Thermodynamic Resolution of Pharmaceutical Precursor Modafinil Acid on the Basis of Chiral-at-Metal Strategy

Chiral-at-metal strategy was developed to resolve the essential sulfoxide pharmaceutical intermediates R-modafinil acid and its ana-logues with high yields and ee values.The efficient resolution process was achieved based on the diastereoselective discrimination caused by hydrogen bond and intramolecular π-π interaction between chiral-at-metal center and the coordinated chiral sulfoxide ligands.Moreover,the chiral Ir(lll)receptor can be reused with complete retention of their configurations and without the loss of reaction activity and enantioselectivity.This work provides a new access to synthesize R-modafinil acid as well as its analogues and develops the application of chiral-at-metal strategy in chiral resolution.

Enantioconvergent photoredox radical-radical coupling catalyzed by a chiral-at-rhodium complex

Racemicα-chloro imidazol-2-yl-ketones undergo an enantioconvergent photoactivated C–C bond formation with N-aryl glycines catalyzed by a single bis-cyclometalated chiral-at-rhodium catalyst in yields of up to 80%and up to 98%enantiomeric excess(ee).Control experiments support a mechanism which is initiated by a single electron transfer from N-aryl glycinate to the photochemically excited rhodium-boundα-chloro imidazol-2-yl-ketone,followed by chloride fragmentation of theα-chloroketone,decarboxylation of the glycinate,and a subsequent highly stereocontrolled radical-radical coupling.This work showcases the ability of the chiral rhodium catalyst to serve a dual function as chiral Lewis acid and at the same time as the photoredox active species upon substrate binding.

Catalytic enantioselective synthesis of β-amino alcohols by nitrene insertion

Chiral β-amino alcohols are important building blocks for the synthesis of drugs, natural products, chiral auxiliaries, chiral ligands and chiral organocatalysts. The catalytic asymmetric β-amination of alcohols offers a direct strategy to access this class of molecules. Herein, we report a general intramolecular C(sp^(3))–H nitrene insertion method for the synthesis of chiral oxazolidin-2-ones as precursors of chiral β-amino alcohols. Specifically, the ring-closing C(sp^(3))–H amination of N-benzoyloxycarbamates with 2 mol% of a chiral ruthenium catalyst provides cyclic carbamates in up to 99% yield and with up to 99% ee.The method is applicable to benzylic, allylic, and propargylic C–H bonds and can even be applied to completely non-activated C(sp^(3))–H bonds, although with somewhat reduced yields and stereoselectivities. The obtained cyclic carbamates can subsequently be hydrolyzed to obtain chiral β-amino alcohols. The method is very practical as the catalyst can be easily synthesized on a gram scale and can be recycled after the reaction for further use. The synthetic value of the new method is demonstrated with the asymmetric synthesis of a chiral oxazolidin-2-one as intermediate for the synthesis of the natural product aurantioclavine and chiral β-amino alcohols that are intermediates for the synthesis of chiral amino acids, indane-derived chiral Box-ligands, and the natural products dihydrohamacanthin A and dragmacidin A.

Rhodium（lll）/Amine Synergistically Catalyzed Enantioselective Alkylation of Aldehydes with α,β-Unsaturated 2-Acyl Imidazoles

A synergistic catalysis combination of chiral-at-metal rhodium complex and amine catalyst was developed for enantioselective alkylation of aldehydes with α,β-unsaturated 2-acyl imidazoles. The corresponding adducts were obtained in good yields with excellent enantioselectivities （up to 99% ee）.