AMINO-CLAISEN REARRANGEMENTS OF N-VINYLISOQUINUCLIDENES IN NOVEL APPROACHES TO THE SYNTHESIS OF HYDROISOQUINOLINES AND HYDROPHENANTHRIDINES

Model studies probing novel and potentially efficient approaches to the synthesis of hydroisoquinolines and hydrophenanthridines are described. Synthetic designs investigated employ amino-Claisen and related rearrangement reactions to transform easily prepared N-vinylisoquinuclidenes to these nitrogen containing, fused bicyclic and tricyclic systems. One approach developed utilizes nucleophilic substitution reactions of N-methylated isoqui-nuclidenes with β-chloro-α,β-unsaturated ketones to generate the transient N-vinylated quaternary ammonium salts. Rearrangements of these substances occur at room temperature and produce the hydroisoquinolines 12, 13β, and 13α. This route fails when the (3-halo enone precursors possess alkyl substitution at the β carbon. However, an alternate and more versatile procedure was developed utilizing acid-catalyzed rearrangements of β-amino-α,β-unsaturated ketones 20, 22, and 24, derived from reactions of secondary isoquinuclidenes with β-chloro enones. The generality of this latter approach is demonstrated by its utility in preparation of hydrophenanthridines 21, 23, and 25 and phenanthridone 27. The mechanistic features, synthetic potential, and possible limitations of these rearrangement reactions are discussed. © 1979, American Chemical Society. All rights reserved.