Enantioselective Oxidative Cyclization/Mannich Addition Enabled by Gold(I)/Chiral Phosphoric Acid Cooperative Catalysis

An enantioselective Mannich‐type reaction of 3‐butynol and nitrones is described, which affords dihydrofuran‐3‐ones in good yields and with excellent enantioselectivities. The reaction is initiated by gold‐catalyzed alkyne oxidation and modification of the resulting gold carbene species with a tethered hydroxy group to form enolate species; the reaction terminates with an enantioselective Mannich‐type addition with the assistance of chiral phosphoric acid (CPA) and hydrogen bonding. This novel pattern of alkyne transformation involving chemical bond cleavage, and a fragment modification and reassembly process, provides an atom‐ and step‐economic method, and is the first example of cooperative asymmetric catalysis in gold‐catalyzed alkyne oxidations via an α‐oxo gold carbene route. Golden oldie: A combination of gold(I) and chiral phosphoric acid (CPA) catalyzes a Mannich‐type reaction cooperatively. Asymmetric trapping of a gold enolate intermediate involved in alkyne oxidations occurs via an α‐oxo gold carbene route. Alkyne transformation involves 1) chemical N−O bond cleavage, 2) fragment modification, and 3) reassembly.