A Short Synthetic Route to (+)-Austamide, (+)-Deoxyisoaustamide, and (+)-Hydratoaustamide from a Common Precursor by a Novel Palladium-Mediated Indole → Dihydroindoloazocine Cyclization

The first synthesis of (+)-austamide (1), (+)-deoxyisoaustamide (2), and (+)-hydratoaustamide (10) by a very direct route is described (Scheme ). Starting from tryptophan methyl ester (3) intermediate 5 is generated in two steps in >98% overall yield. The key step in the synthesis is a novel cyclization of 5 involving organopalladium intermediates which gives the dihydroazocine 6. From this key intermediate the target structures are accessible in just a few steps as shown in Scheme . The remarkable conversion of 5 → 6 can be rationalized by the mechanistic pathway shown in Scheme that involves a multistep sequence which includes palladation, cyclization, and rearrangement.