α-亞甲基-β−胺基酯進行高立體位向選擇性麥可加成反應

A Highly Diastereoselective Michael Addtion Reaction on α-Methylene-β-amino ester

李格睿(Ge-Ray Lee)

指導教授 ： 李世元

淡江大學/理學院/化學學系碩士班/碩士(2006年)

https://doi.org/10.6846/TKU.2006.00934

摘要

β-環內醯胺(β-Lactam)為許多天然物以及藥物的基本架構，而其環上取代基的立體位置更是影響其生物活性功能的重要因素，α-甲基胺-β-胺基酯(α-Aminomethyl-β-amimoester)為β-環內醯胺之前驅物，因此研發其立體選擇性的不對稱合成(Asymmetric synthesis)方法為我們研究的目標之ㄧ；一般是利用反應物本身的立體輔助官能基或添加具有對掌性的(Chiral)催化劑來提升反應的立體選擇性，而我們研究發展在無任何光學活性輔助的環境下(Achiral)，利用麥可加成(Michael Addition)反應得到高產率及高立體選擇性的成果。
我們將一系列外消旋(Racemic)的α-亞甲基-β-胺基酯(α-Methylene-β-amimoester)與胺類化合物(Amine)進行麥可加成反應，在無溶劑(Neat)的狀態下與胺類化合物(5 mL/1 mmol)反應，得到以syn 為主的α-甲基胺-β-胺基酯，另一加入三氟化硼(BF3．OEt2, 1.5 eq.)與胺類化合物(5.0 eq.)反應可得到以anti 為主的α-甲基胺-β-胺基酯；我們將α-甲基胺-β-胺基酯進行環化反應可合成β-環內醯胺，進
而証明α-甲基胺-β-胺基酯的立體化學結構。

關鍵字

高立體位向性

並列摘要

β-Lactams are the main structural moiety of numerous biological active molecules, and its stereochemistry is one of the key factor that influences the effectiveness. α-Aminomethyl-β-amimoesters are important synthetic precursors for β-lactams, therefore developing its stereoselective reaction is useful in organic synthesis. The asymmetric synthesis is generally achieved by using chiral catalyst or chiral auxiliary to afford the requirement. We develop a new and mild synthetic method which successfully control diastereoselectivity via Michael addition reaction under a achiral reaction condition.
A series of racemic α-methylene-β-amimoesters was reacted with amines under the reaction conditions. The diastereoselcetivity can be manipulated by treatment of
the amount of amine and trifloroboran. The α-aminomethyl-β-amimoester was converted to the corresponding β-lactam by treatment of LHMDS. The cyclization not only proves stereochemistry of α-aminomethyl-β-amimoesters, but also improves this diastereoselective reaction much more useful in organic synthesis.

並列關鍵字

Diastereoselectivity ； Achiral reaction ； Michael addition

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