Rhodium-Catalyzed Atroposelective Alkyne Oxyamidation Using Non-Nitrene NH Acyloxyamide Reagents

Oxyamination represents a fundamentally important transformation that simultaneously introduces two heteroatoms. Despite intensive studies of asymmetric oxyamination of olefins, oxyamination of alkynes has been largely untraversed and the asymmetric version remains untouched, which is attributed to poor interactions between alkynes and nitrenes/nitrogen radicals that would yield unstable alkenyl radicals/cations. Acyloxyamides are herein repurposed as bifunctional N, O-reagents toward atroposelective oxyamidation of sterically hindered alkynes. The coupling system accommodates two classes of acyloxyamides and two distinct categories of alkynes, affording tetrasubstituted C-N or C-C axially chiral olefins in excellent regioselectivity, enantioselectivity, and Z/E selectivity. Mechanistic studies reveal that the acyloxyamide participates unprecedentedly to generate an activated carbene instead of any nitrene intermediate, which circumvents the limited reaction patterns via nitrene and nitrogen radical in prior studies. The enantio- and the Z/E-determining steps of the catalytic cycle have been identified.