Synthesis of (±)-aporphine utilizing Pictet–Spengler and intramolecular phenol ortho-arylation reactions

A synthesis of the alkaloid (±)-aporphine is reported. The initial key step of the synthesis involves a Pictet–Spengler cyclization of N-tosyl tyramine with 2-bromophenylacetaldehyde in trifluoroacetic acid. This step was followed by the second strategic transformation a palladium-mediated intramolecular phenol ortho-arylation reaction utilizing tricyclohexylphosphine as co-catalysts in the presence of cesium carbonate. Finally, de-oxygenation of the phenol, removal of the tosyl group and methylation gave the desired alkaloid.