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 #
1R01GM109054-01
Application #
8614748
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
2013-09-30
Budget End
2014-06-30
Support Year
1
Fiscal Year
2013
Total Cost
$286,094
Indirect Cost
$96,094
Name
University of Texas Austin
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
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
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
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
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
Zhou, Xuan; Dong, Guangbin (2015) (4+1) vs (4+2): Catalytic Intramolecular Coupling between Cyclobutanones and Trisubstituted Allenes via C-C Activation. J Am Chem Soc 137:13715-21
Lu, Gang; Fang, Cheng; Xu, Tao et al. (2015) Computational Study of Rh-Catalyzed Carboacylation of Olefins: Ligand-Promoted Rhodacycle Isomerization Enables Regioselective C-C Bond Functionalization of Benzocyclobutenones. J Am Chem Soc 137:8274-83
Whittaker, Rachel E; Dong, Guangbin (2015) Controlled Rh-Catalyzed Mono- and Double-decarbonylation of Alkynyl α-Diones To Form Conjugated Ynones and Disubstituted Alkynes. Org Lett 17:5504-7
Zhou, Xuan; Zafar, Imran; Dong, Guangbin (2015) Catalytic intramolecular decarbonylative coupling of 3-aminocyclobutenones and alkenes: a unique approach to [3.1.0] bicycles. Tetrahedron 71:4478-4483
Dermenci, Alpay; Whittaker, Rachel E; Gao, Yang et al. (2015) Rh-Catalyzed Decarbonylation of Conjugated Ynones via Carbon-Alkyne Bond Activation: Reaction Scope and Mechanistic Exploration via DFT Calculations. Chem Sci 6:3201-3210
Zeng, Rong; Dong, Guangbin (2015) Rh-Catalyzed decarbonylative coupling with alkynes via C-C activation of isatins. J Am Chem Soc 137:1408-11

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