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

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

doi:10.1039/C8SC03434F

Mechanistic investigation into the C(sp³)–H acetoxylation of morpholinones†

Cornelia S. Buettner,‡^a Darren Willcox,

‡^a Ben. G. N. Chappell ‡^a and Matthew J. Gaunt

*^a

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* Corresponding authors

^a Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK
E-mail: mjg32@cam.ac.uk

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 S_N2 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.

This article is part of the themed collections: Sustainable synthesis and catalysis – Chemical Science symposium collection and 2019 Chemical Science HOT Article Collection

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Article information

DOI: https://doi.org/10.1039/C8SC03434F
Article type: Edge Article
Submitted: 02 Aug 2018
Accepted: 28 Sep 2018
First published: 01 Oct 2018
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry

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Chem. Sci., 2019,10, 83-89

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

C. S. Buettner, D. Willcox, Ben. G. N. Chappell and M. J. Gaunt, Chem. Sci., 2019, 10, 83 DOI: 10.1039/C8SC03434F

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