A concise synthesis of naphthalene compounds for incorporation into a synthetic sequence for therubromycin family of natural products is presented. These highly substituted naphthalenes are generatedin seven and nine steps, respectively, from 2,4,5-trimethoxybenzaldehyde. Three ring-forming methodswere explored and the controlled oxygenation of different positions was investigated to yield differentiallysubstituted/protected systems. Key steps to the final products include a Stobbe condensation to form thering system and a novel series of regioselective oxidations to introduce the required oxygen functionality.These naphthalene products incorporate orthogonal protecting groups and are suitable for combinationwith a variety of coupling partners.
