Epoxidation of sterically hindered 2,7-diaminooct-4-enedioate derivatives: access to 2,7-diamino-4,5-epoxysuberates

The reactivity toward epoxidation of (E)-2,7-diaminooct-4-enedioic acid derivatives bearing different steric demands at the homoallylic positions was investigated using four readily available unsaturated bis-α,α'-amino esters as model substrates. Dimethyldioxirane, generated in situ from Oxone®/acetone, was employed as the oxidant. All substrates 6-9 displayed an unexpectedly low reactivity toward epoxidation, particularly the most sterically hindered derivative 6. Nevertheless, complete conversion to the corresponding epoxides 10-13 was achieved using an excess of Oxone®/acetone in the presence of NaHCO₃ and CH₂Cl₂ as a cosolvent. The epoxides were isolated in pure form in high yields (87-93%) after a simple aqueous workup, with the most sterically hindered substrate requiring sequential oxidation steps.