Enantioselective formation of oxazolidinones from 2-substituted serinols

Abstract

The chiral quarternary carbon with nitrogen atom is considered as valuable building blocks, which are found in various physiologically potent natural products, such as sphingofungin, lactacystin, salinosporamide A, kaitocephaline, lepardiformine etc. To the best of our knowledge, the methodologies of the enantioselective formation of t-alkylamines have been inefficient and rare. Recently, our group reported enantioselecive monobenzoylation of 2-substituted 2-benzamido-1,3-propanediols by catalytic desymmetrization to install quaternary carbon centers. Although this enantioselective monobenzoylation method was highly efficient in chemical yield and enantioselectivity, it had problems of practical use in organic synthesis. Herein, we report highly effective enantioselective formation of oxazolidinones from 2-substitued serinols via asymmetric tandem catalysis. The effective desymmetrization has been implemented using phenyl carbamate protected substrates with N,N-dimethyl benzylamine 127 in the presence of 5 mol% of the dimethyl phenyl bisoxazolidine (94)-CuCl2 complex in toluene at room temperature. Furthermore, subsequent asymmetric benzoylations via kinetic resolution in a pot enhance the enantioselectivity of the substrates in toluene and THF mixture. As a result, we reduced the amount of the chiral ligand copper complex from 20 mo% to 5 mol% in terms of the methodology. And we could get desired substrates with good chemical yields (70~89%) and excellent enantioselectivities (93~99% ee). In terms of practical organic synthesis, prepared benzoyl protected oxazolidinones are advantageous in further protections of the substrates to make unreactive for the other chemical reactions and deprotections to transform different functional groups.