DBU-CATALYZED DECONJUGATION OF 7-SUBSTITUTED 3,4-DIDEHYDRO-2-OXEPANONES - DEUTERIUM INCORPORATION, SIGNIFICANCE OF THE IMINE DOUBLE-BOND, AND APPLICATION TO THE SYNTHESIS OF A KEY PHARMACOPHORE

7-Substituted 3,4-Didehydro-2-oxepanones are conveniently deconjugated to the 4,5-didehydro derivatives by DBU. The isomerization of 7-benzy l-substituted 2-oxepanones proceeds to the extent of 90% over the init ial 3 h; the concentration falls gradually thereafter to achieve, in 2 5 h, a 3:2 equilibrium in favor of deconjugation. Such an equilibrium does not exist for the 7-methyl and the 7-(2-phenethyl) derivatives. T he significance of the imine double bond in DBU has been explored. The isomerization in CDCl3 causes deuterium incorporation at positions 3 and 5 of the 2-oxepanones examined and at position 6 of DBU. The mecha nistic rationales for these deuterium incorporations are advanced. The transformation of 7-benzyl-3,4-didehydro-2-oxepanone into a bicyclo[3 .3.0] skeleton that is present in a diverse class of biologically acti ve natural products is described as a possible potential use of the pr esent deconjugation methodology.