(一.)經化學選擇性分子內Wittig反應合成異噁唑、4H-苯並吡喃衍生物 (二.)經磷-1,6-加成/氧-醯化/δ-碳-醯化/分子內Wittig反應之多樣性導向合成螺環吡唑啉酮、1H-㗁呯[2,3-c]吡唑衍生物

Abstract

第一部分： 第一部分為延續先前本實驗室利用α-鹵代酮肟 (α-haloketoxime) 作為起始物建構雙取代異噁唑衍生物的合成方法，並在起始物骨架的設計上新增額外的一個鄰位酯基，進而優化反應條件、調控其化學選擇性、進行一鍋化反應可以建構兩種不同骨架的產物，實驗過程中我們找到在不同的溶劑中反應會傾向得到不同的產物，使用四氫呋喃作為溶劑時，會進行醯基轉移/分子內Wittig反應，進而得到異噁唑衍生物；而在二氯甲烷作為溶劑的條件下，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，兩者皆可以在溫和的條件下以良好的化學選擇性建構而成。

第二部份： 第二部分為利用α,β,γ,δ-不飽和吡唑啉酮 (α,β,γ,δ-Unsaturated Pyrazolones) 作為起始物進行多樣性導向合成，主要藉由取代基的立體效應、反應溶劑以及條件的優化可以控制化學選擇性，進而調控多樣性導向合成之反應走向。在此合成方法中，反應經由有機膦試劑進行1,6加成/氧-醯化反應可以形成七員環betaine中間體，在較大立體障礙的官能基條件下可以直接進行分子內Wittig反應得到七員環–1H-㗁呯[2,3-c]吡唑衍生物；而在沒有明顯立體障礙時則會進行非預期的δ-碳-醯化/環化/分子內Wittig反應得到螺環吡唑啉酮衍生物，兩個骨架的產物皆可以在溫合的條件下以良好的化學選擇性控制建構而成。Part 1: To continue our interests in constructing isoxazoles using intramolecular Wittig strategy, we had designed a new series of o-esteryl α-haloketoximes as a chemoselective reaction research target. With the optimized condition in hand, the desired disubstituted isoxazoles and 4H-chromenone-oximes were constructed chemoselectively in a diversity-oriented manner. Moreover, the selection of solvent was found to be crucial for the selectivity. While THF as the solvent, the reaction underwent an acyl transformation/intramolecular Wittig reaction sequence resulted in rearranged isoxazole derivatives. Whereas running the reaction in dichloromethane, 4H-chromenone-oximes were obtained through a direct chemoselective Wittig reaction without acyl group migration. Both products were obtained in excellent chemoselectivities and good to excellent yields under mild reaction conditions.

Part 2: We have developed an efficient method for the diversity-oriented synthesis of spiropentadiene pyrazolones and 1H-oxepino[2,3-c]pyrazoles in good to excellent yields under mild reaction conditions. The two products were formed via a tandem phospha-1,6-addition of PBu3 to α,β,γ,δ-unsaturated pyrazolones, followed by an O-acylation, chemoselective betaine formation, and finally a δ-C-acylation/Wittig reaction or direct Wittig reaction, respectively. A plausible model and mechanism were proposed to explain that the chemoselectivity was mainly controlled by the steric and solvent effects along with some minor factors from other conditions.