Rearrangements and Intramolecular Diels−Alder Reactions of Normal and Vinylogous Aza-Morita−Baylis−Hillman Products Leading to Isoindoline Derivatives

Aza-Morita−Baylis−Hillman (aza-MBH) products derived from arylimines and methyl acrylate or acrylonitrile were N-alkylated with (E)-5-bromopenta-1,3-diene, and the resulting trienes were subjected to intramolecular Diels−Alder (IMDA) cyloadditions to afford the corresponding trans- and cis-fused tetrahydroisoindolines as the major and minor products, respectively. Catalysis with boron trichloride improved the IMDA diastereoselectivities of the nitrile derivatives, while yields were improved in both the nitrile and ester series. Treatment of the nitrile-substituted trienes with DABCO in DMF resulted in unexpected transposition of the N-(pentadienyl)sulfonamide group to the β-position of the acrylonitrile moiety. Subsequent IMDA cycloadditions produced cis-fused positional isomers of the previous tetrahydroisoindolines. When the products of vinylogous aza-MBH reactions in the nitrile series were N-propargylated, the resulting dienynes underwent a similar transposition and IMDA reaction, producing trans and cis diastereomers of the corresponding dihydroisoindolines as the major and minor products, respectively. In all but one case, only the former products were observed in the presence of methylaluminum dichloride, while the corresponding aromatized isoindolines were obtained when the IMDA reactions were carried out in the presence of DDQ. Thus, a variety of aryl-substituted isoindoline products with different levels of unsaturation and complementary substitution patterns and stereochemistry are readily available through these processes.