Progress Towards the Synthesis of Conformationally Controlled Planar Chiral Macrocyclic Metacyclophanes

Abstract

In recent years, planar chirality has been a topic of particular synthetic, catalytic, and pharmaceutical interest. One prominent challenge within the realm of planar chiral synthesis is controlling for particular conformations with respect to the molecules’ orientation in space as these different conformations, referred to as syn- and anti-, can interact with biological targets differently. Our group hypothesizes that we can control for the different conformations by changing the structure of the linking chains that join the two arenes. By changing the configuration of the alkenes on the linker chain, E vs. Z, we hypothesize that we can selectively synthesize the syn¬- and anti¬- products. We postulate the E alkene should favor the syn-product and the Z alkene should favor the anti-product. To test this, two [5.5]metacyclophane macrocyclization diol precursors that differ only in their alkene configuration will be synthesized and the subsequent macrocycles will be analyzed via X-Ray crystallography to identify their syn-/anti- conformation. After attempting other unsuccessful pathways, the current direction of the project aims to synthesize a vinyl bromide substrate with the desired E/Z configuration and cross couple that with a synthesized bis(bpinmethyl)benzene substrate in a Suzuki reaction to obtain the desired substrates for macrocyclization.