Regioselective metal-free synthesis of sulfostyril-quinoline hybrid framework: Experimental and computational mechanistic insights

Abstract

Polycyclic sultams are widely encountered in both natural products and bioactive drug candidates. In cognizance to their synthetic and medicinal chemistry applications, the exploration of facile approaches remains at high demand. In the present work, a straightforward, efficient and operationally simple methodology has been developed. The coupling of β-chloroaldehyde with a diverse range of anilines as bis-nucleophile containing NCC fragment was achieved to deliver a sulfostyril-quinoline hybrid framework. The formation of target scaffolds bearing various substituents avoiding the need of column chromatographic purification represents one of the key advantages associated with this transformation. The exclusive regioselectivity achieved for the formation of linear tetracyclic products over angular products was corroborated with density functional theory (DFT) calculations as well as single crystal X-ray analysis. Furthermore, the density functional theory calculations allowed us to understand the formation of tetracyclic sulfostyril-quinoline hybrid skeleton, and are in fair agreement with the observed regioselectivity of this reaction.