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 cyclo44 (OC-4), that can exist at 298 K as two stable atropisomers with C and C symmetry denoted as C-OC-4 and C-OC-4, respectively. Heating induces the efficient stepwise conversion of C- to C-OC-4 via a C-symmetric intermediate (C-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- and C-OC-4 from C-OC-4. In contrast to C-OC-4, C-OC-4 can bind linear guests to form pseudo-rotaxans, or bind C or C 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.