Divergent Assembly of Fused Polycyclic Scaffolds from Iodotriazole-Tethered Benzaldehydes

Abstract

5-Iodo-1,2,3-triazoles tethered to a formyl group via an ortho-phenylene linker have been shown to be versatile precursors to a plethora of fused heterocyclic systems. A high reactivity of the aldehyde moiety toward nucleophilic addition enables in situ generation of various saturated azaheterocycles which induces further intramolecular iodine substitution in the triazole ring. The cascade assembly of structures combining triazole, quinazoline, and cyclic aminal units occurs readily under catalyst-free conditions upon heating in ethanol. The use of chiral β-aminoalcohols allows an easy construction of enantiopure polycyclic scaffolds in a diastereoselective fashion. A chemoselective oxidative cleavage of the hemiaminal ether fragment can be performed in a one-pot manner furnishing triazole-fused lactams.