3-(Hetero)aryl-4-indolylamino-α-tetralones by Diastereoselective Internal Redox Cyclization: An “Azaenamine” Conjugate Addition

(E)-3-(Hetero)aryl-1-(2-((E)-(indolin-1-ylimino)methyl)phenyl)prop-2-en-1-ones 1 undergo 6-exo-trig cyclization reactions upon treatment with BF3·Me2S in dichloromethane at low temperature to give the tetralones 10 in good yield. This cyclization process can be considered to be an intramolecular Michael-type addition which is accompanied by an internal redox reaction as the indoline fragment is oxidized to indole with simultaneous hydrogen shift to nitrogen atom N1 and the α-carbon atom of the Michael system. The reactions at the iminic centers take place via umpolung of the classical carbonyl reactivity. The reaction is diastereoselective and affords exclusivly 3,4-disubstituted α-tetralones 10 as trans-diastereomers. According to quantum chemical calculations the reactions take place under kinetic control with the trans-diastereomer being the kinetically favored product as it has the lower activation barrier compared to the cis-diastereomer.

(E)-3-(杂芳基)芳基-1-(2-((E)-(吲哚啉-1-基亚氨基)甲基)苯基)丙-2-烯-1-酮（(E)-3-(Hetero)aryl-1-(2-((E)-(indolin-1-ylimino)methyl)phenyl)prop-2-en-1-ones）1，在低温下以二氯甲烷（dichloromethane）为反应溶剂、三氟化硼·二甲硫醚络合物（BF3·Me2S）作为试剂处理时，会发生6-exo-trig环化反应，以良好收率得到四氢萘酮（tetralones）10。该环化过程可被视为分子内迈克尔型加成（intramolecular Michael-type addition）反应，伴随分子内氧化还原过程：吲哚啉（indoline）片段被氧化为吲哚（indole），同时发生氢原子迁移至氮原子N1以及迈克尔体系的α-碳原子上。亚胺中心的反应经由经典羰基反应性的极性反转（umpolung）路径进行。该反应具有非对映选择性，仅专一性生成反式非对映异构体（trans-diastereomers）形式的3,4-二取代α-四氢萘酮10。根据量子化学计算（quantum chemical calculations）结果，该反应受动力学控制（kinetic control），反式非对映异构体为动力学优势产物，因其相较于顺式非对映异构体（cis-diastereomer）具有更低的活化能垒（activation barrier）。