Mechanistic investigation into the C(sp3)-H acetoxylation of morpholinones.

The study of a selective palladium(ii)-catalyzed C(sp3)-H acetoxylation reaction on a class of cyclic alkyl amines is reported. Computational modelling and kinetic studies were used to provide support for a mechanism involving selective C-O bond formation from a γ-aminoalkyl-Pd(iv) intermediate. The C-O bond forming step was computed to occur by a dissociative ionization mechanism followed by an SN2 process involving external acetate attack at the C-Pd(iv) bond. This pathway was computed to be of lowest energy with no competing C-N products observed. Additionally, with a few modifications to reaction conditions, preliminary studies showed that this process could be rendered enantioselective in the presence of a non-racemic BINOL-phosphoric acid.

Selective Reductive Elimination at Alkyl Palladium(IV) by Dissociative Ligand Ionization: Catalytic C(sp3 )-H Amination to Azetidines.

A palladium(II)-catalyzed γ-C-H amination of cyclic alkyl amines to deliver highly substituted azetidines is reported. The use of a benziodoxole tosylate oxidant in combination with AgOAc was found to be crucial for controlling a selective reductive elimination pathway to the azetidines. The process is tolerant of a range of functional groups, including structural features derived from chiral α-amino alcohols, and leads to the diastereoselective formation of enantiopure azetidines.

A general catalytic ß-C-H carbonylation of aliphatic amines to ß-lactams.

Methods for the synthesis and functionalization of amines are intrinsically important to a variety of chemical applications. We present a general carbon-hydrogen bond activation process that combines readily available aliphatic amines and the feedstock gas carbon monoxide to form synthetically versatile value-added amide products. The operationally straightforward palladium-catalyzed process exploits a distinct reaction pathway, wherein a sterically hindered carboxylate ligand orchestrates an amine attack on a palladium anhydride to transform aliphatic amines into ß-lactams. The reaction is successful with a wide range of secondary amines and can be used as a late-stage functionalization tactic to deliver advanced, highly functionalized amine products of utility for pharmaceutical research and other areas.