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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM109054-02
Application #
8744633
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Lees, Robert G
Project Start
2013-09-30
Project End
2018-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Texas Austin
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
City
Austin
State
TX
Country
United States
Zip Code
78712
Xia, Ying; Wang, Jianbo; Dong, Guangbin (2017) Distal-Bond-Selective C-C Activation of Ring-Fused Cyclopentanones: An Efficient Access to Spiroindanones. Angew Chem Int Ed Engl 56:2376-2380
Chen, Peng-Hao; Billett, Brent A; Tsukamoto, Tatsuhiro et al. (2017) ""Cut and Sew"" Transformations via Transition-Metal-Catalyzed Carbon-Carbon Bond Activation. ACS Catal 7:1340-1360
Xia, Ying; Lu, Gang; Liu, Peng et al. (2016) Catalytic activation of carbon-carbon bonds in cyclopentanones. Nature 539:546-550
Zhou, Xuan; Dong, Guangbin (2016) Nickel-Catalyzed Chemo- and Enantioselective Coupling between Cyclobutanones and Allenes: Rapid Synthesis of [3.2.2] Bicycles. Angew Chem Int Ed Engl 55:15091-15095
Zhou, Xuan; Ko, Haye Min; Dong, Guangbin (2016) Synthesis of Bridged Cyclopentane Derivatives by Catalytic Decarbonylative Cycloaddition of Cyclobutanones and Olefins. Angew Chem Int Ed Engl 55:13867-13871
Zeng, Rong; Chen, Peng-Hao; Dong, Guangbin (2016) Efficient Benzimidazolidinone Synthesis via Rhodium-Catalyzed Double-Decarbonylative C-C Activation/Cycloaddition between Isatins and Isocyanates. ACS Catal 6:969-973
Chen, Peng-Hao; Dong, Guangbin (2016) Cyclobutenones and Benzocyclobutenones: Versatile Synthons in Organic Synthesis. Chemistry 22:18290-18315
Deng, Lin; Xu, Tao; Li, Hongbo et al. (2016) Enantioselective Rh-Catalyzed Carboacylation of C?N Bonds via C-C Activation of Benzocyclobutenones. J Am Chem Soc 138:369-74
Chen, Peng-Hao; Sieber, Joshua; Senanayake, Chris H et al. (2015) Rh-catalyzed Reagent-Free Ring Expansion of Cyclobutenones and Benzocyclobutenones. Chem Sci 6:5440-5445
Whittaker, Rachel E; Dong, Guangbin (2015) Controlled Rh-Catalyzed Mono- and Double-decarbonylation of Alkynyl ?-Diones To Form Conjugated Ynones and Disubstituted Alkynes. Org Lett 17:5504-7

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