Polymer-Assisted Asymmetric Reactions. 4. Polymer-Bound Ephedrine, Its Use and Limitations in Supported LiAlH₄ Reductions

A cross-linked polystyrene resin containing (1R,2S)-(-)-ephedrine moieties bound through nitrogen to some 1of its p-methylene-substituted aromatic rings is a useful regenerable chiral auxiliary in the enantioselective reduction of acetophenone by the chiral polymer-bound complexes of lithium aluminum hydride and an added achiral phenol. Evidence is presented to explain the capacity-dependent behavior of the polymer in the formation of chiral complexes and its effect on the enantioselectivity of the reduction of acetophenone. At high capacities, both unbound achiral and multiply bound chiral complexes are formed while numerous chiral ligands appear to be inaccessible to the hydride; under such conditions the enantioselectivity of the reaction is poor. In contrast, at low capacities corresponding to 8-10% substitution of the styrene repeating units, the polymer-bound chiral moieties can act independently from one another and are fully accessible to the hydride. The reduction then proceeds with a high enantioselectivity, comparable to that of similar small chiral molecules. This mechanism is consistent with and explains the phenomena observed with other polymer-supported hydride reagents.