Diastereoselective Cycloadditions and Transformations of <i>N</i>-Alkyl and <i>N</i>-Aryl Maleimides with Chiral 9-Anthrylethanol Derivatives

Thermal Diels−Alder reactions of chiral 9-methoxyethyl and 9-hydroxyethyl anthracene have been investigated both experimentally and computationally with a range of N-substituted maleimides. Whereas cycloadditions with 9-methoxyethyl anthracene proceeded with almost complete diastereselectivity, those with 1-anthracene-9-yl-ethanol resulted in essentially no diastereoselectivity. Subsequent regio- and stereoselective transformations with reducing agents and carbon nucleophiles demonstrated the synthetic utility of this methodology, which was applied to the enantioselective synthesis of pyrrolo[2,1-a]isoquinolines and an attempted synthesis of the alkaloid crispine A. Computational studies supported the proposed hypotheses for the stereoselectivity observed in the transformations described.本研究针对手性9-甲氧基乙基蒽（chiral 9-methoxyethyl anthracene）与9-羟乙基蒽（9-hydroxyethyl anthracene）和一系列N-取代马来酰亚胺（N-substituted maleimides）的热诱导狄尔斯-阿尔德反应（Thermal Diels−Alder reactions），通过实验与计算两种手段开展了系统性探究。相较之下，9-甲氧基乙基蒽参与的环加成反应几乎完全呈现非对映选择性，而1-(蒽-9-基)乙醇参与的反应则几乎未表现出非对映选择性。后续借助还原剂与碳亲核试剂（carbon nucleophiles）开展的区域及立体选择性转化实验，验证了该方法学的合成应用价值；研究团队将此方法应用于吡咯并[2,1-a]异喹啉（pyrrolo[2,1-a]isoquinolines）的对映选择性合成，并开展了生物碱crispine A的合成尝试。计算研究为上述转化过程中观测到的立体选择性现象的相关假设提供了理论支撑。