Facile access to chiral ketones through metal-free oxidative C-C bond cleavage of aldehydes by O2.

Functionalized chiral ketones, such as a-amino ketones, bnitro ketones, and their derivatives, are prevalent building blocks and ubiquitous subunits present in natural products and pharmaceutical lead compunds. The synthesis of chiral ketones can be achieved through direct a substitution. For example, the synthesis of a-amino ketones has been developed by Jørgensen and co-workers using an elegant catalytic amination of ketones by diethyl diazenedicarboxylate (DEAD). Despite the success, some drawbacks of this method lie in the unsatisfactory and undesired regioselectivities for unsymmetric ketones, and to a certain extent the demanding reaction conditions required for subsequent N N bond cleavage. Another approach for chiral ketone synthesis employs N-heterocyclic carbene catalysis. Rovis and coworkers have recently reported excellent asymmetric Stetter reactions of aldehydes to nitroalkenes to afford b-nitro ketones. The aldehyde substrates are restricted to (hetero)aryl aldehydes and enals as the acyl anion precursors, and usually only aliphatic nitroalkenes can behave as effective Michael acceptors. We envisioned that limitations associated with current new bond-forming reactions for chiral ketone synthesis could be substantially overcome by a less common C C bond-breaking approach (Scheme 1).