The asymmetric synthesis of β-lactams: HETPHOX/Cu(I) mediated synthesis via the Kinugasa reaction

The reactions of nitrones with terminal alkynes, catalysed by a range of HETPHOX ligands afforded β-lactams in moderate to good conversions with ees up to 55%. High levels of diastereoselectivity, dependent on the alkyne, were obtained. For example, the reaction is highly cis-diastereoselective with phenylacetylene (>9:1), while an unexpected reversal of diastereoselectivity is observed with the 3,5-trifluoromethyl phenylacetylene, which is highly trans selective (1:9) with an ee of 53%. The reaction scope with differently substituted nitrones and phenylacetylenes was also studied.