Diastereoselective Reductive Amination of β-Hydroxyketones

Significance

This article proposes an expedient way for preparing chiral 1,3-syn-amino alcohols from various enantiopure β-hydroxyketones by a Lewis acid promoted reductive amination. Hereby, Ti(Oi-Pr)₄ assumes the role of the activating and directing metal species and polymethylhydrosiloxane (PHMS) serves as hydride donor. The ketones are converted with p-anisidine into the respective imine intermediates. Various chiral 1,3-syn-amino alcohols are thus obtained in good diaste­reo­meric ratios ranging from 86:14 to 93:7. In order to underline the importance of this reaction in drug development, it was additionally applied to the preparation of a key intermediate in the syntheses of ritonavir and lopinavir, which are both known HIV-protease inhibitors.