Synthesis of (+)-6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic Acid, a Diastereoselective Approach

The diastereoselective synthesis of (+)-6,7-dimethoxy1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid (90% ee) was accomplished by employing a combination of two synthetic methods, that is, the Petasis synthesis of amino acids and the Pomeranz-Fritsch-Bobbitt synthesis of tetrahydroisoquinoline derivatives. The stereochemical outcome of the synthesis was controlled by chiral aminoacetaldehyde acetals, which were used as the amine component of the Petasis step to yield the Pomeranz-Fritsch-Bobbitt substrate for the tetrahydroisoquinoline ring formation in one simple operation.