Department of Applied Chemistry, National Chiao Tung University, Hsinchu 300-10, Taiwan.
Chem Asian J. 2011 Jun 6;6(6):1557-65. doi: 10.1002/asia.201000913. Epub 2011 Apr 5.
A novel strategy for an unconventional Pictet-Spengler reaction has been developed for the regioselective cyclization of the imidazole ring system at the C2 position. The developed strategy was utilized to develop a diversity-oriented parallel synthesis for bis(heterocyclic) skeletal novel analogs of benzimidazole-linked imidazoquinoxalines on a soluble polymer support under microwave conditions. Condensation of polymer-immobilized o-phenylenediamines with 4-fluoro-3-nitrobenzoic acid followed by nucleophilic aromatic substitution with an imidazole motif affords bis(heterocyclic) skeletal precursors for the Pictet-Spengler reaction. The unconventional Pictet-Spengler cyclization with various aldehydes was achieved regioselectively at the C2 position of the imidazole ring to furnish rare imidazole-fused quinoxaline skeletons. During the Pictet-Spengler cyclization, aldehydes bearing electron-donating groups afford 4,5-dihydro-imidazoquinoxalines, which then auto-aromatize into benzimidazole-linked imidazo[1,2-a]quinoxalines. However, interestingly, aldehydes bearing electron-withdrawing groups directly provide aromatized imidazo[1,2-a]quinoxalines, which unexpectedly afford novel benzimidazole-linked 4-methoxy-4,5-dihydro-imidazo[1,2-a]quinoxalines after polymer cleavage.
一种新颖的非传统 Pictet-Spengler 反应策略已被开发用于咪唑环系统在 C2 位置的区域选择性环化。该开发的策略被用于在微波条件下，在可溶性聚合物载体上进行双（杂环）骨架新颖的苯并咪唑连接的咪唑并喹喔啉的多样性导向平行合成。聚合物固定的邻苯二胺与 4-氟-3-硝基苯甲酸缩合，然后用咪唑基取代亲核芳香取代，得到用于 Pictet-Spengler 反应的双（杂环）骨架前体。非传统的 Pictet-Spengler 环化在咪唑环的 C2 位置区域选择性地与各种醛反应，得到罕见的咪唑稠合喹喔啉骨架。在 Pictet-Spengler 环化过程中，带有供电子基团的醛提供 4,5-二氢-咪唑并喹喔啉，然后自动芳构化为苯并咪唑连接的咪唑并[1,2-a]喹喔啉。然而，有趣的是，带有吸电子基团的醛直接提供芳构化的咪唑并[1,2-a]喹喔啉，这些喹喔啉在聚合物裂解后出乎意料地提供新颖的苯并咪唑连接的 4-甲氧基-4,5-二氢-咪唑并[1,2-a]喹喔啉。
