A Novel Sc(OTf)3-Catalyzed (2+2+1)-Cycloannulation/Aza-Friedel-Crafts Alkylation Sequence toward Multicyclic 2-Pyrrolines

The rapid assembly of molecular complexity continues to be at the forefront of novel reaction development. In the pursuit of that goal, we herein report a novel Sc(OTf)(3)-catalyzed, one-pot multicomponent reaction that furnishes complex multicyclic 2-pyrrolines with excellent overall yields and perfect diastereocontrol. This process is based on our previously established (2+2+1)-cycloannulation of in situ generated 1-azaallyl cations, 1,3-dicarbonyls and primary amines. The newly formed and highly reactive aminal moiety is readily substituted with indoles and pyrroles both as external and internal -nucleophiles to provide densely functionalized N-heterocycles with four new sigma-bonds and two vicinal quaternary stereogenic centers. In addition, DFT calculations have been conducted to further characterize the intermediate 1-azaallyl cations.