One-pot synthesis of 6-hydroxyisochromans: the example of demethyl-oxa-coclaurine

Using a modified oxa-Pictet Spengler reaction that we recently described, we synthesized 6-hydroxy-isochromans and their 7-hydroxy derivatives. The synthesis, which consists of one step and does not require protecting groups, was successful and provided high yields. The obtainment of 1-(4'-hydroxy-benzyl)-6,7-dihydroxy-isochroman (1) indicates that this protocol can be used to synthesize oxygenated analogues of benzyl-tetrahydroisoquinoline alkaloids, such as demethyl-coclaurine (2). This methodology could be applied as a general procedure for the synthesis of hydroxy-isochromans.