Multicomponent Assembly and Diversification of Novel Heterocyclic Scaffolds Derived from 2-Arylpiperidines

A collection of structurally diverse, polyheterocyclic scaffolds comprising a 2-arylpiperidine subunit were synthesized using a Mannich-type multicomponent assembly process, followed by appropriately sequenced ring-forming reactions. An improved procedure for removal of N-4-pentenoyl groups was developed; one-pot sequences for tandem urea/thiourea formation and cyclization and tandem enolate arylation/alkylation were discovered. A novel entry to bridged tetrahydroquinoline scaffolds exploiting A1,3 strain was also invented. Derivatization of several scaffolds was achieved by cross-coupling and N-functionalization.