Search

Thienylallylamines, readily accessible from the corresponding thienyl aldehydes, react with maleic and trifluoromethylmaleic anhydrides leading to the formation of acids with a thieno[2,3- f ]isoindole core. The reaction sequence involves two successive steps: acylation of the nitrogen atom of the initial allylamine and the intramolecular Diels-Alder vinylarene (IMDAV) reaction. The scope and limitations of the proposed method were thoroughly investigated. It has been revealed with the aid of X-ray analysis and DFT calculations that the key step, the IMDAV reaction, proceeds through an exo -transition state, giving rise to the exclusive formation of a single diastereomer of the target heterocycle. The obtained functionally substituted thieno[2,3- f ]isoindole carboxylic acids are potentially useful substrates for further transformations and bioscreening. The antimicrobial evaluation of the obtained compounds revealed that 1-oxo-2-(3-(trifluoromethyl)phenyl)hexahydrobenzo[4,5]thieno[2,3- f ]isoindole-10-carboxylic acid is the most active sample in the synthesized library. It exhibits antibacterial activity against sensitive strains of Gram-positive bacteria, including S. aureus , Enterococcus faecium , Bacillus cereus , and Micrococcus luteus , as well as the Gram-negative bacteria E. coli and Pseudomonas fluorescens , with MIC values ranging from 4 to 64 μg mL -1 . 9-Oxo-8-phenyloctahydronaphtho[2,1- d ]thieno[2,3- f ]isoindole-10-carboxylic acid showed antifungal activity against yeast culture C. albicans with a MIC value of 32 μM.

Diversely substituted, partially saturated benzo[ f ]isoindole-4-carboxylic acids were synthesized by a new three-component reaction (3CR) starting from cinnamic amines (3-arylallylamines), maleimides, and maleic anhydride. The process consists of N -acylation of the amines by maleic anhydride, intramolecular [4 + 2] cycloaddition in vinylarenes (the IMDAV reaction), and the concluding Alder-ene reaction between Diels-Alder intermediates and maleimides. All of the reaction steps proceed in a highly regio- and stereoselective manner, furnishing five adjacent chiral centers and leading to a single diastereoisomer of the title compound. The efficiency of the transformation is secured by thermal conditions or utilization of soft Lewis acids (Yb(OTf) 3 ) as catalysts. The kinetics and mechanism of the 3CR were studied by using dynamic 19 F NMR. Based on the NMR data and density functional theory (DFT) calculations, the IMDAV, not the Alder-ene, reaction is the rate-limiting step of the entire process.

The title compound, C 24 H 24 N 2 O 5 S, crystallizes with two independent mol-ecules ( A and B ) in the asymmetric unit. In the central ring systems of both mol-ecules, the tetra-hydro-furan rings adopt envelope conformations, the pyrrolidine rings adopt a twisted-envelope conformation and the six-membered ring is in a boat conformation. In mol-ecules A and B , the nine-membered groups attached to the central ring system are essentially planar (r.m.s. deviations of 0.002 and 0.003 Å, respectively). They form dihedral angles of 64.97 (9) and 56.06 (10)°, respectively, with the phenyl rings. In the crystal, strong inter-molecular O-H⋯O hydrogen bonds and weak inter-molecular C-H⋯O contacts link the mol-ecules, forming a three-dimensional network. In addition weak π-π stacking inter-actions [centroid-to centroid distance = 3.7124 (13) Å] between the pyrrolidine rings of the nine-membered groups of A mol-ecules are observed. Hirshfeld surface analysis and two-dimensional fingerprint plots were used to qu-antify the inter-molecular inter-actions present in the crystal, indicating that the environments of the two mol-ecules are very similar. The most important contributions for the crystal packing are from H⋯H (55.8% for mol-ecule A and 53.5% for mol-ecule B ), O⋯H/H⋯O (24.5% for mol-ecule A and 26.3% for mol-ecule B ) and C⋯H/H⋯C (12.6% for mol-ecule A and 15.7% for mol-ecule B ) inter-actions., (© Mertsalov et al. 2021.)

In the title compound, C 15 H 15 Br 2 NO 2 , two bridged tetra-hydro-furan rings adopt envelope conformations with the O atom as the flap. The pyrrolidine ring also adopts an envelope conformation with the spiro C atom as the flap. In the crystal, the mol-ecules are linked into dimers by pairs of C-H⋯O hydrogen bonds, thus generating R 2 2 (18) rings. The crystal packing is dominated by H⋯H, Br⋯H, H⋯π and Br⋯π inter-actions. One of the Br atoms is disordered over two sites with occupation ratio of 0.833 (8):0.167 (8)., (© Mertsalov et al. 2021.)

The title compounds C 24 H 21 NO 3 S, I , and C 24 H 21 NO 4 , II , are the products of the IMDAV reaction between phenyl-maleic anhydride and thien-yl(fur-yl)allyl-amines. Their mol-ecular structures comprise fused tricyclic systems containing thio-phene, cyclo-hexene and pyrrolidine rings ( I ) or furan, cyclo-hexene and pyrrolidine rings ( II ). The central cyclo-hexene and pyrrolidine rings in both compounds adopt slightly twisted boat and envelope conformations, respectively. The dihedral angles between the basal plane of the pyrrolidine ring and the thio-phene (in I ) or furan (in II ) ring plane are 22.74 (16) and 26.29 (5)°, respectively. The nitro-gen atom both in I and II has practically planar environment [the sums of the bond angles are 359.8 and 358.9°, respectively]. In the crystal of I , the mol-ecules form hydrogen-bonded zigzag chains along [010] through strong inter-molecular O-H⋯O hydrogen bonds involving carb-oxy-lic and keto groups, whereas in the crystal of II , the mol-ecules are joined into centrosymmetric dimers by strong O-H⋯O hydrogen bonds between the carb-oxy-lic groups. In II , the atoms involved into these hydrogen bonds (and hence the whole carb-oxy-lic group) are disordered over two sets of sites with an occupancy ratio of 0.6:0.4. Compounds I and II crystallize as racemates consisting of enanti-omeric pairs of the 3a SR ,4 RS ,4a RS ,7a SR and 3a SR ,4 SR ,4a RS ,7a SR diastereomers, respectively.