Cobalt/Salox-Catalyzed Enantioselective Dehydrogenative C-H Alkoxylation and Amination

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.

Automated summary

The past decade has seen significant progress in asymmetric C-H activation, although achieving enantioselective C-H alkoxylation and amination with alcohols and free amines has remained challenging. In this study, we report the first enantioselective dehydrogenative C-H alkoxylation and amination using a simple cobalt/salicyloxazoline (Salox) catalyst. By using inexpensive cobalt(II) salts as catalysts and Saloxs as chiral ligands, we have developed an efficient method to access P-stereogenic compounds with excellent enantioselectivities (up to >99% ee). The practicality of this protocol has been demonstrated through gram-scale preparation and further derivatizations of the resulting P-stereogenic phosphinamides, offering a flexible asymmetric alternative to access P-stereogenic mono- and diphosphine chiral ligands. Preliminary mechanistic studies suggest the involvement of a cobalt(III/IV/II) catalytic cycle in the enantioselective C-H alkoxylation reaction.