鈷催化共軛烯酮與炔類之不對稱還原偶合及[3+2]環化反應

Cobalt-Catalyzed Asymmetric Reductive Coupling and [3+2] Reductive Cycloaddition of Alkynes with Enones

韋竹鴻(Chu-Hung Wei)

指導教授 ： 鄭建鴻

國立清華大學/理學院/化學系/博士(2010年)

摘要

在本篇論文中，首先在CoI2/(R)-BINAP)/Zn/ZnI2催化系統下，以1,4-dioxane為溶劑、H2O為質子的來源，在室溫下反應24小時，將炔類(1a-1g)及環共軛烯酮(2a-2d)順利的進行分子間不對稱還原偶合反應，並且得到一系列具有高鏡像、立體、位向選擇率的多取代烯類衍生物。接著藉由產物2.3a、2.3f絕對結構的鑑定，更進一步的了解手性配位基在反應中間體中所造成的立體效應對於產物絕對結構的影響。
此外，分別在CoBr2/dppe/Mn/ZnCl2/CH3CN以及CoI2/BINAP/Zn/ZnI2/1,4-dioxane的催化系統下，不額外添加H2O為質子來源，在40oC下反應24小時，可將炔類(1a-1l)以及環共軛烯酮(2a-2e)順利的進行分子間[3+2]還原環化加成反應，並且得到一系列具有高立體選擇率之[2.2.1]及[3.2.1]雙碳環醇衍生物。此分子間[3+2]還原環化加成反應拓展炔類與共軛烯酮，在過渡金屬催化下新的反應類型。並且利用同位素實驗更進一步的了解反應機構。
最後我們延續上述分子間[3+2]還原環化加成反應，利用CoI2/(R,R′,S,S′)-Duanphos/Zn/ZnI2催化系統下，以1,4-dioxane為溶劑，在室溫下反應24小時，將炔類(1a-1i)以及環共軛烯酮(2a-2e)順利進行不對稱分子間[3+2]還原環化加成反應，並且得到一系列具有高鏡像及立體選擇率的[2.2.1]及[3.2.1]雙碳環醇衍生物。藉由產物3.3a絕對結構的鑑定，使得我們更進一步的了解手性配位基在反應機構中的影響。此外我們根據炔類與環共軛烯酮類化合物分別進行不對稱還原偶合反應以及不對稱[3+2]還原環化加成反應的結果，進一步探討此兩種反應的互相關係。

關鍵字

不對稱催化 ； 還原偶合反應 ； [3+2]還原環化加成反應

並列摘要

In the thesis, a CoI2/(R)-BINAP, Zn, ZnI2 and H2O system efficiently catalyzed the intermolecular asymmetric reductive coupling of alkynes (1a-1g) with cyclic enones (2a-2d) at room temperature for 24 hour to afford highly enantioselective β-substituted cyclic enones. The reaction proceeds with highly regio- and stereoselectivity. In addition, by identify the absolute configuration of products 2.3a and 2.3f, a possible mechanism that involves the formation of cobaltacyclopentene intermediate from alkyne and cyclic enone is proposed.
In addition, two different catalyzing system: CoBr2/dppe, Mn, ZnCl2, CH3CN and CoI2/BINAP, Zn, ZnI2, 1,4-dioxane, efficiently catalyzed the intermolecular reductive [3+2] cycloaddition of alkynes (1a-1l) with cyclic enones (2a-2e) at 40oC for 24 hour to afford highly stereoselective bicyclo[2.2.1]hept-2-en-1-ol and bicyclo[3.2.1]oct-6-en-1-ol derivatives respectively. This reaction also expanded a new reaction type of alkynes and enones in transition metal catalyzed reaction. We utilized the isotope experiment to further understand the mechanism.
. Finally, we developed a new system: CoI2/(R,R′,S,S′)-Duanphos, Zn, ZnI2, 1,4-dioxane, efficiently catalyzed the intermolecular asymmetric reductive [3+2] cycloaddition of alkynes (1a-1i) with cyclic enones (2a-2e) at room temperature for 24 hour to afford highly enantio- and stereoselective bicyclo[2.2.1]hept-2-en-1-ol and bicyclo[3.2.1]oct-6-
en-1-ol derivatives. In addition, by identify the absolute configuration of products 3.3a, a possible mechanism that involves the formation of cobaltacyclopentene intermediate from alkyne and cyclic enone is proposed. We discussed the result depend on alkyne and enones by asymmetric reductive coupling and asymmetric reductive [3+2] cycloaddition experiment, and further investigate the interdependent between these two reactions

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