Desymmetrization of Malonic Monoesters and Malonic Acids via Enantioselective Catalytic C(sp ³ )─H Oxidation

ABSTRACT Malonate derivatives are readily available starting materials widely employed in the synthesis of bioactive compounds. Herein, we report a novel catalytic protocol for the direct desymmetrization of malonic acids via enantioselective C(sp 3 )─H bond functionalization. Highly enantioselective (up to >99% ee) γ ‐ and δ ‐ C─H bond lactonization of readily available malonic acid monoesters and malonic acids is achieved, using manganese catalysts and hydrogen peroxide as the oxidant. Owing to the ease and versatility of malonic acid derivative synthesis, combined with the potential post‐oxidation elaboration, this methodology overcomes the inherent lack of reactivity of the electron‐poor C(sp 3 )─H bonds of this class of substrates against electrophilic oxidants to provide straightforward access to a broad range of quaternary stereocenters that can be orthogonally manipulated.