An organometallic approach to the synthesis of heteropolycyclic compounds from benzenes

Abstract

Abstract The emerging field of dearomatization capitalizes on the synthetic potential of aromatic molecules. By using a transition metal to bind to two carbons of a benzene ring, the remaining four carbons are left available for the attachment of various chemical fragments. If these fragments are connected, this process could be a blueprint for synthesizing polycyclic architectures. The objective of this study is to develop a modular approach for creating classes of saturated polycyclic compounds that are currently underrepresented in the landscape of druggable chemical space. Herein, the phenyl group of methylphenylsulfone is coordinated to the tungsten complex {WTp(NO)(PMe3)}, largely interrupting its aromatic stabilization because of strong metal-to-ligand backbonding. Through the combination of ester enolate and amine addition reactions to the arene carbons, a wide array of chemically diverse polyheterocyclic systems is prepared. The tungsten stereogenic center influences the configurations of 3-5 stereocenters derived from the phenyl carbons.