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Mechanistic Insights into the Palladium-Catalyzed Aziridination of Aliphatic Amines by C-H Activation.


Type

Article

Change log

Authors

Smalley, Adam P 
Gaunt, Matthew J 

Abstract

Detailed kinetic studies and computational investigations have been performed to elucidate the mechanism of a palladium-catalyzed C-H activation aziridination. A theoretical rate law has been derived that matches with experimental observations and has led to an improvement in the reaction conditions. Acetic acid was found to be beneficial in controlling the formation of an off-cycle intermediate, allowing a decrease in catalyst loading and improved yields. Density functional theory (DFT) studies were performed to examine the selectivities observed in the reaction. Evidence for electronic-controlled regioselectivity for the cyclopalladation step was obtained by a distortion-interaction analysis, whereas the aziridination product was justified through dissociation of acetic acid from the palladium(IV) intermediate preceding the product-forming reductive elimination step. The understanding of this reaction mechanism under the synthesis conditions should provide valuable assistance in the comprehension and design of palladium-catalyzed reactions on similar systems.

Description

Keywords

Amines, Aziridines, Carbon, Catalysis, Hydrogen, Kinetics, Models, Molecular, Molecular Conformation, Palladium, Quantum Theory

Journal Title

J Am Chem Soc

Conference Name

Journal ISSN

0002-7863
1520-5126

Volume Title

137

Publisher

American Chemical Society (ACS)
Sponsorship
Engineering and Physical Sciences Research Council (EP/I00548X/1)
We are grateful to the EPSRC and Pfizer (A.P.S.) for a studentship and the ERC and EPSRC for fellowships (M.J.G.). We are also grateful to Dr Alex Thom and Dr David Pryde (Pfizer) for helpful discussions. The computational work was performed using the Darwin Supercomputer of the University of Cambridge High Performance Computing Service (http://www.hpc.cam.ac.uk/), provided by Dell Inc. using Strategic Research Infrastructure Funding from the Higher Education Funding Council for England and funding from the Science and Technology Facilities Council. Mass spectrometry data were acquired at the EPSRC UK National Mass Spectrometry Facility at Swansea University.