開発は,依然として大きな課題です.
研究 の 目的:
- 光学的に活性なβ2-アミノ酸のエナチオセレクティブ合成のための新しい高効率な方法を開発する.
- ハンツシュエステルの媒介によるベータ-ニトロアクリラートの結合還元を,ジェイコブセンチオウレア触媒によって触媒化するために利用します.
主な方法:
- ジャコブセンチオウレア触媒を用いて,非対称な触媒を用いる.
- 結合還元反応における還元剤としてハンツシュエステルを使用する.
- 合成の重要なステップとしてβ-ニトロアクリラートの減少に重点を置く.
主要な成果:
- ベータ-ニトロアクリラートの高効率でエナチオセレクティブの結合還元を達成しました.
- 光学的に活性なベータ2アミノ酸への新しい経路での方法の有用性を実証しました.
- ジャコブセンチオウレア触媒は,非対称な変換を媒介するのに有効であることが証明されました.
結論:
- 記述された方法は,光学的に活性なβ2-アミノ酸への新しい効果的な経路を提供します.
- エナチオセレクティブのハンツシュエステル媒介結合還元は,非対称合成のための強力なツールです.
- このアプローチは,キラル分子の合成におけるより広範な応用の可能性を提供します.
関連する概念動画
02:17Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
Catalytic hydrogenation of alkenes is a transition-metal catalyzed reduction of the double bond using molecular hydrogen to give alkanes. The mode of hydrogen addition follows syn stereochemistry.
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
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.
01:08Nitriles to Carboxylic Acids: Hydrolysis
Nitriles undergo acid-catalyzed hydrolysis or base-catalyzed hydrolysis to form a carboxylic acid. These reactions proceed via an amide intermediate.
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.
01:07Alkylation of β-Ketoester Enolates: Acetoacetic Ester Synthesis
Acetoacetic ester synthesis is a method to obtain ketones from alkyl halides and β-keto esters. The reaction occurs in the presence of an alkoxide base that abstracts the acidic proton of the β-keto esters. The step results in an enolate ion which is doubly stabilized. The enolate then reacts with an alkyl halide via the SN2 process to produce an alkylated ester intermediate with a new C–C bond. The hydrolysis of the intermediate, followed by acidification, results in an alkylated β-keto acid.