Enantioselective Synthesis of α-Oxygenated Ketones via Organocatalytic Formal O–H Bond Insertion of Sulfonium Ylides

Described here is an example of organocatalytic enantioselective formal O-H bond insertion of α-carbonyl sulfur ylides, providing efficient access to highly enantioenriched ketones bearing a tertiary α-oxygenated stereocenter. This metal-free approach is complementary to the well-established metal-based diazo carbonyl chemistry, which has gained broad success for esters but not for ketones. The proper choice of a chiral thiourea catalyst in combination with <i>N</i>-hydroxyl phthalimides proved to be crucial to success. Mechanistic studies indicate that the reaction is likely initiated by activation of sulfonium ylides by hydrogen bonding, thus distinct from previous related cases using chiral phosphoric acid catalysis that involves initial protonation of the basic sulfonium ylide functionality. DFT studies provided important insights into the key C-O bond-forming intermediates and transition states.