Rapid access to divergent fused polycycles via one‐pot A3 coupling and intramolecular Diels‐Alder reaction

Divergent nitrogen‐containing fused polycyclic ring systems are constructed from simple starting materials via a one‐pot aldehyde‐alkyne‐amine (A³) coupling and intramolecular Diels‐Alder reaction. This domino reaction directly furnishes linear 5/5/5 and 5/5/6, or nonlinear 5/5/6/5, polycyclic rings containing an oxa‐bridged fused 5/5 bicycle and a 1,6‐enyne substructure. One‐step derivation of the oxa‐bridged 5/5 bicycle leads to a polyfunctionalized 5/5 bicycle with tetrahydrofuran fused back‐to‐back to pyrroline or a 6/5 bicycle with the hexahydro‐1H‐isoindole structure, while cycloisomerizing the enyne substructure adds an extra fused 5‐membered ring to afford functionalized linear 5/5/5/5 or 5/5/5/5/5 fused ring systems from selected substrates. In addition, the one‐pot product can be designed so that the alkyne moiety is hydroalkoxylated to form an additional heterocyle in a linear 5/5/5/6 or nonlinear 5/5/6/5/5 ring system. This diversity‐oriented synthetic approach thus allows rapid access to an under‐explored structural space for discovery of new biological or non‐biological activities or functions.