Graduate student Ryan Charlton will present
"Fe(III)-Catalyzed Carbonyl-Olefin Metathesis: Development, Application, and Mechanism"
on October 3, 2017 at 4:10 PM in Neville Hall, Room 3.
Recent work by the Schindler lab found that catalytic Fe(III) is capable of promoting carbonyl olefin metathesis, which offers great synthetic potential in its ability to generate a wide variety of carbon-carbon double bonds. Traditional olefin metathesis requires an expensive metal catalyst (often Mo or Ru), and two alkenyl moieties for reactivity. In this new Fe(III)-catalyzed methodology one of the reactive alkenes is replaced by a carbonyl, thereby greatly expanding the substrate scope of metathesis chemistry.
Prior to the discovery of Fe(III) catalysis, carbonyl-olefin metathesis required stoichiometric amounts of Mo- or Ti-alkylidene complexes. Initial investigations examined the effect of Lewis acids on promoting the intramolecular carbonyl-olefin metathesis to generate substituted cyclopentenes. Of the Lewis acides explored, FeCl3 was uniquely effective at promoting the desired chemistry. Further investigation found that the reaction tolerated electron-poor and electron-rich functionality, alongside halogenations, to provide products in 64-99% yields. In contracts to traditional olefin metathesis, this Fe(III)-catalyzed process is less sterically-sensitive, capable of generating tetrasubstituted olefin products and cyclic olefins adjacent to quaternary carbon centers. Preliminary mechanistic studies suggested that the transformation proceeds through a Fe- coordinated oxetane, and not through carbonation intermediates.
In order to expand the utility of the methodology, carbonyl-olefin metathesis was explored as a strategy for synthesizing complex polycyclic aromatic hydrocarbons. Such a strategy complements the previously reported strategies that use bis-carbonyl starting materials like McMurray couplings, hydrazone dimerization, or Ru-catalyzed olefin metathesis. Polyarenes substituted with a ketone and olefin were explored as substrates that upon metathesis generate a fused polycycle via six-membered ring formation. Aside from competing carbonyl-ene side reactions, the transformation was found to be robust, functional group tolerant, and effective for generating carious polycyclic aromatic products (over 35 examples) in yields up to 99%.
Recent mechanistic studies have tried to more accurately deduce how carbonyl-olefin metathesis occurs. Catalytic studies and EPR experiments support Fe(III) initially binding to a carbonyl oxygen atom. Theoretical modeling and kinetic studies then suggest that oxetane formation occurs or stepwise fashion to give the product olefin. It is through this metal-catalyzed process that carbonyl-olefin metathesis is able to achieve such novel selectivity and reactivity.
- Ludwig, J., Phan, S., McAtee, C., Zimmerman, P., Devery, III, J., and Schindler, C. J. Am Chem. Soc. 2017 139(31) 10832-10842
- McAtee, C., Riehl, P., and Schindler, C. J. Am Chem. Soc. 2017 139 (8) 2960-2963
- Ludwig, J., Zimmerman, P., Gianino, J., and Schindler, C. Nature 2016 533 374-379