吲哚酚的鈀金屬催化α-芳基化反應

本研究主要講述吲哚酚化合物進行鈀金屬催化α-芳基化反應的優化過程及結果。以市售的吲哚-3-醛 (Indole-3-carboxaldehyde)為起始物，製備出吲哚酚 (indoxyl)，再利用吲哚酚為前驅物，進行以鹼為媒介的烷基化反應，即可成功合成出一系列不同烷基取代的吲哚酚化合物。在α-烷基吲哚酚的鈀金屬催化α-芳基化反應中，我們經過與多種鹼、配位基、鈀金屬來源及溶劑的測試以後，找出了以碳酸銫 (Cs2CO3)為鹼、雙(二亞苄基丙酮)鈀 (Pd(dba)2) (6 mol %)與金剛烷基膦 (P(Ad)3) (8 mol %)為催化劑，以四氫呋喃 (THF)及1,4-二噁烷 (Dioxane)為共溶劑的最佳條件。我們用多種不同的溴化芳基，如含有推電子基、拉電子基、雜環類等，在吲哚酚的α位進行芳基化，建立一個含有芳烴官能基的四級碳，合成出多種halichrome A衍生物。接著嘗試將C2-無取代的吲哚酚直接進行α-芳基化反應，也成功的得到多個產物。最後也成功地將芳基吲哚酚進行烷基化，也是成功地建立一個含有芳烴官能基的四級碳。透過不同地合成路徑合成不同的halichrome A衍生物，希望可以開發更具生物活性且更具專一性的藥物，期許可以在新藥開發有所貢獻。

關鍵字

吲哚酚；鈀金屬催化； α-芳基化反應

並列摘要

This research mainly describes the optimization process and results of palladium-catalyzed α-arylation of indoxyl species. Indoxyl species was prepared by using commercially available indole-3-carboxaldehyde as a starting material. Then we used a base to promote the alkylation of indoxyl. A series of different alkyl substituted indoxyl compounds were successfully synthesized. In the palladium-catalyzed α-arylation of α-alkylindoxyl, we tested different combinations of bases, ligands, palladium sources and solvents. After many experiments, we found that the optimal reaction condition comprises Cs2CO3 as base, Pd(dba)2 (6 mol%), P(Ad)3 (8 mol %) as the catalysts, THF and 1,4-dioxane as a co-solvent. We did α-arylation of α-alkylindoxyl that utilized a variety of different bromides, containing electron-donating group, electron-drawing group, and heteroatom, etc. We built a quaternary carbon containing an aryl group and synthesized a variety of halichrome A derivatives. Next, we tried to directly conduct the α-arylation reaction of C2-unsubstituted indoxyl, and accordingly a variety of products were obtained. Finally, the alkylation of aryl-indoxyl was also successfully carried out. We built a quaternary carbon containing an aryl group in different pathway. We would like to develop more bioactive and more specific drugs. And we hope to contribute to the development of new drugs.