An efficient and convergent route for the synthesis of the natural product (+)-lithospermic acid, which possesses anti-HIV activity, was accomplished. The (±)-trans-dihydrobenzo[b]furan core therein was prepared by two different strategies. The first strategy involved the use of a palladium-catalyzed annulation to generate an appropriately substituted benzo[b]furan ester followed by a stereoselective reduction of a carbon–carbon double bond with Mg–HgCl2–MeOH. The second strategy relied on an aldol condensation between a suitably substituted methyl arylacetate and 3,4-dimethoxybenzaldehyde, followed by cyclization. Finally, a total synthesis of (+)-lithospermic acid was completed via coupling of a trans-dihydrobenzo[b]furan cinnamic acid with an enantiomerically pure methyl lactate.
