We have developed tandem N-acylation – cycloaddition reactions that make it possible to construct isoindole derivatives annulated with thiophene, pyrrole, indole, and benzofuran fragments. Also methods for preparation of some iptycene, furo[2,3-c]pyrrolo-2,4-dione and phenanthridone derivatives have been disclosed. The developed synthetic methods are suitable for creating combinatorial libraries of compounds and for further studying their biological activity. 3- (2- Or 3-thienyl) allylamines were obtained, which were acylated at the amino group with maleic anhydride. It was found that under the same conditions, an intramolecular Diels-Alder reaction occurs. If the interaction between maleic anhydride and thienylalylamines was carried out at room temperature in diethyl ether or at 80°C in benzene, only products containing a non-aromatic thiophene ring were observed. Instead, in the case of the use of toluene as a solvent and providing synthesis at 110 ° C, the process did not stop at the Diels-Alder stage but was accompanied by prototropic tautomerism of the primary adducts into those containing an aromatic thiophene ring. The acylation of thienylalylamines with substituted α,β-unsaturated anhydrides is regioselective. The nucleophilic attack by a secondary nitrogen atom occurs at the most sterically available carbonyl group of substituted maleic anhydrides. Only non-aromatic adducts are formed at temperatures below 80°C. Instead, when the reaction temperature exceeded 100°C, selective formation of products with an aromatic thiophene ring was observed. It was found that the IMDAV reaction of thienylalylamines with 2,3-dichloromaleic anhydride is unusual. It proceeds with the elimination of only one molecule of hydrogen chloride and decarboxylation. Cinnamoyl and ethyl fumaroyl chlorides, being weaker dienophiles compared to maleic anhydrides, can also be involved in the tandem acylation/IMDA reaction with vinylthiophenes. The possibility of obtaining diastereomerically enriched (de up to 87%) thienoisoindolone with careful control of the reaction temperature is shown. We have studied pyrrole, indole, and benzofuran derivatives in IMDAV reactions. A method for preparing the starting compound N,N-dimethylaminoacrolein was developed. Indolopropenylamines interact with maleic anhydride and react in such a way that the amino group is first acylated, resulting in the formation of intermediates. This is followed by cycloaddition. Also, the allylamine moiety was introduced not in the β- but in the α-position to the nitrogen atom for pyrrole derivatives by the Wilsmeier acrylation reaction. The obtained pyrrolopropenylamines were tested in the intramolecular Diels-Alder reaction. The reaction goes well. The synthetic potential of benzofuran series dienes in the Diels-Alder intramolecular reaction was also disclosed. Which react with maleic anhydride to form benzofuro[2,3-f]-isoindole-10-carboxylic acid, with high yields. A convenient method, for preparation of a new class of N-substituted framework pyrrolidone-iptycene hetero systems has been developed. The cascade synthesis of tetrahydro-2H-furo[2,3-c]pyrrolo-2,4(3H)-dione derivatives, the key stage of which is retro-aldol condensation, was studied. Methods for the synthesis of phenanthridone derivatives have been developed.
