Design, synthesis and evaluation in enantioselective catalysis of diverse adjustable axially chiral biphenyl ligands and catalysts

Chiral compounds widely occur in biomolecules, natural products and drugs, and acquisition of chirality in the chiral molecules highly depends on chiral inducers including chiral ligands and chiral catalysts in asymmetric chemical synthesis. Therefore, development of highly efficient and practical chiral ligands and catalysts is an eternal theme in chemical field. In the past decades, various axially chiral biaryldiol ligands and catalysts have been developed, in which the typical axially chiral cores should be [1,1'-naphenyl]-2,2'-diol (BINOL) and 1,1'-spirobiindane-7,7'-diol (SPINOL). It is known to all that the catalytic reactivity and enantioselectivity are generally substrate-dependent, and the slight variations in steric, electronic and geometric properties of chiral ligands or catalysts can cause dramatic changes in reactivity of substrates and enantioselectivity of products, so no omnipotent ligand or catalyst has been found thus far. Here we report the design, synthesis and evaluation in enantioselective catalysis of a new kind of adjustable axially chiral biphenyl ligands and catalysts, in which six model reactions including asymmetric additions of diethylzinc or alkynes to aldehydes in the presence of axially chiral [1,1'-biphenyl]-2,2'-diol ligands, Pd-catalyzed asymmetric cycloadditions in the presence of phosphoramidite ligands, and chiral phosphoric acid-catalyzed asymmetric synthesis of 1,1'-spirobiindane-7,7'-diol (SPINOL) derivative and [4+3] cyclization were attempted. The results showed that variation of 2,2'-substituent groups could provide different types of ligands and catalysts, and adjustment of substituent groups at the 3, 3', 5, 5', 6, 6'-positions could make ligands and catalysts more efficient in the asymmetric catalytic synthesis. Therefore, our present researches should provide a new and useful strategy for development of diverse axially chiral ligands and catalysts.