Divergent reaction pathways in amine additions to β-lactone electrophiles. An application to β-peptide synthesis

β-Lactone electrophiles are subject to regioselective addition–elimination (AE) or SN2 ring opening with various nitrogen-based nucleophiles. Primary and secondary amines promote AE ring opening to deliver products that are the functional equivalent of amide aldol adducts. Azide and sulfonamide anion nucleophiles engender SN2 lactone ring opening to deliver N-protected β-amino acid derivatives. These nucleophile-dependent ring opening pathways, coupled with the convenient access to highly enantoenriched β-lactones afforded by acyl halide–aldehyde cyclocondensations, constitute versatile methodologies for asymmetric organic synthesis. The application of this reaction technology to a new method for β-peptide synthesis based on the optically active β-azido acids emerging from the AAC-ring opening sequence is also described.