Catalytic Asymmetric Synthesis of Unnatural Axially Chiral Biaryl δ-Amino Acid Derivatives via a Chiral Phenanthroline-Potassium Catalyst-Enabled Dynamic Kinetic Resolution.

Axially chiral biaryl δ-amino acids possess significantly different conformational properties and chiral environment from centrally chiral amino acids, therefore, have drawn considerable attention in the fields of synthetic and medicinal chemistry. Herein, a novel chiral phenanthroline-potassium catalyst has been developed by constructing a well-organized axially chiral ligand composed of one 1,10-phenanthroline unit and two axially chiral 1,1'-bi-2-naphthol (BINOL) units. In the presence of this catalyst, good to excellent yields and enantioselectivities (up to 99% yield, 98:2 er) have been achieved in the ring-opening alcoholytic dynamic kinetic resolution of a variety of biaryl lactams, thereby providing an efficient protocol for catalytic asymmetric synthesis of unnatural axially chiral biaryl δ-amino acid derivatives.

Axially Chiral N,N-Ligand-Promoted Pd-Catalyzed Enantioselective Allylic Amination and Alkylation.

An axially chiral N,N-ligand developed from a [1,1'-binaphthalene]-2,2'-diol (BINOL)-based skeleton and phenanthroline is found to be capable of promoting Pd-catalyzed asymmetric allylic amination and alkylation of allyl acetates. The reaction is compatible with cyclic and acyclic secondary amines, primary aliphatic amines, malononitrile, and dialkyl malonates, affording the corresponding chiral products in up to 99% yield and with up to >99% enantiomeric excess.

Novel Axially Chiral Ligand-Enabled Copper-Catalyzed Asymmetric Oxidative Coupling of 2-Naphthols for the Synthesis of 6,6'-Disubstituted BINOLs.

Novel axially chiral ligands have been designed and synthesized by merging the chelating picolinic acid with substituted BINOLs. The in-situ-prepared copper catalysts from the ligands and CuI enable the asymmetric oxidative coupling of 2-naphthols, affording 6,6'-disubstituted BINOLs in up to 89% yield with good enantioselectivities (up to 96:4 e.r.).

Conformational enantiodiscrimination for asymmetric construction of atropisomers.

Molecular conformations induced by the rotation about single bonds play a crucial role in chemical transformations. Revealing the relationship between the conformations of chiral catalysts and the enantiodiscrimination is a formidable challenge due to the great difficulty in isolating the conformers. Herein, we report a chiral catalytic system composed of an achiral catalytically active unit and an axially chiral 1,1'-bi-2-naphthol (BINOL) unit which are connected via a C-O single bond. The two conformers of the catalyst induced by the rotation about the C-O bond, are determined via single-crystal X-ray diffraction and found to respectively lead to the formation of highly important axially chiral 1,1'-binaphthyl-2,2'-diamine (BINAM) and 2-amino-2'-hydroxy-1,1'-binaphthyl (NOBIN) derivatives in high yields (up to 98%), with excellent enantioselectivities (up to 98:2 e.r.) and opposite absolute configurations. The results highlight the importance of conformational dynamics of chiral catalysts in asymmetric catalysis.