Brandon Ashfeld // People // Department of Chemistry & Biochemistry // University of Notre Dame

Brandon Ashfeld

Synthetic Organic Chemistry Transition Metal Catalysis in Synthetic Methods Development

Biography

2014-present: Associate Professor, University of Notre Dame
2016-present: Director of Graduate Studies, University of Notre Dame
2007-2014: Assistant Professor, University of Notre Dame
2004-2007: Ruth L. Kirschstein NIH Postdoctoral Fellow, Stanford University
2004: Ph.D. in Chemistry, University of Texas at Austin
1998: B.S. in Chemistry, University of Minnesota-Twin Cities

Selected Awards

2015: Rev. Edmund P. Joyce, C.S.C. Award for Excellence in Undergraduate Teaching
2011: NSF CAREER Award
2009: University of Notre Dame Faculty Scholarship Award

Research Interests

Our research program is focused on the development of new methods to enable unconventional bond formations in the synthesis of complex natural products and designed materials. Our main objective is to use new chemical constructs to design and synthesize improved chemotherapies for brain and CNS cancers, and materials that will ultimately lead to the reduction of atmospheric concentrations of anthropogenic CO₂.

Designing Brain and CNS Cancer Chemotherapeutics.

We seek to addresses the issue of suitable brain and CNS drug treatment options by focusing on natural products with promising cytotoxicity that also display blood brain barrier (BBB) transcytosis properties. Specifically, the families of diarylheptanoids and glycosidic marine toxin natural products have captured our attention due to the potent anticancer activity exhibited by multiple members of each class. We are currently working toward the development of two new synthetic methods that will enable the efficient, and scalable construction of these natural products for the development of new CNS cancer chemotherapeutics. The first approach is based on the conceptual design of a tandem reaction sequence composed of mechanistically distinct transformations facilitated by a single catalyst to rapidly assemble all alkyl-substituted tertiary carbons centers. By exploiting aldehydes as traceless dielectrophilic entities, in conjunction with the bifunctional attributes of titanocene, we can construct multiple C–C and C–X bonds in a highly convergent fragment coupling. Our second area of methods development focuses on the formation of Csp²–N and Csp²–C bonds, which constitutes one of the most vibrant areas of research in synthetic organic chemistry today. Unfortunately, conventional multistep protocols involving organometallic reagents and transition metal complexes can complicate complex molecule synthesis. Our program is working toward providing a solution to this long-standing problem in organic synthesis through the development phosphorus-mediated C–C and C–N bond formations that ultimately circumvents the need for traditional organometallic or transition metal-based reagents.

Innovating the Chemistry of Covalent Carbon Capture.

Managing the impact of human activities on the concentration of CO₂ in the atmosphere is the most far-reaching environmental challenge facing the world today. Carbon capture and separation is an integral part of our energy future, independent of its application to today’s coal-fired power plants. Our research program is working toward the development of a strategy to control atmospheric, anthropogenic CO₂ concentrations through the design of energy efficient carbon capture and sequestration materials. Our ultimate goal is the development of a regenerative material that will undergo selective super-stoichiometric carbon capture with near-zero parasitic energy consumption. Recognizing that C–C and C–X chemical bonds are convenient media for energy storage, transport, and consumption, our efforts rely on the design and synthesis of functionalized N-heterocyclic anions and carbenes for energy efficient gas phase removal of CO₂.

Recent Papers

Eckert, K.E., Ashfeld, B.L. "Aroyl Isocyanates as 1,4-Dipoles in a Formal [4 + 1]-Cycloaddition Approach toward Oxazolone Construction" 2018 Organic Letters, 20 (8), pp. 2315-2319. DOI: 10.1021/acs.orglett.8b00656
Rodriguez, K.X., Pilato, T.C., Ashfeld, B.L. "An unusual stereoretentive 1,3-quaternary carbon shift resulting in an enantioselective RhII-catalyzed formal [4+1]-cycloaddition between diazo compounds and vinyl ketenes" 2018 Chemical Science, 9 (12), pp. 3221-3226. DOI: 10.1039/c8sc00020d
Schnepp, P.M., Lee, D.D., Guldner, I.H., O'Tighearnaigh, T.K., Howe, E.N., Palakurthi, B., Eckert, K.E., Toni, T.A., Ashfeld, B.L., Zhang, S. "GAD1 upregulation programs aggressive features of cancer cell metabolism in the brain metastatic microenvironment" 2017 Cancer Research, 77 (11), pp. 2844-2856. DOI: 10.1158/0008-5472.CAN-16-2289
Rodriguez, K.X., Kaltwasser, N., Toni, T.A., Ashfeld, B.L. "Rearrangement of an Intermediate Cyclopropyl Ketene in a RhII-Catalyzed Formal [4 + 1]-Cycloaddition Employing Vinyl Ketenes as 1,4-Dipoles and Donor-Acceptor Metallocarbenes" 2017 Organic Letters, 19 (10), pp. 2482-2485. DOI: 10.1021/acs.orglett.7b00618
Meloche, J.L., Ashfeld, B.L. "A Rhodium(II)-Catalyzed Formal [4+1]-Cycloaddition toward Spirooxindole Pyrrolone Construction Employing Vinyl Isocyanates as 1,4-Dipoles" 2017 Angewandte Chemie - International Edition, 56 (23), pp. 6604-6608. DOI: 10.1002/anie.201701147
Rodriguez, K.X., Vail, J.D., Ashfeld, B.L. "Phosphorus(III)-Mediated Stereoconvergent Formal [4+1]-Cycloannulation of 1,2-Dicarbonyls and o-Quinone Methides: A Multicomponent Assembly of 2,3-Dihydrobenzofurans" 2016 Organic Letters, 18 (18), pp. 4514-4517. DOI: 10.1021/acs.orglett.6b02122