Issue 5, 2022

C(sp3)–H oxygenation via alkoxypalladium(ii) species: an update for the mechanism

Abstract

Pd-catalyzed C(sp3)–H oxygenation has emerged as an attractive strategy for organic synthesis. The most commonly proposed mechanism involves C(sp3)–H activation followed by oxidative addition of an oxygen electrophile to give an alkylpalladium(IV) species and further C(sp3)–O reductive elimination. In the present study of γ-C(sp3)–H acyloxylation of amine derivatives, we show a different mechanism when tert-butyl hydroperoxide (TBHP) is used as an oxidant—namely, a bimetallic oxidative addition-oxo-insertion process. This catalytic model results in an alkoxypalladium(II) intermediate from which acyloxylation and alkoxylation products are formed. Experimental and computational studies, including isolation of the putative post-oxo-insertion alkoxypalladium(II) intermediates, support this mechanistic model. Density functional theory reveals that the classical alkylpalladium(IV) oxidative addition pathway is higher in energy than the bimetallic oxo-insertion pathway. Further kinetic studies revealed second-order dependence on [Pd] and first-order on [TBHP], which is consistent with DFT analysis. This procedure is compatible with a wide range of acids and alcohols for γ-C(sp3)–H oxygenation. Preliminary functional group transformations of the products underscore the great potential of this protocol for structural manipulation.

Graphical abstract: C(sp3)–H oxygenation via alkoxypalladium(ii) species: an update for the mechanism

Supplementary files

Article information

Article type
Edge Article
Submitted
10 Dec 2021
Accepted
13 Jan 2022
First published
13 Jan 2022
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2022,13, 1298-1306

C(sp3)–H oxygenation via alkoxypalladium(II) species: an update for the mechanism

S. Zhang, J. Zhang and H. Zou, Chem. Sci., 2022, 13, 1298 DOI: 10.1039/D1SC06907A

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements