Design and Synthesis of Chiral Macrocycles Consisting of Azobenzene Units That Undergo Asymmetric Photochemical and Thermal Isomerization

It is well known that azobenzene undergoes reversible isomerization between ( E )- and ( Z )-forms upon irradiation with ultraviolet (UV) and visible light. This phenomenon has been extensively explored for its potential utility in photoresponsive systems and molecular machines. However, there are only a few examples of azobenzene-based systems that undergo asymmetric isomerization reactions between ( E )- and ( Z )-forms under photochemical and thermal conditions. Herein, we report the design and synthesis of 24-, 25-, and 26-membered chiral macrocycles ( R, R, R, R )- 12a – c and ( S, S, S, S )- 12a, consisting of azobenzene moieties and optically pure (1 R,2 R )- or (1 S,2 S )-1,2-diaminocyclohexane (DAC) units. We hypothesized that the ( Z )-forms of the azobenzene units would be stabilized due to the rigid macrocyclic structures, and that the chiral DAC units could be used to control the chirality of the isomerization reactions. The synthesis was conducted via cyclization reactions of the ( Z )-form intermediates produced by the photoirradiation of their ( E )-form intermediates. The photochemical and thermal behaviors of these macrocycles in solution were studied via 1 H NMR, UV–vis absorption spectra, circular dichroism (CD) spectra, and TD-DFT calculations. This study shows that 24-membered ( R, R, R, R )- 12a (and ( S, S, S, S )- 12a ) exclusively exist in the triangle-shaped ( Z )-( P )-form, and its ( E )-form was not observed even upon photoirradiation. The ( Z )-forms of ( R, R, R, R )- 12b and 12c were also found to be more stable than the ( E )-forms. These ( Z )-forms isomerize to their ( E )-forms, which are assumed to adopt arch bridge-shaped structures by TD-DFT calculations, upon irradiation with visible light, and ( E )-forms of 12b and 12c thermally isomerize back to ( Z )-forms at room temperature without photoirradiation. The results of this study represent prototypes for molecular machines that are able to undergo photochemical and thermal isomerization reactions between ( E )- and ( Z )-forms in an asymmetric manner.