Regioselective Reductive Electrophilic Substitution of Derivatives of 3,4,5-Trimethoxybenzaldehyde

The behavior of several protected derivatives of 3,4,5-trimethoxybenzaldehydeh as been investigated under conditions of electron transfer from alkali metals in aprotic solvents. The 4methosy group can be regioselectively removed in good to high yield under such conditions, and an appropriate choice of the protecting group, metal, and solvent allows its substitution with a variety of electrophiles. 3,4,5-"rimethoxybeddehyde dimethyl acetal, 1, is the starting material of choice for a new general synthetic approach to several polysubstituted resorcinol dimethyl ethers. Inveatigation of the m e d " of demethoxylation, with the aid of labeling experiments, showed that reductive demethoxylation is strongly influenced by the nature of the aldehyde protective group employed.