Studies on the synthesis of squaric acid ephedrine and their application in asymmetric catalytic borane reduction of prochiral ketones

Seven squaric acid ester amides or squaric acid diamides have been convenie ntly prepared by the reaction of natural ephedrine and squaric acid diester s, in which the later can be sythesized by refluxing squaric acid in the co rresponding alcohols. When squaric acid amide ester 4a reacted with alkyl a mines or was treated with aqueous sodium hydrosulfide, the new ligands whic h contain nitrogen or sulfur atom at C-3 of squaric acid were obtained. Fiv e ligands were synthesized for the first time. The chiral oxazaborolidines formed in situ have been used in the enantioselective borane reduction of p rochiral ketones and diketones to afford the alcohols in the range 85%-98% yields and 52.5%-87.4% enantiomeric excess respectively. All new ligand str uctures were comfirmed by IR, H-1 NMR, MS and elemental analysis, the cryst al structure of compound 4b was lerrified by X-ray diffraction.