We are engaged in the first systematic efforts to exploit catalytic ketone/unsaturated moiety coupling via C-C activation. Our objective, in the proposed funding period, is to develop a "Cut and Sew" strategy for the efficient synthesis of bridged/fused ring systems via catalytic C-C activation, which includes 1) regular "Cut and Sew": Rh- or Co-catalyzed intramolecular carboacylation with both strained and unstrained cyclic ketones;2) decarbonylative "Cut and Sew": catalytic intramolecular couplings between cyclic ketones and unsaturated moieties with CO extrusion. The research proposed is expected to provide a general and unified strategy to build complex skeletons, found in numerous natural products and drugs, from simple starting materials.
Complex ring structures exist in over 60% of natural products and pharmaceutical compounds, and these scaffolds generally play key roles in their biological activity. However, chemical synthesis of these ring systems proves challenging, and current approaches need to be improved. Employing our recently developed C-C activation strategy, the outlined proposal provides rapid/general access to the core skeletons of various biologically important molecules in a catalytic and byproduct-free manner, which, in turn, would significantly expedite the synthesis of these molecules and ultimately accelerate drug discovery.
|Xu, Tao; Savage, Nikolas A; Dong, Guangbin (2014) Rhodium(I)-catalyzed decarbonylative spirocyclization through C-C bond cleavage of benzocyclobutenones: an efficient approach to functionalized spirocycles. Angew Chem Int Ed Engl 53:1891-5|
|Xu, Tao; Dermenci, Alpay; Dong, Guangbin (2014) Transition metal-catalyzed C-C bond activation of four-membered cyclic ketones. Top Curr Chem 346:233-57|
|Chen, Peng-Hao; Savage, Nikolas A; Dong, Guangbin (2014) Concise Synthesis of Functionalized Benzocyclobutenones. Tetrahedron 70:4135-4146|
|Xu, Tao; Dong, Guangbin (2014) Coupling of sterically hindered trisubstituted olefins and benzocyclobutenones by C-C activation: total synthesis and structural revision of cycloinumakiol. Angew Chem Int Ed Engl 53:10733-6|
|Ko, Haye Min; Dong, Guangbin (2014) Cooperative activation of cyclobutanones and olefins leads to bridged ring systems by a catalytic [4 + 2] coupling. Nat Chem 6:739-44|