Aromatic motifs in the design of Ephedra ligands for application in the asymmetric addition of diethylzinc to aldehydes and diphenylphosphinoylimines

Using N-benzylephedrine as a model, a collection of N-arylmethylephedrine derivatives has been prepared. These derivatives were prepared by treatment of ephedrine with selected aldehydes to create oxazolidines 8a-e. Reduction of the oxazolidines with lithium aluminum hydride afforded the target β-amino alcohols 9a-e. When applied in the catalytic asymmetric addition of diethylzinc to aldehydes and diphenylphosphinoylimines, the derivatives yielded product enantioselectivities that were comparable to those of N-benzylephedrine. An N-cyclohexylmethylephedrine derivative was also prepared; this β-aminoalcohol did not perform well in the catalytic addition of diethylzinc to 2-naphthaldehyde, thus suggesting that the aromatic motif is important in terms of maintaining a reasonable level of asymmetric induction. Finally, N-benzyl-N-methyl-2-amino-1,2-diphenyl-1-ethanol, an analogue of the N-benzylephedrine derivative, was prepared. This compound yielded comparable enantioselectivities in the catalytic asymmetric addition when employed as a ligand.