Synthesis of alpha-Oxygenated Carbonyl Compounds via Dioxygenation, Development of Flourescent Probes

An alternative route to α-oxygenated carbonyl compounds through the dioxygenation of vinyl boronic acids has been developed. This new transformation avoids the use of unstable reagents and provides an efficient direct route from internal alkynes to α-oxygenated ketones. This procedure involves the copper-catalyzed etherification of N-hydroxy phthalimide with boronic acids and a subsequent [3,3] rearrangement, followed by hydrolysis under acidic conditions to form either the corresponding α-hydroxy ketones or the α-benzoyloxy ketones. Our initial discovery was then modified to provide the diastereoselective dioxygenation of vinyl boronic acids with 3-hydroxyisoindolinones. This transformation is dependent on the identity of the hydroxyisoindoline protecting group and gives single diastereomer rearrangement products from chiral non-racemic hydroxyisoindolines. This new method provides access to enantioenriched α-hydroxyketones, which are important chiral building blocks for the synthesis of a number of natural products. New libraries of environmentally sensitive and thiol-reactive fluorescent probes with tunable emission properties and high photostability for in situ quantitative imaging of cellular lipids were designed and synthesized. These new probes have been used for the spatiotemporal quantification of phosphatidylserine in the E.coli cell.