Chiral Mixed Phosphorus/Sulfur Ligands for Palladium-Catalyzed Allylic Alkylations and Aminations.

Abstract

The incorporation of C2 symmetry into chiral ligand design is a well-recognized strategy for restricting the number of diastereomeric transition states in metal-catalyzed enantioselective processes.1 Equally powerful stereochemical restrictions may also be realized with chiral ligands lacking C2 symmetry through the use of electronic effects such as the trans influence.2 Such effects are a natural consequence of the use of chiral bidentate ligands equipped with strong and weak donor heteroatom pairs (e.g., PR3/NR3 or PR3/SR2). Such electronic effects have the potential to influence both the stability and reactivity of the intervening diastereomeric reaction intermediates in the catalytic cycle. While mixed phosphorus/nitrogen bidentate ligands incorporating this construct have been applied in enantioselective palladiumcatalyzed nucleophilic alkylation of allylic esters,3 chiral thioether-containing donor ligands have been less well developed.4 As seen in structure A, thioether complexation creates an S-chiral sulfur center; however, a potential liability associated with these ligands is the relatively low barrier to sulfur inversion (15-20 kcal/mol) for transition metal-coordinated thioethers.5 In this paper, we report a new class of mixed phosphorus/sulfur ligands 1-3 that incorporates a metal-bound thioether as a chiral control element in asymmetric catalysis. The utility of these ligands is illustrated in the palladium-catalyzed allylic alkylation6 with enol-malonate and amine nucleophiles.