林文偉Lin, Wen-Wei侯柏志Hou, Bo-Jhih2022-06-082026-06-292022-06-082021https://etds.lib.ntnu.edu.tw/thesis/detail/48820cd26cbfde52731a013990cc7cd5/http://rportal.lib.ntnu.edu.tw/handle/20.500.12235/117211第一部分 論文第一部分研究是藉由Morita-Baylis–Hillman reaction (MBH型) /醯基轉移/ Wittig反應策略建構出2,3-雙取代呋喃[3,2-c]香豆素。反應是藉由有機磷試劑對末端炔酸酯進行MBH型反應生成鏻兩性離子，再與醯氯進行氧醯化反應，經醯基轉移/分子內Wittig反應建構出官能化呋喃[3,2-c]香豆素。而此方法也可適用於內部炔酸酯作為起始物，進行另一種MBH型/分子內Wittig反應生成雙取代呋喃[3,2-c]香豆素。在兩個策略皆能得到良好的產率，特別是在第二個策略亦可藉由置換起始物為內部炔醯胺進而生成呋喃[3,2-c]喹啉酮的產物。 本研究也透過數個控制實驗，驗證了反應機制的走向，並經由X-ray單晶繞射鑑定出關鍵的鏻兩性離子中間體，除此之外本策略亦適用於克級反應，對於之後的量化具有很大的潛力。 第二部分 延續第一部分研究在MBH型反應上的成功，因此論文的第二部分我們嘗試使用類似於MBH型反應的Rauhut–Currier reaction（RC型反應）來進行探討。因此我們延伸第一部分起始物的骨架設計出含羥吲哚的末端炔酸酯，藉由磷試劑對羥吲哚末端炔酸酯進行RC型反應生成鏻兩性離子，接著再與醯氯進行氧酰化反應，經酰基轉移/分子內Wittig反應，建構出羥吲哚螺環戊[c]色烯。在起始物的部分除了原先使用的羥吲哚骨架外，亦可藉由引入不同雜環化合物來得到不同種類的螺環戊[c]色烯。最後我們也經由數個控制實驗及使用非環類雙酮骨架的炔酸酯作為起始物，驗證了本策略的反應機制。Part I We have developed an highly efficient method for the construction of functionalized furo[3,2-c]coumarins from the terminal alkynoate and acyl chloride via MBH-type/acyl transfer/Wittig reaction sequence. The O-acylation of zwitterion which is generated by the MBH-type reaction of PPh3 to the alkynoate, can further provide the betaine intermediate in the presence of DIPEA. The betaine intermediate proceeded an unprecedented O- to C-acyl transfer, resulting in the functionalized furo[3,2-c]coumarins. This protocol could also be applicable to internal alkynoates for the synthesis of another type of 2,3-disubstituted furo[3,2-c]coumarins via MBH-type/intramolecular Wittig reactions as key steps.To investigate the mechanism, we have performed several control experiments and we prove that acyl transfer between O-to C-acylation by using acyl chloride addition sequence and was confirmed by X-ray analysis. Also this methodology could also be practically demonstrated on a gram scale synthesis.Part II An unprecedented phosphine-mediated reaction for the construction of spirocyclopenta[c]chromene-indolinones is reported via a Rauhut-Currier (RC)-type/acyl transfer/Wittig sequence. This methodology attributes the chemoselective phosphine addition to the alkynoate which generates the phosphorus zwitterion via RC-type reaction, and that further undergoes O-acylation to form the seven-membered betaine intermediate with acyl chloride in the presence of base. Extensive investigations revealthat the exceptional δ-acylation occurs through the C-O bond cleavage upon the seven-membered betaine, and the subsequent Wittig reaction would preferentially result in the aforementioned spiro compounds. Furthermore, our protocol could also be applicable to different alkynoates to provide a series of valuable spirocyclopenta[c]chromenones bearing privileged skeletons.MBH 型反應RC 型反應分子內Wittig 反應醯基轉移呋喃[32-c]香豆素呋喃[32-c]喹啉酮吲哚螺環戊[c]色烯MBH reactionRC reactionWittig strategyAcyl transferFuro[32-c]coumarinFuro[32-c]quinolinoneSpirocyclopenta[c]chromene-indolinones學術論文