Pd-Catalyzed C-O Bond Formation Enabling the Synthesis of Congested N , N , O -Trisubstituted Hydroxylamines.

A Pd-catalyzed C-O cross-coupling of O -acyl hydroxylamines and tertiary or secondary alkyl electrophiles was reported without the cleavage of the rather fragile N-O bond. The described strategy provides direct access to congested N , N , O -trisubstituted hydroxylamines bearing an α-quaternary carbon center under mild conditions in high yields and features exclusively chemoselective C-O bond formation, a broad substrate scope, and excellent functional group tolerance. The synthetic potential of the cross-coupling was established via pharmaceuticals derivatizations and a series of postcatalytic modifications.