苯雜環衍生物的新法合成: (一) 雙氫黃酮素、(二) 2- 取代-3-苯甲基苯駢呋喃和 (三) 3,4-二氫異喹啉-1(2H)-酮

New syntheses of benzoheterocyclic derivatives: (i) flavanones; (ii) 2-substituted 3-benzylbenzofurans and (iii) 3,4-dihydroisoquinolin-1(2H)-ones

陳伯淵(Po-Yuan Chen)

指導教授 ： 王英基

高雄醫學大學/生命科學院/醫藥暨應用化學研究所/博士(2012年)

摘要

第ㄧ章
此研究在溫和而且環保的反應條件下新路徑合成雙氫黃酮類化合物，由o-hydroxyacetophenones (I-1) 和 benzaldehydes (I-2) 在水中反應生成中間體3-hydroxy-1-(2-hydroxylphenyl)-3-arylpropan-1-ones (I-3a-i)，再經由分子內Mitsunobu’s反應進行環化脫水或者在一鍋反應中以o-hydroxyacetophenones 和 benzaldehydes進行反應，生成高產率的雙氫黃酮類化合物 (I-4a-i)。

第二章
此研究利用tert-BuOK存在下進行碳陰離子-炔分子內環化反應合成2-取代-3-苯甲基苯駢呋喃化合物的方法，此為一個溫和有效率且具有位向選擇性，先以市售o-鄰碘苯酚(II-1)經由O-烷基化和Sonogashira反應可生成2-(2-phenylethynylphenoxy)-1-arylalkanones (II-5)，再以化合物II-5和tert-BuOK進行分子內碳陰離子-炔 5-exo-dig 環化反應，即可得到高產率的2-取代-3-苯甲基苯駢呋喃化合物。

第三章
本研究建立新穎且具化學選擇性的二氫異喹啉-1(2H)-酮化合物合成法，利用異香草素為起始物經五個步驟所合成的中間體o-oxiranylmethylbenzonitrile和氰化鈉/溴化四正丁基銨在一鍋中進行反應後，就能得到多取代二氫異喹啉-1(2H)-酮的目標產物。

關鍵字

雙氫黃酮素 ； 2- 取代-3-苯甲基苯駢呋喃 ； 3,4-二氫異喹啉-1(2H)-酮

並列摘要

Chapter I
Mild and environmentally benign methods for the syntheses of flavanones are described. The reaction of o-hydroxyacetophenones (I-1) and benzaldehydes (I-2) in water in the presence of DABCO at room temperature gave 3-hydroxy-1-(2-hydroxylphenyl)-3-arylpropan-1-ones (I-3a-i) as intermediates. Followed by an intramolecular dehydration of the 3a-i with the modified Mitsunobu’s reaction, the target flavanones (I-4a-i) were obtained. Moreover, the reaction of I-1 and I-2 at the same conditions but at reflux gave flavanones in one pot with good yields.

Chapter II
A mild, efficient, and regioselective carbanion-yne intramolecular cyclization which was mediated by tert-BuOK for the synthesis of 2-substituted 3-benzylbenzofurans, are developed. It was started from o-iodophenol (II-1), based on O-alkylation, and the Sonogashira reaction in sequence to produce 2-(2-phenylethynylphenoxy)-1-arylalkanones (II-5). An intramolecular carbanion-yne 5-exo-dig cyclization reaction of II-5 which was mediated by tert-BuOK yielded title benzofurans in good yields.

Chapter III
A novel synthesis of substituted 3,4-dihydroisoquinolin-1(2H)-ones is described. o-Oxiranylmethylbenzonitriles, prepared from isovanillin via five synthetic steps, were treated with NaCN/ tetra-n-butylammonium bromide (TBAB) to yield 3,4-dihydroisoquinolin-1(2H)-ones in good yields. This one pot reaction demonstrates the novel and chemoselective nature of ring-opening of epoxide by cyanide to generate an iminoisochroman ring via cyclization, again ring-opening by cyanide to generate a Michael acceptor and a donor, and ring re-cyclization through an intramolecular conjugate addition. The detailed mechanism is also rationally proposed.

並列關鍵字

flavanones ； 2-substituted 3-benzylbenzofurans ； 3,4-dihydroisoquinolin-1(2H)-ones

參考文獻

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