Ruppert-Prakash Reagent (TMSCF3)-Catalyzed Chemoselective Esterification of Weinreb Amides

A straightforward TMSCF3-catalyzed conversion of Weinreb amides into esters through the treatment with sodium alkoxides is reported. The procedure documents a genuine selectivity for the esterification of primary alcohols with Weinreb amides featuring diverse substitution pattern. The constitutive N-methoxy fragment of these acylating agents is responsible for the unique reactivity they display, thus enabling to explore alkoxides as competent nucleophilic elements. The protocol is compatible with the fully transfer of stereochemical information embodied in the starting material, as well as, guarantees the preparation of pharmaceuticals. Mechanistic investigations revealed that under the adopted reaction conditions (NaOR, R primary) TMSCF3 does not release the trifluoromethyl (CF3-) anion – as occurs with tertiary alkoxides - but rather it catalytically activates the amidic bond.