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Updated: Mar 25, 2026

A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis
Published on: February 16, 2020
Palladium-Catalyzed Directed C(sp3)-H Arylation of Saturated Heterocycles at C-3 Using a Concise Optimization
Dominic P Affron1, James A Bull1
1Department of Chemistry, Imperial College London, South Kensington, London SW7 2AZ, United Kingdom, http://www3.imperial.ac.uk/people/j.bull.
Abstract:
Saturated heterocycles, such as THFs, pyrrolidines, piperidines and THPs, are essential components of many biologically active compounds. Examples of C-H functionalization on these important ring systems remain scarce, especially at unactivated positions. Here we report the development of conditions for the palladium-catalyzed stereoselective C(sp3)-H arylation at unactivated 3-positions of 5- and 6-membered N- and O-heterocycles with aminoquinoline directing groups. Subtle differences in substrate structures altered their reactivity significantly; and different conditions were required to achieve high yields in each case. Successful conditions were developed using a short empirical optimization approach to cover reaction space with a limited set of variables. Excellent cis-selectivity was achieved in all cases, except for the THP substrate where minor trans-products were formed through a different palladacyclic intermediate. Here, differences in reactivity and selectivity with other directing groups were examined.
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