Diastereoselective Cycloadditions and Transformations of N-Alkyl and N-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-anthracenc-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.