N-杂环卡宾钯催化C-H活化构建咪唑并[1,2-a]吡啶的芳基化研究
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摘要
为了促进咪唑并[1,2-a]吡啶芳基化的高效偶联反应,本文设计了一种大位阻的Pd-PEPPSI催化剂用于催化直接C-H活化芳基化反应。论文探讨了卡宾配体对位阻的反应影响。在优化反应条件的基础上,钯配合物C2能够在0.1～0.05 mol%时高效合成一系列目标产物。
On the basis of development highly efficient protocol for Pd-catalyzed direct C-H cross-coupling reactions, bulky bis(imino)acenaphthene(BIAN)-supported Pd-PEPPSI complexes was applied in the arylation of imidazo[1,2-a]pyridine. The effect of N-moieties on NHCs was evaluated, and the cross coupling reaction conditions were screened. It revealed that the bulky Pd-PEPPSI complexe of C2 could be successfully employedin the coupling of aryl bromides at a lowpalladium loading of 0.1～0.05 mol %.
On the basis of development highly efficient protocol for Pd-catalyzed direct C-H cross-coupling reactions, bulky bis(imino)acenaphthene(BIAN)-supported Pd-PEPPSI complexes was applied in the arylation of imidazo[1,2-a]pyridine. The effect of N-moieties on NHCs was evaluated, and the cross coupling reaction conditions were screened. It revealed that the bulky Pd-PEPPSI complexe of C2 could be successfully employedin the coupling of aryl bromides at a lowpalladium loading of 0.1～0.05 mol %.
引文
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[7]Gorelsky S I.Origins of regioselectivity of the palladium-catalyzed(aromatic)C-H bond metalation-deprotonation.Coord Chem Rev,2013,257:153-164.
[8]He X X,Li Y F,Huang J,et al.A convenient phosphine-free palladium-catalyzed direct arylation of thiazole under mild aerobic conditions.J Organomet Chem,2016,803:58-66.
[9]Luo B T,Liu H,Lin Z J,et al.Aerobic and efficient direct arylation of five-membered heteroarenes and their benzocondensed derivatives with aryl Bromides by bulkyα-hydroxyimine palladium complexes.Organometallics,2015,34:4881-4894.
[10]Ouyang J S,Li Y F,Shen D S,et al.Bulkyα-diimine palladium complexes:highly efficient for direct C-H bond arylation of heteroarenes under aerobic conditions.Dalton Trans,2016,45:14919-14927.下转第页
[11]Chen F M,Lu D D,Hu L Q,et al.Camphyl-basedα-diimine palladium complexes:highly efficient precatalysts for direct arylation of thiazoles in open-air.Org Biomol Chem,2017,15:5731-5736.
[12]He X X,Li Y,Ma B B,et al.Sterically encumbered tetraarylimidazoliumcarbenePd-PEPPSI complexes:highly efficient direct arylation of imidazoles with aryl bromides under aerobic conditions.Organometallics,2016,35:2655-2663.
[2]Byth K F,Culshaw J D,Green S,et al.Imidazo[1,2-α]pyridines.Part 2:SAR and optimisation of a potent and selectiveclass of cyclin-dependent kinase inhibitors.Bioorg Med Chem Lett,2004,14:2245-2248.
[3]Emmitte K A,Wilson B J,Baum E W,et al.Discovery andoptimization of imidazo[1,2-α]pyridine inhibitors of insulin-like growth factor-1receptor(IGF-1R).Bioorg Med Chem Lett,2009,19:1004-1008.
[4]Hayakawa M,Kaizawa H,Kawaguchi K,et al.Synthesisand biological evaluation of imidazo[1,2-α]pyridine derivatives as novel PI3 kinasep110alpha inhibitors.Bioorg Med Chem,2007,15:403-412.
[5]Bellina F,Rossi R.Regioselective functionalization of the imidazole ring via transition metal-catalyzed C-N and C-C bond forming reactions.Adv Synth Catal,2010,352:1223-1276.
[6]Zhao D,You J,Hu C.Recent progress in coupling of two heteroarenes.Chem Eur J,2011,17:5466-5492.
[7]Gorelsky S I.Origins of regioselectivity of the palladium-catalyzed(aromatic)C-H bond metalation-deprotonation.Coord Chem Rev,2013,257:153-164.
[8]He X X,Li Y F,Huang J,et al.A convenient phosphine-free palladium-catalyzed direct arylation of thiazole under mild aerobic conditions.J Organomet Chem,2016,803:58-66.
[9]Luo B T,Liu H,Lin Z J,et al.Aerobic and efficient direct arylation of five-membered heteroarenes and their benzocondensed derivatives with aryl Bromides by bulkyα-hydroxyimine palladium complexes.Organometallics,2015,34:4881-4894.
[10]Ouyang J S,Li Y F,Shen D S,et al.Bulkyα-diimine palladium complexes:highly efficient for direct C-H bond arylation of heteroarenes under aerobic conditions.Dalton Trans,2016,45:14919-14927.下转第页
[11]Chen F M,Lu D D,Hu L Q,et al.Camphyl-basedα-diimine palladium complexes:highly efficient precatalysts for direct arylation of thiazoles in open-air.Org Biomol Chem,2017,15:5731-5736.
[12]He X X,Li Y,Ma B B,et al.Sterically encumbered tetraarylimidazoliumcarbenePd-PEPPSI complexes:highly efficient direct arylation of imidazoles with aryl bromides under aerobic conditions.Organometallics,2016,35:2655-2663.