Enantioselective Construction of Quaternary Stereocenters via A Chiral Spiro Phosphoric Acid-Assisted Formal Gold Carbene gem-Dialkylation Reaction.

Abstract

Enantioselective construction of all-carbon quaternary stereocenters has attracted much attention over the past few decades. A variety of catalytic asymmetric methods have been disclosed based on the use of presynthesized complex reagents that impart congested steric hindrance to the reaction center, which generally produce the chiral molecules through forming one C-C bond. The use of readily available reagents that could build two C-C bonds on the same carbonic center with the concomitant assembly of quaternary stereocenters remains challenging. Herein, we disclose a catalytic asymmetric alkyne multifunctionalization reaction using a gold complex and a chiral spiro phosphoric acid (SPA) for synergistic catalysis. In this method, the readily accessible internal alkynes served as the key gold carbene precursors, followed by carbene gem-dialkylation through Mannich-type addition of enolate species or stepwise formal cycloaddition with methylenimines that are derived from 1,3,5-triazinanes in the presence of SPA. The reaction provides practical access to poly-functionalized chiral linear and cyclic ketones that bear two adjacent quaternary stereocenters in generally good yields and excellent enantioselectivities, leading to an essential complement to the asymmetric construction of quaternary stereocenters using readily available materials with high bond formation efficiency.