Seminar: Dr Sinead Keaveney - Development of novel transition-metal catalysed chemical transformations to access high value target compounds

Thursday, 15 November 2018 - 12:00pm – Thursday, 15 November 2018 - 1:00pm  |  CHEMSCI M17

Speaker: Dr Sinead Keaveney

Transition metal catalysis is a well-known strategy to promote complex and selective chemical transformations under relatively mild conditions. However, many challenges in this field still remain; this presentation focuses on developing novel chemical transformations, with emphasis on processes that are amenable to industrial scale synthesis.

Firstly, fluorine-containing functional groups can significantly impact compound potency, with 25% of pharmaceuticals and 40% of agrochemicals featuring fluorine. The trifluoromethyl group is particularly useful, however, introducing CFvia Pd(0)/Pd(II) catalysis is very challenging due to the difficult transmetalation and reductive elimination steps.We overcame these challenges by developing the first protocol to convert acid fluorides to aryl-CF3, with the key Pd(II)-F intermediate facilitating selective and additive-free transmetalation.2

Secondly, to meet the increasing demands for diverse compound libraries, highly modular and streamlined approaches to assemble densely functionalized arenes are desired. Historically, chemoselectivity in Pd(0) catalyzed functionalisations of poly(pseudo)halogenated arenes has been unpredictable, being dependent on the catalyst, conditions and substrate. However, this issue has been solved through use of a single air-stable Pd(I) dimer for the first sequential functionalisation procedure, with general C-Br,then C-OTf, then C-Cl cross-coupling achieved in <40 min.4

 Lastly, initial studies and future work on the development of more efficient and sustainable chemical processes through use of hybrid homogeneous-heterogenous catalysts will be presented.5

 

[1] V. V. Grushin, W. J. Marshall, J. Am. Chem. Soc. 2006128, 4632; V. V. Grushin, W. J. Marshall, J. Am. Chem. Soc. 2006128, 12644; Tomashenko, O. A.; Grushin, V. V., Chem. Rev. 2011, 111, 4475; M. C. Nielsen, K. J. Bonney, F. Schoenebeck, Angew. Chem. Int. Ed. 201453, 5903

[2] Keaveney, S. T.; Schoenebeck, F., Angew. Chem. Int. Ed. 2018, 57, 4073

[3] Kalvet, I.; Magnin, G.; Schoenebeck, F., Angew. Chem. Int. Ed. 2017, 56, 1581 

[4] Keaveney, S. T.; Kundu, G.; Schoenebeck, F., Angew. Chem. Int. Ed. 2018, 57, 12573  

[5] Keaveney, S. T.; Pernik, I.; Messerle, B. A., ongoing work