Controlled interconversion of macrocyclic atropisomers via defined intermediates.

Macrocyclic conformations play a crucial role in regulating their properties. Our understanding of the determinants to control macrocyclic conformation interconversion is still in its infancy. Here we present a macrocycle, octamethyl cyclo[4](1,3-(4,6)-dimethylbenzene)[4]((4,6-benzene)(1,3-dicarboxylate) (OC-4), that can exist at 298 K as two stable atropisomers with C_2v and C_4v symmetry denoted as C_2v-OC-4 and C_4v-OC-4, respectively. Heating induces the efficient stepwise conversion of C_2v- to C_4v-OC-4 via a C_s-symmetric intermediate (C_s-OC-4). It differs from the typical transition state-mediated processes of simple C–C single bond rotations. Hydrolysis and further esterification with a countercation dependence promote the generation of C_2v- and C_s-OC-4 from C_4v-OC-4. In contrast to C_2v-OC-4, C_4v-OC-4 can bind linear guests to form pseudo-rotaxans, or bind C₆₀ or C₇₀ efficiently. The present study highlights the differences in recognition behavior that can result from conformational interconversion, as well as providing insights into the basic parameters that govern coupled molecular rotations. The three-dimensional conformation of macrocycles determine their chemical and recognition properties and the factors that influence the interconversion between macrocyclic forms are poorly understood. Here the authors describe a macrocycle existing as two stable atropisomers and the mechanism behind the thermally-induced transition between them. [ABSTRACT FROM AUTHOR]