Development of Diverse Ligands and Catalysts Derived from Axially Chiral Cyclic Biphenyldiols

The development of suitable chiral ligands and catalysts is a key factor in asymmetric organic synthesis. In this paper, we describe the design, synthesis and evaluation of a new kind of adjustable axially chiral cyclic biphenyl ligands and catalysts derived from axially chiral cyclic biphenyldiols, and four representative examples were performed well including enantioselective alkynylation of benzo[e][1,2,3]oxathiazine 2,2-dioxide under catalysis of (R)-cyclic [1,1'-biphenyl]-2,2'-diol/ZnMe₂, palladium-catalyzed decarboxylative cycloaddition of 4-phenyl-4-vinyl-1,3-dioxolan-2-one with 2-arylidenemalononitriles in the presence of axially chiral cyclic phosphoramidite ligand, and axially chiral cyclic phosphoric acid-catalyzed asymmetric Diels-Alder cycloaddition of styryl-1H-indole with cyclic 2,4-dienones and asymmetric Michael addition of indolizine to cyclopentenediones. The experiments showed that variation of 2,2'-substituent groups could provide different kinds of axially chiral cyclic ligands and catalysts, variation of steric and electronic properties (by changing substituent groups at the 3,3',5,5'-positions) and dihedral angles (by changing ring sizes at 6,6'-positions) could greatly change catalytic efficiency of ligands and catalysts derived from axially chiral cyclic biphenyldiols. The high reactivity and stereoselectivity of the reactions were effectively achieved through the precise regulation of multi-sites on our axially chiral cyclic biphenyldiols.