Atropisomeric anilides have received tremendous attention as a novel class of chiral compounds possessing restricted rotation around an N-aryl chiral axis. However, in sharp contrast to the well-studied synthesis of biaryl atropisomers, the catalytic asymmetric synthesis of chiral anilides remains a daunting challenge, largely due to the higher degree of rotational freedom compared to their biaryl counterparts. Here we describe a highly efficient catalytic asymmetric synthesis of atropisomeric anilides via Pd(II)-catalyzed atroposelective C−H olefination using readily available L-pyroglutamic acid as a chiral ligand. A broad range of atropisomeric anilides were prepared in high yields (up to 99% yield) and excellent stereoinduction (up to >99% ee) under mild conditions. Experimental studies indicated that the atropostability of those anilide atropisomers toward racemization relies on both steric and electronic effects. Experimental and computational studies were conducted to elucidate the reaction mechanism and rate-determining step. DFT calculations revealed that the amino acid ligand distortion is responsible for the enantioselectivity in the C−H bond activation step. The potent applications of the anilide atropisomers as a new type of chiral ligand in Rh(III)-catalyzed asymmetric conjugate addition and Lewis base catalysts in enantioselective allylation of aldehydes have been demonstrated. This strategy could provide a straightforward route to access atropisomeric anilides, one of the most challenging types of axially chiral compounds.

The past decade has witnessed a rapid progress in asymmetric CÀ H activation. However, the enantioselective CÀ H alkoxylation and amination with alcohols and free amines remains elusive. Herein, we disclose the first enantioselective dehydrogenative CÀ H alkoxylation and amination enabled by a simple cobalt/ salicyloxazoline (Salox) catalysis. The use of cheap and readily available cobalt(II) salts as catalysts and Saloxs as chiral ligands provides an efficient method to access P-stereogenic compounds in excellent enantioselectivities (up to > 99 % ee). The practicality of this protocol is demonstrated by gram-scale preparation and further derivatizations of the resulting P-stereogenic phosphinamides, which offering a flexible asymmetric alternative to access P-stereogenic mono-and diphosphine chiral ligands. Preliminary mechanistic studies on the enantioselective CÀ H alkoxylation reaction suggest that a cobalt(III/IV/II) catalytic cycle might be involved.

The past decade has witnessed a rapid progress in asymmetric CÀ H activation. However, the enantioselective CÀ H alkoxylation and amination with alcohols and free amines remains elusive. Herein, we disclose the first enantioselective dehydrogenative CÀ H alkoxylation and amination enabled by a simple cobalt/ salicyloxazoline (Salox) catalysis. The use of cheap and readily available cobalt(II) salts as catalysts and Saloxs as chiral ligands provides an efficient method to access P-stereogenic compounds in excellent enantioselectivities (up to > 99 % ee). The practicality of this protocol is demonstrated by gram-scale preparation and further derivatizations of the resulting P-stereogenic phosphinamides, which offering a flexible asymmetric alternative to access P-stereogenic mono-and diphosphine chiral ligands. Preliminary mechanistic studies on the enantioselective CÀ H alkoxylation reaction suggest that a cobalt(III/IV/II) catalytic cycle might be involved.

The past decade has witnessed a rapid progress in asymmetric C–H activation. However, the enantioselective C–H alkoxylation and amination with alcohols and free amines remains elusive. Herein, we disclose the first enantioselective dehydrogenative C–H alkoxylation and amination enabled by a simple cobalt/salicyloxazoline (Salox) catalysis. The use of cheap and readily available cobalt(II) salts as catalysts and Saloxs as chiral ligands provides an efficient method to access P-stereogenic compounds in excellent enantioselectivities (up to >99% ee). The practicality of this protocol is demonstrated by gram-scale preparation and further derivatizations of the resulting P-stereogenic phosphinamides, which offering a flexible asymmetric alternative to access P-stereogenic mono- and diphosphine chiral ligands. Preliminary mechanistic studies on the enantioselective C–H alkoxylation reaction suggest that a cobalt(III/IV/II) catalytic cycle might be involved.