Seminar
Tuesday, October 3, 2017 - 12:00am
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.
Abstract:
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.
References:
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