Modular Furanoside Phosphite‐Phosphoroamidites,a Readily Available Ligand Library for Asymmetric Palladium‐Catalyzed Allylic Substitution Reactions. Origin of Enantioselectivity

A library of furanoside phosphite‐phosphoroamidite ligands has been synthesized and screened in the palladium‐catalyzed allylic substitution reactions of several substrate types. These series of ligands can be prepared efficiently from easily accessible D ‐xylose and D ‐glucose. Their modular nature enables the position of the phosphoroamidite group, configuration of C‐3 of the furanoside backbone and the substituents/configurations in the biaryl phosphite/phosphoroamidite moieties to be easily and systematically varied. By carefully selecting the ligand components, therefore, high regio‐ and enantioselectivities (ees up to 98%) and good activities have been achieved in a broad range of mono‐ and disubstituted hindered and unhindered linear and cyclic substrates. The NMR studies on the palladium‐π‐allyl intermediates provide a deeper understanding about the effect of the ligand parameters on the origin of enantioselectivity. They also indicate that the nucleophilic attack takes place predominantly at the allylic terminal carbon atom located trans to the phosphoroamidite moiety.