Diastereoselective Alkylation of an Oxazolidinone Chiral Auxiliary

Abstract

Asymmetric synthesis, the part of diastereoselective alkylation of a chiral auxiliary is an important tool in organic synthesis. In this work an α-methyl, non-natural amino acid (NNAA) building block equipped with a phthalimide group tail was prepared. This work describes the generation of the lithium enolate oxazolidin-2-ones chiral auxiliary derived from non-natural amino acid and quenching this enolate with 2-chloromethyl-isoindole-1,3-dione, to provide an α-methyl, non-natural amino acid (NNAA) building block equipped with a phthalimide group in good yield in multistep synthesis with no sign of any minor diastereomers. The identity of new compound was confirmed by ¹H, ¹³C NMR and mass spectrometry. With this building block in hand, peptides can be produced for evaluation in a variety of therapeutic areas in drug discovery.