應用丙烯基醋酸酯合成四取代之呋喃與萘併呋喃

Abstract

合成多取代呋喃與呋喃衍生物為有機合成中具挑戰性及重要的一環，本文以丙烯基醋酸酯為前驅物，分別與容易取得的1,3-雙酮/α-拉電子取代基酮類起始物，經過一系列條件篩選及取代基探討，推測反應機構經由SN2’ 加成－脫去反應，進行Feist-Bénary type反應，合成高產率之四取代呋喃產物（up to 99%）。其中，以1,3-環戊酮為起始物，則得到吡喃為主產物。另一方面，若以萘醇為起始物，不需路易士酸催化，即進行Freidel-Crafts SN2'反應過程，接著，以oxa-Micheal 合環反應，有效合成萘併呋喃（up to 96%）。此方法能應用於丙烯基醋酸酯上，含有各種拉電子基、推電子基、雜環取代及烷基取代。然而，欲合成苯併吲哚並未得到預期結果，得到SN2反應而未環化的產物。Synthesis of polysubstituted furans and naphthofurans represent an important subclass in organic synthesis. Herein, we develop a new synthetic strategy for accessing tetrasubstituted furans by Feist-Bénary type reaction between allylic acetate precursor and 1,3-dicarbonyl/ α-withdrawing ketones. After studying a series of substrate scope under optimized conditions, we provided a reasonable mechanism. In this process, nucleophile attacks to Michael acceptor by SN2’ process, then undergo addition-elimination to give desired aromatic furan compounds（chemical yield up to 96% ）. The use of 1,3-cyclopentandione as starting material, pyran is obtained as major product. On the other hand, use of naphthol as starting material, reaction proceeded through Freidel-Crafts SN2' process followed by intramolecular oxa-Micheal cyclization and subsequently aromatization to give naphthofurans（chemical yield up to 96%）. This method can be applied to different functional groups on allylic acetates, such as electron-donating, electron-withdrawing, heteroaromatic and aliphatic groups. However, when 1-aminonaphthalene was used as the nucleophile, instead of the desired benzoindole, we got SN2 addition compound.