Sequential Combination of Ruthenium‐, Base‐, and Gold‐Catalysis – A New Approach to the Synthesis of Medicinally Important Heterocycles

A general approach to the high‐yielding synthesis of medicinally important heterocycles was achieved through the sequential combination of ring‐closing metathesis, base‐induced ring opening (BIRO), hydroamination, and a Diels–Alder reaction of functionalized allyl‐(2‐allylphenyl)amines in the presence of a catalytic amount of Grubbs' second‐generation catalyst, base ( t BuOK), and [AuCl(PPh 3 )]/AgOTf. Herein, we also demonstrate the important electronic factors in the BIRO of N‐substituted‐benzo[ b ]azepines for the regioselective synthesis of functionalized ( Z )‐N‐substituted‐2‐(buta‐1,3‐dienyl)phenylamines in very good yields with high purity; these are very good, useful compounds in medicinal chemistry. We also discovered the selective cascade synthesis of privileged hexahydrophenanthridines from ( Z )‐N‐substituted‐2‐(buta‐1,3‐dienyl)phenylamines by gold catalysis in moderate to good yields with >99 % diastereomeric excess. The possible reaction mechanism for the unusual hydroamination followed by [4+2] cycloaddition of functionalized ( Z )‐ N ‐substituted‐2‐(buta‐1,3‐dienyl)phenylamines through gold catalysis is discussed in this work.