Asymmetric Cross-Dehydrogenative Coupling of Glycinates via Iodine-Mediated Photoredox/Lewis Acid Synergistic Catalysis

The oxidative cross-dehydrogenative coupling (CDC) via
α-carbonyl
radicals significantly broadens the application scope of carbonyl
compounds as synthons, offering a promising approach for carbon–carbon
bond formation in organic synthesis. However, achieving cross-coupling
and stereocontrol under mild reaction conditions has remained a significant
challenge. Here, we report a synergistic catalytic platform that enables
highly diastereo- and enantioselective CDC of β-keto carbonyls
with glycine derivatives. The strategy introduces a photoredox catalyst
and a chiral magnesium complex catalyst, leveraging the oxidations
of the two coupling partners via independent pathways through the
use of peroxybenzoate and a catalytic amount of NaI under visible-light
irradiation. The β-carbonyl-substituted glycine derivatives
can be readily obtained with exceptional stereocontrol (up to >19:1
dr, >99% ee) and yield, spanning a series of glycinates with both
electron-donating and electron-withdrawing N-aryl
substitutions. Mechanistic studies reveal a radical pathway rather
than oxidative polar addition, showcasing a paradigm for merging photoredox-generated
open-shell intermediates in C(sp3)–H cross-coupling.