Stereochemistry of the Reactions between Palladacycle Complexes and Primary Alkyl Iodides

Abstract

As an important elementary step in organometallic chemistry, the alkylation reaction of palladacycle complexes and alkyl halides has attracted much attention in recent years due to their presence as a key step in palladium-catalyzed C–H alkylation reactions. In principle, several alkylation mechanisms, such as the stereoinvertive SN2-type mechanism and the stereoretentive oxidative addition mechanism, can be operative, and mechanistic insights can be obtained from the stereochemical outcomes of these alkylation reactions. Previous stereochemical investigations on the alkylation reaction of palladacycle complexes mainly focused on the use of chiral secondary alkyl halides as stereochemical probes, leaving more synthetically relevant primary alkyl iodides untouched. In this work, deuterium-labeled primary alkyl iodides were selected as a stereochemical probe, and their reaction with C,C- and C,N-type palladacycle complexes, namely, Catellani-type palladacycle intermediates and directing group (DG)-coordinated palladacycle complexes, were investigated both experimentally and computationally to elucidate the alkylation mechanism. We found that the C,C-ligated palladacycle intermediates undergo alkylation through the SN2-type mechanism, while the C,N-ligated 8-aminoquinoline-derived palladacycle complex favors a stereoretentive oxidative addition mechanism. In addition, the 2-phenylpyridine-derived C,N-type palladacycle dimer complex was found to react through the SN2-type mechanism due to its stable dimer structure and the d8–d8 interaction between two palladium atoms.