I. 分子內Wittig反應得到雜環化合物：簡易合成異噁唑及4H-苯並吡喃衍生物 II. 經有機鹼催化進行區域選擇性Aza-1,4-加成或Aza-1,6-加成之連續反應合成(螺環)四氫喹啉衍生物

Abstract

I. 分子內Wittig反應得到雜環化合物：簡易合成異噁唑及4H-苯並吡喃衍生物

第一章：透過有機鏻鹽經由分子內 Wittig 反應合成雙取代異噁唑 經由一連串反應條件優化，成功地透過本實驗室先前開發之製備呋喃、噁唑化合物合成策略應用於合成具有生物活性之異噁唑衍生物。我們利用穩定、製備方法簡單的有機鏻鹽作為起始物，在溫和的反應條件下建立出一個高效率的氧醯化反應、分子內Wittig反應合成雙取代異噁唑，透過一鍋化反應亦表現良好。

第二章：通過分子內Wittig反應化學選擇性合成異噁唑和4H-苯並吡喃衍生物 延續第一章的概念進而發展起始物衍生化，調控其化學選擇性合成出異噁唑及苯並吡喃衍生物。實驗過程中我們找到在不同的溶劑中反應會得到兩者不同雜環結構之產物，使用四氫呋喃 (THF) 作為溶劑時，會進行醯基轉移/分子內Wittig反應，得到異噁唑衍生物；而在二氯甲烷 (CH2Cl2) 作為溶劑的條件下，則會進行化學選擇性Wittig反應，產物傾向得到4H-苯並吡喃衍生物。

II. 經有機鹼催化進行區域選擇性Aza-1,4-加成或Aza-1,6-加成之連續反應合成(螺環)四氫喹啉衍生物

本研究開發出一種利用對亞基苯醌衍生物與1,3-茚二酮衍生物合成出具有兩種不同骨架的四氫喹啉化合物之策略。透過4-二甲氨基吡啶(DMAP)則是進行aza-Michael addition/1,6-addition得到具有兼具螺環結構的四氫喹啉產物；若是透過四甲基胍(TMG)即進行aza-1,6-addition/vinylogous 1,6-additon得到[4+2]環加成產物；經由此催化系統控制展現出卓越的區域選擇性反應結果。

I. An Intramolecular Wittig Approach toward Heteroarenes: Synthesis of Isoxazoles and Chromenone-oximes: (i) Phosphine-Mediated Synthesis of Di-substituted Isoxazoles via Intramolecular Wittig Reaction: Motivated by our previously successful reports on the furans and oxazoles synthesis, here we extended our intramolecular Wittig reaction strategy to construct potentially bio-active isoxazoles. To begin with, a series of stable isolable phosphonium salts were generated from α-halo ketoximes and further subjected to a tandem O-acylation/intramolecular Wittig reaction affording isoxazoles under mild conditions. Moreover, a one-pot protocol was also realized from a direct transformation of α-halo ketoximes in moderate to good yields.

(ii) Chemoselective Synthesis of Substituted 4H-Chromene and Isoxazole Derivatives via Intramolecular Wittig reaction: In continuation of our concept, o-hydroxyl α-halo ketoximes were used for developing the chemoselective synthesis of isoxazoles and 4H-chromenes derivatives. During the study, we found that the reaction in different solvents will result in two different heterocycles. When tetrahydrofuran (THF) was used as the solvent, it underwent O-acylation / intramolecular Wittig reaction to obtain isoxazole derivatives. On the other hand, a chemoselective Wittig reaction was found to result in 4H-chromene derivatives with the usage of dichloromethane (CH2Cl2) as the solvent.

II. Base-controlled Regioselective Aza-1,4 / Aza-1,6-addition Cascade Reaction for Synthesis of Tetrahydroquinoline Derivatives: A strategy was developed for synthesizing two tetrahydroquinoline derivatives with different skeletons by using para-quinone methide and 1,3-indandione derivatives. In the reaction condition using dimethylaminopyridine (DMAP) as the catalyst, the reaction underwent smoothly via aza-Michael addition/1,6-addition to obtain spirotetrahydroquinoline products. While 1,1,3,3-Tetramethylguanidine (TMG) was employed as the catalyst, [4+2] cycloadducts were furnished via aza-1,6-addition/vinylogous 1,6-addition. Excellent regioselectivities were observed in both of these catalytic systems.