I. Reactivity of electron deficient indoles toward nucleophiles, Diels-Alder reactions and dipolar cycloadditions. II. Synthesis of pyrrolo[3,4-b]indoles

Earlier in our laboratory, a facile synthesis of the 2- and 3-nitroindoles was realized. These compounds showed promise as powerful intermediates in the synthesis of novel structures and natural products. The reactivity of 2- and 3-nitroindoles towards nucleophilic additions, Diels-Alder reactions and dipolar cycloadditions was explored. The effect of the nitrogen substitution was also examined.; 1-(Phenylsulfonyl)-3-nitroindole undergoes nucleophilic addition by enolate anions to form 2-substituted 3-nitroindolines in moderate to good yield. Grignard reagents also add to 1-(phenylsulfonyl)-3-nitroindole to form indolines as the major product and indoxyls as the minor product. Aryl lithiums add to 1-(phenylsulfonyl)-3-nitroindole to form the 2-aryl-3-nitroindoles in moderate yields. tert-Butyl 3-nitroindole-1-carboxylate also undergoes nucleophilic addition by enolate anions and Grignard reagents.; Diels-Alder reactions between 2- and 3-nitroindoles with Danishefsky's diene produce the expected 3- and 2-hydroxycarbazoles in good yields, with complete regioselectivity. The cycloadditions between 2-nitroindoles and Rawal's diene result in the silyloxy protected hydroxycarbazole.; Dipolar cycloadditions between 2-and 3-nitroindoles and a variety of dipoles were examined. To date, the reaction between sydnones and thiomunchnones and nitroindoles has not been successful. The addition of an azomethine ylide to the 3-nitro-1-carboethoxyindole produces the cycloadduct 538, which contained the pyrrolo[3,4-b]indole ring system.; A facile synthesis of pyrrolo[3,4-b]indoles was developed from commercially available 2,3-dimethylindole. Protection and Wohl-Ziegler bromination produces the known 2,3-bis(bromomethyl)indole in 68% yield. This can be transformed into the dihydropyrroloindoles in good yields (61–74%) by treatment with a dilute solution of a primary amine, such as tert -butylamine and benzylamine. The dihydropyrroloindoles were oxidized with DDQ in high yields (85–98%). The dihydropyrroloindoles show promise as intermediates in a new route to indole-2,3-quinodimethanes.; Several approaches to the novel anti-tumor alkaloid, iheyamine, are presented, along with some preliminary work towards the necessary methodology for the total synthesis of this structure.