Diastereoselective Alkylation of 4-Methyl-5-oxo-2-phenyl-1,3-oxazolidine-3-carboxylate and 2-Chloromethyl-isoindole-1,3-dione

Abstract

Asymmetric synthesis, that is, 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 for an oxazolidin-2-one chiral auxiliary derived from a NNAA followed by quenching this enolate with 2-chloromethyl-isoindole-1,3-dione to provide an α-methyl NNAA building block equipped with a phthalimide group in good yield through a multistep synthesis with no signs of any minor diastereomers. The identity of this compound was confirmed by ¹H NMR (Proton Nuclear Magnetic Resonance) and ¹³C NMR (Carbon-13 Nuclear Magnetic Resonance) spectroscopy. With the availability of this building block, peptides can be produced and evaluated over a variety of therapeutic areas in drug discovery.