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

Cornelia S Buettner,Ben G N Chappell,Darren Willcox,Matthew J Gaunt

doi:10.1039/c8sc03434f

Cornelia S Buettner, Ben G N Chappell + Show 2 more

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https://doi.org/10.1039/c8sc03434f

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Abstract

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.

Highlights

The study of a selective palladium(II)-catalyzed C(sp3)–H acetoxylation reaction on a class of cyclic alkyl amines is reported
By Sanford and co-workers, on C–H acetoxylation has led to three distinct mechanistic rationales being proposed for the reductive elimination pathway: (1) direct reductive elimination from palladium(IV) without loss of a ligand; (2) dissociative neutral (DN) where a L-type ligand dissociates to form a neutral vecoordinate palladium(IV) intermediate followed by reductive elimination and (3) dissociative ionization (DI), where a X-type ligand dissociates forming a ve-coordinate cationic palladium(IV) species prior to reductive elimination (Scheme 1a).[3]
Further investigations and DFT modelling studies into C(sp3)–H acetoxylation reactions, using model palladium(IV) intermediates, indicated that a dissociative ionization mechanism is the major pathway for carbon–oxygen reductive elimination (Scheme 1b).[4]

Summary

Introduction

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 g-aminoalkyl-Pd(IV) intermediate.

Results

Conclusion