Dipyridyl/pyridinium thieno[2,3- b]thiophenes as new atropisomeric systems. Synthesis, conformational analysis and energy minimization

• Published in: Tetrahedron 2005-04, Vol.61 (14), p.3507-3513
• Main Authors: Mashraqui, Sabir H., Sangvikar, Yogesh, Ashraf, Mohamed, Kumar, Sukeerthi, Dâub, Elise Trân Huu
• Format: Article
• Language: English
• Subjects: Atropisomers; Conformational analysis; Dynamic 1H NMR; Energy minimization; peri-Dipyridylthienothiophenes; Synthesis
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2005.01.123

Synthesis of a new class of cofacially oriented dipyridyl(pyridinium)lthieno[2,3- b]thiophenes with or without –CO 2Et and –COMe substituents at C2, and C5 positions of thieno[2,3- b]thiophene ring was readily accomplished using a double Dieckman cyclization protocol as the key step. While C2/C5 substituted dipyridylthieno[2,3- b]thiophenes exhibited syn/ anti atropisomerism at least up to 70 °C with Arrhenius energy of activation (Δ G ≠) in the range of 17–18 kcal/mol, on the other hand unsubstituted dipyridylthieno[2,3- b]thiophene and its bis- N-quaternized salt were found to show free conformational rotation with an estimated Δ G ≠ of lower than 10 kcal/mol. Conformational energy minimization using AM1 protocol revealed a slight preference for the anti over syn isomers. Compared to the unsubstituted dipyridylthieno[2,3- b]thiophenes, higher energy barriers to rotation (3.7–5.1 kcal/mol) in substituted dipyridylthieno[2,3- b]thiophenes can be attributed to steric encumbrance resulting from –CO 2Et and –COMe substituents located on the non-rotating thienothiophene platform. Dipyridylthieno[2,3- b]thiophenes 2a and 2b exhibit syn/ anti atropisomerism with energy barrier to rotation Δ G ≠ in the range of 17–18 kcal/mol, whereas 2c and 2d exhibit free rotation at least up to −50 °C with Δ G ≠≤10 kcal/mol.