Experiments on the synthesis of tetracycline. Part VI. Oxidation and reduction of potential ring A precursors

Abstract

The reduction of substituted orcinol derivatives to dihydroaromatic compounds [specifically 2,6-dimethoxy-4-methylcyclohexa-2,5-dienecarboxamide (V)] is described. Attempted application of this reduction to the 3-dimethylamino-derivative (VI; R¹= NH₂, R²= Me, R³= NMe₂) was unsuccessful. As an alternative route, the addition of a nitrene to the double bond of an enol ether was studied.

The oxidation of a number of orcinol derivatives to the corresponding hydroxy-quinones is described. Attempts to hydrate these quinones were unsuccessful.

The formation of certain ortho-acyloxycyclohexadienones from phenols by use of lead tetra-acetate is described. For the preparation of the starting phenols, boron trichloride is a convenient demethylating agent. Our results indicate that this reagent, contrary to previous reports, may cause selective demethylation para to a carbonyl group in certain polyoxygenated benzenes.