Stereoselective Gram-Scale Synthesis of (S)-5,5-Dimethyl-4-phenyloxazolidin-2-one

A stereoselective gram-scale synthesis of (S)-5,5-dimethyl-4-phenyloxazolidin-2-one, SuperQuat [(S)-1], is described.The key step is the diastereoselective reduction of (E)-imine (2), which is synthesized from 2-hydroxy-2-methylpropiophenone ( 4) and (S)-α-methylbenzylamine using sodium borohydride and acetic acid to give (1S,αS)-2-methyl-1-(α-methylbenzyl)amino-1-phenylpropan-2-ol (5).SuperQuats [(S)-1 and (R)-1] (Figure 1) are excellent chiral auxialities developed by Davies et al. [1][2][3] for Evans-type asymmetric reactions and are widely applied to asymmetric α-alkylation, 1,4-6 conjugate addition, 1,3,4,7 cycloaddition, 8 epoxidation, 9 and kinetic resolution. 10After the asymmetric reactions of N-acyl SuperQuats the chiral auxialities are selectively cleaved to afford desired homochiral products. 5e selectivity of exocyclic cleavage is due to steric interactions between the geminal 5-C dimethyl groups and the nucleophile attacking at the carbonyl of the oxazolidin-2-one. 5Moreover, reductive cleavage of N-(α-substituted) acyl SuperQuats with DIBAH directly affords non-racemic α-substituted aldehydes without loss of stereochemical integrity. 4Figure 1.SuperQuats [(S)-1 and (R)-1] possessing a phenyl group and intermediates (2 and 3) for synthesis of (S)-1