Intramolecular Heck couplings of unactivated alkyl electrophiles : synthetic and mechanistic studies

Abstract

A method for the palladium-catalyzed intramolecular Heck coupling of unactivated alkyl bromides and chlorides is described. The optimal catalyst system was composed of Pd2(MeO-dba)3 as the metal source and N-heterocyclic carbene SIMes as the ligand, and the influence of both parameters is discussed. Reaction of a diastereomerically pure, deuterium-labeled substrate gave only one diastereomer of product, suggesting that the reaction does not proceed through radical pathway, in contrast to processes currently described in the literature. Mechanistic studies involved the synthesis of novel complex Pd(SIMes)2 and a number of its oxidative addition adducts, which were thought to resemble intermediates along a postulated catalytic cycle. However, the alkylpalladium species thus obtained, which were characterized by X-ray crystallography and which bear freely accessible 3 hydrogen atoms, are air and moisture-stable compounds that display no tendency for P-hydride elimination, even upon heating. These complexes are therefore not thought to be part of the catalytic cycle. It was further demonstrated that while Pd(SIMes)2 is not itself catalytically competent in the reaction, it may serve as a catalyst precursor. Evidence is provided to suggest that the true active catalyst is composed of a mixed ligand complex involving both SIMes and dba ...