Cobalt/Salox‐Catalyzed Enantioselective Dehydrogenative C−H Alkoxylation and Amination

Abstract

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.

Enantioselective cobaltaelectro-catalyzed C–H activations enabled by hydrogen evolution

“…1B). (22)(23)(24)(25) In sharp contrast, the use of Earth-abundant 3d transition metals (26)(27)(28)(29)(30)(31)(32)(33)(34) in enantioselective electrocatalytic C-H activation has thus far unfortunately proven elusive. Given these major restrictions, we questioned whether enantioselective electrocatalytic C-H activation could be accomplished with 3d transition metal catalysts which typically proceed via single electron transfer (SET) elementary steps.…”

Electrochemical C−H/C−C Bond Oxygenation: A Potential Technology for Plastic Depolymerization

“…As sacrificial oxidants, vast quantities of silver salts were utilized, leading to significant costs and harmful consequences. [226] The first electrochemical enantioselective CÀ H oxygenation catalyzed by Co II in order to resolve this flaw was described. [227][228][229][230][231][232][233][234][235] The use of electricity in place of stoichiometric silver salts, which only produces H 2 as a byproduct, good yields and excellent enantioselectivities (up to 98 % yield and > 99 % ee), the isolation and complete characterization of cobalt(III) alcohol complex, which was discovered to be a crucial intermediate in this CÀ H alkoxylation process, are some main benefits of this strategy.…”

“…For the electrochemical enantioselective method, a reasonable catalytic cycle was suggested (scheme 41), based on our mechanistic research and precedents. [220,226,[236][237][238] The chiral octahedral Co III complex A was initially produced by the anodic oxidation of Co II in the presence of Salox ligand and NaOPiv. Cobaltacycle intermediate B coordinated with alcohol was produced by a subsequent ligand exchange with phosphinamide 58, followed by an enantio-determining, carboxylate-assisted CÀ H activation.…”

“…As sacrificial oxidants, vast quantities of silver salts were utilized, leading to significant costs and harmful consequences [226] . The first electrochemical enantioselective C−H oxygenation catalyzed by Co II in order to resolve this flaw was described [227–235] .…”

“…For the electrochemical enantioselective method, a reasonable catalytic cycle was suggested (scheme 41), based on our mechanistic research and precedents [220,226,236–238] . The chiral octahedral Co III complex A was initially produced by the anodic oxidation of Co II in the presence of Salox ligand and NaOPiv.…”