Synthesis of the planar chiral [2.2]paracyclophane based bis(benzoxazole) ligands and applications in asymmetric mukaiyama aldol reaction

Planar chiral ligands play an important role in asymmetric synthesis. Recently, [2.2]paracyclophane attracts considerable attention as a planar chiral backbone and serves as a powerful tool to develop new and efficient ligands for the asymmetric synthesis. The aim of this study is to synthesize a novel planar chiral bis(benzoxazole) ligands based on the [2.2]paracyclophane backbone and test their activity in asymmetric Mukaiyama aldol reactions. In the first stage of this study, ortho- substituted planar chiral amino phenol derivatives were prepared starting from [2.2]paracyclophane. In the second stage, planar chiral bis(benzoxazole) ligands containing pyridin or methylene moieties were synthesized in two steps by coupling the corresponding acyl chloride and amino phenol followed by intramolecular ring closure with methanesulfonic acid. Then the synthesized planar chiral bis(benzoxazole) ligands ((Sp,Sp)-133 and (Sp,Sp)-136) were tested in asymmetric Mukaiyama–aldol reaction of a variety of aldehydes with silyl enol ethers as a metal-base Lewis acid catalyst. The present study provides a concept for the design and synthesis of new type of planar chiral bis(benzoxazole) ligands and in this study, to the best of our knowledge, the first planar chiral Box and Pybox type ligands were introduced to the literature. Unfortunately, although the synthesis is carried out with a 100% enantiomeric excess, no selectivity was observed in the asymmetric Mukaiyama-aldol reaction with these novel type bis(benzoxazole) ligands ((Sp,Sp)-133 and (Sp,Sp)-136). But, these new chiral ligands can be used for many different asymmetric reactions.