New Directions in Palldium-Catalyzed Allylic Substitution

The palladium-catalyzed allylic substitution reaction is a powerful tool for the selective introduction of nucleophiles onto an allyl substrate. In simple acyclic substrates, control of the regio- and stereoselectivity is problematic. With regards to regiochemistry, allyl palladium complexes usually favor the addition of nucleophiles to the less hindered terminus of the allyl. Stereochemistry is often difficult to achieve because the allyl complex is not configurationally stable and undergoes allyl inversion. We have been exploring the palladium-catalyzed allylic substitution of chiral 5-vinyl oxazolidinones which afford intermediate metal complexes that are rapidly equilibrating diastereomers. Utilizing a reversible cyclization we can obtain oxazolines with thermodynamic control of stereochemistry.

With the addition of nitrogen nucleophiles like phthalimide, stereo- and regiochemistry is controlled through hydrogen bonding of the nucleophile to the adjacent amide. Thus we can obtain syn vicinal diamines with high selectivity.

We have found that chiral ligands influence the regioselectivity in the allylic amination with phthalimide. This led us to investigate a novel regiodivergent kinetic resolution, where 100% of a racemic substrate are converted to two different products with opposite configuration.