Lithium tert-butoxide-mediated efficient transesterification of N-hydroxyphthalimide esters toward oxime functionalization

Abstract

We report an efficient lithium tert-butoxide (LiO^tBu)-mediated transesterification of N-hydroxyphthalimide (NHPI) esters with oximes to afford oxime esters under mild conditions. This transition-metal-free method exhibits high chemoselectivity, broad substrate scope, and excellent yields (up to 99%) in acetonitrile (CH₃CN). Reaction optimization and scalability studies confirm its practical applicability. Mechanistic investigations and density functional theory (DFT) calculations reveal that LiO^tBu plays a pivotal role by generating a nucleophilic oximate intermediate, which subsequently reacts with NHPI esters through a lithium-assisted chelation pathway. The Lewis acidity of the Li⁺ ion is crucial for stabilizing the transition state and facilitating the transformation. This approach offers a simple and efficient strategy for the synthesis of a wide range of oxime ester derivatives, with significant potential for practical applications.