Rh(â…¢)-catalyed Synthetic Methodology Development Toward Heterocycles

Heterocycles are referred as privileged structures in drugs and natural products, which are important object of study in medical chemistry, organic synthesis and dye chemistry. Therefore, development of novel methodologies to access heterocycles has been one of the popular area in synthetic chemistry.In recent thirty years, researches on the transition-metal catalysis especially for C-H activation provide pharmaceutical chemists with powerful support to design and synthesize kinds of skeletons. In this thesis, Rh(III)-catalyzed synthetic methodology toward heterocycles was developed to access dihydroisoquinolinones, aromatic-fused azepinones, isoindolinones, indole-fused or pyrrole-fused heterocycles, (E)-stilbenes and functionalized cyclopentenes. Antiproliferative evaluation was carried out for some of these products.1. Rh(â…¢)-catalyzed C-H activation/cycloaddition of benzamides and MCPs for the selective synthesis of spiro dihydroisoquinolinones and furan-fused azepinones.2. Rh(â…¢)-catalyzed C-H activation/[4+3]cycloaddition of benzamides and vinylcarbenoids to access azepinones.3. Rh(â…¢)-catalyzed C-H activation/[4+1]cycloaddition of diazo compounds which are generated from ketones, hydrazines and MnO2 in one pot and benzamides to access isoindolinones.4. A simple derivation of indoles and pyrroles to the substrates containing oxidative directing group, which could take cyclization with alkynes, alkenes and diazo compounds, for access to indole-fused or pyrrole-fused heterocycles under Rh(â…¢)-catalysis.5. Rh(â…¢)-catalyed synthesis of 2-hydroxylated (E)-stilbenes was accomplished via oxidative coupling of 2-hydroxystyrenes and arylboronic acids. The antiproliferative evaluation of all the synthesized compounds was assessed on four different human cancer cell lines (Colo-205, MDA-468, HT29, and MGC80-3), and the preliminary results showed that several compounds exhibited strong antiproliferative activities (up to 35 nM).6. Rh(â…¢)-catalyzed C-H activation-desymmetrization of diazabicycles with arenes substituted by directing group to access functionalized cyclopentenes.