鎳與鈷金屬錯合物催化偶合及環化反應之研究

Nickel and Cobalt-Catalyzed Coupling and Cyclization Reactions

張宏泰(Hong-Tai Chang)

指導教授 ： 鄭建鴻

國立清華大學/理學院/化學系/博士(2007年)

https://doi.org/10.6843/NTHU.2007.00182

摘要

中文摘要
本文主要探討鎳及鈷金屬錯合物的催化反應。在第一部份中，我們將主要探討phthalides的合成。Phthalide是一芳香環並帶有五環環酯化合物；而phthalide的類衍生物廣泛的存在於許多高等植物當中，其具有許多生理活性物質，特別的是具有殺菌、除草、止痛、利尿和抗高血壓..等活性。在第二章中，我們將分別介紹利用鎳及鈷金屬錯合物催化鄰-鹵苯甲酸甲酯化合物與醛類進行偶合環化反應，得到許多phthalide類衍生物，而不需要用到具有毒性的一氧化碳氣體。而在鈷金屬催化反應中，若使用具有光學活性配位基的鈷錯化合物作為催化劑，則可以得到具光學活性的phthalides產物，可以更廣泛的被應用。
在第二部份中，我們將探討[2+2+2]環化加成反應。在第三章中，我們藉由鈷金屬錯合物催化propiolates與alkynyl alcohols進行分子間及分子內的[2+2+2]環化加成反應，進而進行環酯化反應得到環酯化合物，可利用於合成五環的phthalides類衍生物及六環、七環環酯化合物、環醯化合物..等具有許多廣泛生物活性的分子結構。在第四章中，我們針對鈷金屬催化劑進行[2+2+2]環化加成反應，催化末端有較大立體障礙之芳香環取代基的雙炔類與有機烷氰化物，進行反應得到具有多芳香環取代的pyridine環產物。同時利用其催化特性，我們設計了單一分子具有雙炔與有機烷氰化合物的分子結構 (nitrilediynes)，同樣在鈷金屬錯合物的系統催化下，成功地進行[2+2+2]環化加成反應，得到polycyclopyridine化合物。
在第三部份中，主要探討還原偶合反應。在第五章中，我們嘗試以鈷金屬錯合物CoI2(dppe)/Zn/ZnI2催化系統下，催化炔類與有機烯酮類或有機烯醛類進行還原偶合反應，得到了不錯的結果，分別具有很好的位向及立體選擇性。此合成法延續之前的先前本實驗室無法進行的還原偶合反應，將有助於這類衍生物的合成；同時我們以此為反應基本條件，加以設計出一enyne分子結構，其同時包含炔類與共軛烯類的化合物，進行分子內還原偶合反應，得到一系列具有環外雙鍵的還原偶合環化之五環產物。
反應若改以催化1,2-雙烯類與有機烯酮類進行還原偶合反應，發現會進一步再進行環化反應，得到簡單且直接的[3+2]還原偶合產物，具有不錯立體及位向選擇性結果，希望可以藉由此反應合成出更多有經濟價值的化合物。

關鍵字

偶合環化反應 ； 光學活性配位基 ； [2+2+2]環化加成反應 ； 環酯化反應 ； 還原偶合反應 ； [3+2]還原偶合反應

並列摘要

Abstract
Phthalides (isobenzofuranones) are five-membered lactones found in plants. These species possess several important properties such as fungicidal, bacteriocidal, herbicidal and analgesic activities. In chapter 2, we report a novel efficient method for the synthesis of phthalides via a nickel-catalyzed cyclization of o-halobenzoates with aldehydes is described. The reaction of o-bromobenzoate with benzaldehyde in the presence of Ni(dppe)Br2 and zinc metal powder in THF for 24 h at reflux temperature afforded the corresponding phthalide derivatives in good to excellent yields and in high chemoselectivity. On the other hand, treatment of 2-iodobenzoate with benzaldehyde in the presence of a mixture of CoI2(dppe) and zinc metal powder in THF at reflux temperature also led to the cocyclization of phthalide derivative in good yields. This new cyclization reaction provide convenient method for the synthesis of various substituted phthalides in good to excellent yields from easily available starting materials.
The transition metal catalyzed [2+2+2] cycloaddition reaction of unsaturated molecules is an efficient method to construct six-membered cyclic compounds with the formation of three new carbon-carbon bonds. However, versions of [2+2+2] cycloaddition generally have encountered difficulties in the control of chemo- and regioselectivity. In chapter 3, we report a cobalt catalyzed [2+2+2] cycloaddition reaction of alkynyl alcohols and amines with propiolates and diynes to give various substituted benzolactones and lactams with high chemo- and regioselectivity in good to excellent yields.
The preparation of complex polycyclic pyridine derivatives is an important synthetic goal, because of the utility of these molecules as potential pharmaceuticals. Transition metal-catalyzed [2+2+2] cocyclotrimerization of two alkynes with a nitrile is one of the attractive methods to construct polycyclic pyridine derivatives in highly atom-economical manner. In chapter 4, we report a cobalt catalyzed partially intermolecular cocyclotrimerization of diynes with alkylnitrile to form pyridine derivatives in modest to high yield. We also reported an intramolecular cocyclotrimerization of nitrilediynes to afford polycyclic pyridine derivatives in good to excellent yields.
In chapter 5, a cobalt complex/Zn system effectively catalyzes the reductive coupling of alkenes and alkynes in the presence of water to give highly substituted alkenes in very high yields. The reaction of enones and enals requires the use of CoI2(dppe)/Zn/ZnI2 system. The reductive coupling of enones and alkynes also work efficiently in intramolecular way.
During the course of our investigation in related reductive coupling reactions we noticed that allenes and enones effectively cyclized to form cyclopentanols with very high diastereoselectivity. Thus, treatment of phenyl allene with methyl vinyl ketone in the presence of CoI2(dppe), Zn, ZnI2 and water in CH3CN gave 3-methylenecyclopentanol derivative in very good yield. The reaction also exhibited excellent chemo- and regioselectivity.

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