Synthesis, Conformational Properties and DFT Computational Studies of Polymethyl-Substituted [3.3]Metacyclophanes

Polymethyl substituted [3.3]metacyclophanes (MCPs) 4a-d, were synthesized by the TosMIC coupling method followed by Wolff-Kishner reduction of the corresponding polymethyl-substituted [3.3]MCP-2,11-diones (3a-d). (HNMR)-H-1 spectroscopy reveals that both 5,6,7,14,16-pentamethyl[3.3]MCP-2,11-diones (3a and 3b) undergo conformational changes relative to the NMR time scale in solution at room temperature but that the anti conformer is preferred. Reduced 5,6,7,14,16-pentamethyl[3.3]MCP (4a and 4b) adopt fixed syn-conformations in solution at room temperature. X-ray analysis showed that in the solid state, 5,6,7,14,15,16-hexamethyl[3.3]MCP-2,11-dione 3a adopts the anti-conformation and reduced 5,6,7,14,16-pentamethyl[3.3]MCP-2,11-diones 4b adopts a syn-(chair-chair) conformation. A series of electrophilic substitution reactions such as formylation, acetylation and nitration were carried out with 5,6,7,14,16-pentamethyl[3.3]MCP 4b to study their conformational isomers. The formyl, acetyl and nitro derivatives of 5,6,7,14,16-pentamethyl[3.3]MCP are fixed to adopt syn-conformations in solution at room temperature. The conformational isomers of the metacyclophanes and derivatives obtained from density functional theory (DFT) methods were used to estimate the total energies and energy minimized structures of the different conformations.