Synthesis of substituted asymmetrical biphenyl amino esters as alpha helix mimetics

As part of our ongoing project to develop new molecular probes for estrogen receptor-alpha, we are exploring the utility of internally-substituted asymmetric biphenyls as a proteomimetic scaffold. In this study, we describe synthetic methods for preparing the requisite substituted-bromophenol precursors, their further elaboration, and the subsequent Suzuki–Miyaura coupling of these sterically-hindered and electronically-rich aromatic systems. The results provide an efficient route with which to generate further libraries of novel asymmetric biphenyl compounds as potential proteomimetics.