Synthesis of Fused 3‑Aminoazepinones via Trapping of a New Class of Cyclic Seven-Membered Allenamides with Furan

Novel
tricyclic tetrahydroazepinones were synthesized via an in
situ Diels–Alder reaction of furan with cyclic
allenamides. These reactive intermediates are the first examples of
cyclic seven-membered allenamides and were prepared starting from N-(2-chloroallyl)-2-allylglycine derivatives via ring-closing
metathesis followed by dehydrochlorination. The trapping of the intermediate
cycloallene with furan occurred endo- and regioselectively
and provided a convenient entry into new building blocks for medicinal
chemistry. The diastereoselectivity of the cycloaddition was confirmed
using quantum chemical computations.