A New Synthesis of Chiral Oxazolidinones from the Amino Acid L-serine

Cyclization of the (4S)-PhCH2OCONHCH(CH2OH)CONHN=CH-aryl, obtained in 4 steps from L-serine, on treatment with MeI and potassium carbonate, generates the chiral oxazolidinones, (4S)-N'-[(E)-(phenyl)methylidene]-Nmethyl- 2-oxo-1,3-oxazolidine-4-carbohydrazides. Overall the formation of the (4S)-N'-[(E)-(phenyl)methylidene]-Nmethyl- 2-oxo-1,3-oxazolidine-4-carbohydrazides from L-serine occurs with retention of configuration, as confirmed by Xray crystallography. In contrast, the reaction of the N-Boc analogues, (4S)-t-BuOCONHCH(CH2OH)CONHN=CH-aryl, on treatment with MeI / K2CO3, simply leads to N-methylation without cyclization and without loss of the Boc protecting group to give (4S)-t-BuOCONMeCH(CH2OH)CONHN=CH-aryl. The difference between the Boc and Cbz derivatives is striking and is probably linked to the greater bulk of the Boc group blocking the intramolecular acyl transfer.