The construction of pharmaceutical and bioactive molecules relies on methods for the formation of carbon-carbon bonds. Over the past decade olefin metathesis has emerged as a powerful means by which to form these bonds in applications ranging from, but not limited to, small organic molecules, complex natural products, and well-controlled polymer architectures. The availability of robust catalysts that are highly active, efficient, stable, and selective is key to the further development of these wide-ranging applications. Over the last granting period catalysts were prepared that facilitate metathesis (a) in aqueous solutions, (b) with sterically hindered substrates, (c) at lower catalyst loadings, and (d) with higher levels of enantioselectivity. A powerfully simple method for the construction of N-heterocyclic carbene ligands was developed. This method will be exploited over the next granting period for the development of stereoselective metathesis catalysts (controlling the trans:cis ratio of the carbon-carbon double bonds), and improvement of catalyst stability (to lower catalyst loadings), among other proposed improvements. The design and preparation of such catalysts would further enable the rapid and selective formation of biologically-relevant chemical compounds.

Public Health Relevance

The preparation of bioactive molecules remains a significant challenge in the study of human health and related fields. Olefin metathesis is now routinely used for the constructions of such molecules. Development of catalysts for this reaction is key to the advancement of this powerful carbon-carbon bond forming technology.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Lees, Robert G
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
California Institute of Technology
Schools of Engineering
United States
Zip Code
Ogba, O M; Warner, N C; O'Leary, D J et al. (2018) Recent advances in ruthenium-based olefin metathesis. Chem Soc Rev 47:4510-4544
Ahmed, Tonia S; Montgomery, T Patrick; Grubbs, Robert H (2018) Using stereoretention for the synthesis of E-macrocycles with ruthenium-based olefin metathesis catalysts. Chem Sci 9:3580-3583
Ahmed, Tonia S; Grubbs, Robert H (2017) A Highly Efficient Synthesis of Z-Macrocycles Using Stereoretentive, Ruthenium-Based Metathesis Catalysts. Angew Chem Int Ed Engl 56:11213-11216
Martin, David; Marx, Vanessa M; Grubbs, Robert H et al. (2016) A Ruthenium Catalyst for Olefin Metathesis Featuring an Anti-Bredt N-Heterocyclic Carbene Ligand. Adv Synth Catal 358:965-969
Dornan, Peter K; Lee, Daniel; Grubbs, Robert H (2016) Tandem Olefin Metathesis/Oxidative Cyclization: Synthesis of Tetrahydrofuran Diols from Simple Olefins. J Am Chem Soc 138:6372-5
Rosebrugh, L E; Ahmed, T S; Marx, V M et al. (2016) Probing Stereoselectivity in Ring-Opening Metathesis Polymerization Mediated by Cyclometalated Ruthenium-Based Catalysts: A Combined Experimental and Computational Study. J Am Chem Soc 138:1394-405
Li, Jiaming; Grubbs, Robert H; Stoltz, Brian M (2016) Palladium-Catalyzed Aerobic Intramolecular Aminoacetoxylation of Alkenes Enabled by Catalytic Nitrate. Org Lett 18:5449-5451
Endo, Koji; Grubbs, Robert H (2016) Cationic ruthenium alkylidene catalysts bearing phosphine ligands. Dalton Trans 45:3627-34
Marx, Vanessa M; Sullivan, Alexandra H; Melaimi, Mohand et al. (2015) Cyclic alkyl amino carbene (CAAC) ruthenium complexes as remarkably active catalysts for ethenolysis. Angew Chem Int Ed Engl 54:1919-23
Tang, Grace Y; Pribisko, Melanie A; Henning, Ryan K et al. (2015) An in vitro enzymatic assay to measure transcription inhibition by gallium(III) and H3 5,10,15-tris(pentafluorophenyl)corroles. J Vis Exp :

Showing the most recent 10 out of 69 publications