An Efficient Synthesis of Acetylated Bicyclic Hydroxypyrroles from Cyclic Lactams via Flash-Vacuum Pyrolysis of Meldrum's Acid Derivatives

Article abstract of DOI:10.1021/jo00259a013

The title compounds 9 were synthesized in three steps from cyclic lactams 2.After treatment of 2a-h with phosgene followed by the addition of Meldrum's acid to the chloroiminium chloride intermediates 3a-h, derivatives 4a-h were isolated in good yields.Compounds 4a-g were quantitatively converted to bicyclic enaminones 7a-g by flash-vacuum pyrolysis in the temperature range 480-600 deg C.In contrast, 4h provided 8h, the hydroxyprrole tautomer of 7h.The reaction takes place through the initial formation of (aminomethylene)ketenes 5a-h followed by a 1,4-hydrogen migration from the carbon adjacent to the nitrogen atom to the central carbon of the cumulenone.The lower temperature (480 deg C) needed for benzyl and N-carboalkoxy derivatives 4e-h in comparison with N-alkyl derivatives 4a-d (600 deg C) is correlated with gas-phase acidity of the migrating hydrogen atom.The hydroxypyrroles 8a-g, tautomers of 7a-g (7<-->8), were trapped with acetic anhydride, affording O-acetylated bicyclic hydroxypyrroles 9a-g.