Department of Chemistry, Indian Institute of Science Education and Research (IISER), Bhopal MP-462 023, India.
J Org Chem. 2013 Aug 16;78(16):7823-44. doi: 10.1021/jo400890k. Epub 2013 Aug 8.
A methodology involving a "transition metal-free" intramolecular biaryl-coupling of o-halo-N-arylbenzylamines has been developed in the presence of potassium tert-butoxide and an organic molecule as catalyst. The reaction appears to proceed through KO(t)Bu-promoted intramolecular homolytic aromatic substitution (HAS). Interestingly, this biaryl coupling also works in the presence of potassium tert-butoxide as sole promoter. On extending our approach further, we found that N-acyl 2-bromo-N-arylbenzylamines undergo a one-pot N-deprotection/biaryl coupling followed by oxidation, thus offering an expeditious route to the phenanthridine and benzo[c]phenanthridine skeletons. The strategy has been applied to a concise synthesis of Amaryllidaceae alkaloids viz. oxoassoanine (1b), anhydrolycorinone (1d), 5,6-dihydrobicolorine (2d), trispheridine (2b), and benzo[c]phenanthridines alkaloids dihydronitidine (3b), dihydrochelerythidine (3d), dihydroavicine (3f), nornitidine (3h), and norchelerythrine (3j).
一种涉及邻卤-N-芳基苄基胺的“无过渡金属”分子内联芳耦合的方法已经在叔丁醇钾和有机分子作为催化剂的存在下得到了发展。该反应似乎通过 KO(t)Bu 促进的分子内均裂芳香取代（HAS）进行。有趣的是，这种联芳偶联反应在叔丁醇钾作为唯一促进剂的存在下也能进行。在进一步扩展我们的方法时，我们发现 N-酰基 2-溴-N-芳基苄基胺经历了一锅 N 脱保护/联芳偶联反应，随后进行氧化，从而提供了一种快速合成菲啶和苯并[c]菲啶骨架的方法。该策略已应用于简洁合成石蒜科生物碱，如奥沙酸（1b）、脱水石蒜碱（1d）、5,6-二氢比色林（2d）、三苯并环辛啶（2b）以及苯并[c]菲啶生物碱二氢尼替丁（3b）、二氢石蒜碱（3d）、二氢阿维啶（3f）、去甲尼替丁（3h）和去甲石蒜碱（3j）。
