Abigail Doyle

Abigail Doyle was born in NJ, Princeton in 1980 to Professor Michael W. Doyle and Dr. Amy Gutmann, the eighth president of the University of Pennsylvania. As an undergraduate, she studied both Chemistry and Chemical Biology at Harvard University and graduated with A.B. and A.M. degrees summa cum laude in 2002.

She then proceeded with her graduate studies at Stanford University. Shortly after, in 2003, she transferred to Harvard University and received her Ph.D there in transition metal-catalyzed enantioselective alkylations.

Early years

From May to August 2000, Doyle worked as an intern at Bristol Meyers Squibb. There, she studied the process aiding the preparation of type II diabetes treatment: Dapagliflozin.

Undergraduate years

During her undergraduate studies, she was part of Pfizer Summer Undergraduate Research Fellow at the American Chemistry Society (ACS). She also worked as an undergraduate research assistant at Harvard University. She worked with Dr. M. Christina White regarding the mechanism of a novel iron-catalyzed epoxidation reaction of terminal alkenes and designing chiral ligands for an asymmetric variant of the reaction.

Graduate years

She began her graduate career as a National Defense Science and Engineering (NDSEG) Fellow at the Dubois Laboratory at Stanford University, working on the preparation of Au(III) complexes and their reactivity for the hydration of unactivated alkenes. In September 2003, she transferred to Harvard University to continue her graduate work. She performed her Ph.D. work in the Jacobsen laboratory and worked alongside with Dr. Sarah Reisman. There she discovered an approach for the enantioselective addition of nucleophiles to oxocarbenium ions promoted by a thiourea catalyst. Doyle also co-authored a Chemical Review article on hydrogen-bond donor catalysis, which has received more than 1200 citations so far. Throughout her graduate years, she received the Harvard College Certificate of Distinction in Teaching as well as the Sigma-Aldrich Graduate Student Innovation Award and Christensen Prize for Outstanding Research Achievement.

Independent career

In July 2008, Doyle was appointed as an Assistant Professor of Chemistry at Princeton University. Doyle was promoted to the rank of Associate Professor with tenure in 2013. During her independent career at Princeton, her group identified catalytic cross-coupling reactions with styrenyl epoxides and aziridines as electrophiles and pioneered several other important transformations using Ni-based catalysts. Her recent collaborative work with MacMillan, identified a new cross-coupling paradigm which allows the combination of photoredox and nickel catalysis. Moreover, she identified a novel ligand class that showed unique electronic properties to a transition metal catalyst for cross-coupling catalysis. Such ligand showed great promise since it is able to be prepared from utilizing inexpensive and commercial components and be used to influence reaction rates and selectivity. Finally, group has been involved in the development of nucleophilic fluorination chemistry allowing to create pharmaceutically-relevant molecules with sp³-C-F and sp²-C-F bonds.

Figure 2: Copper-Catalyzed H-F Insertion Reaction Optimization Gray, E. E.; Nielsen, M. K.; Choquette, K. A.; Kalow, J. A.; Graham, T. J. A.; Doyle, A. G. Nucleophilic (Radio)Fluorination of α-Diazocarbonyl Compounds Enabled by Copper-Catalyzed H–F Insertion J. Am. Chem. Soc. 2016, 138, 10802−10805.

Figure 3: C-F Bond Formation by Pd (0)-Catalyzed Fluorination Katcher, M. H.; Norrby, P.-O.; Doyle, A. G. Mechanistic Investigations of Palladium-Catalyzed Allylic Fluorination. Organometallics. 2014, 33, 2121–2133.

Another on-going research the group is working on is Ni-catalyzed cross coupling. They aim to develop new cross-coupling reactions with classic aliphatic electrophiles in organic synthesis, which includes epoxides, aziridines, or acetals. As shown by the figure below, metallaphotoredox catalysis assisted by nickel mediates the C(sp³)-H acylation.

Figure 4: Ni-Catalyzed reaction of C(sp³)-H Cross-Coupling with Acyl Electrophiles Joe, C. L.; Doyle, A. G. Direct Acylation of C(sp³)−H Bonds Enabled by Nickel and Photoredox Catalysis Angew. Chem. Int. Ed. 2016, 55, 4040-4043

This may open up possibilities for a wide array of amines and ethers synthetic methods. Most importantly, it will allow rapid access to medicinal applications.

Phi Lambda Upsilon National Fresenius Award, Phi Lamba Upsilon, 2014

Presidential Early Career Award for Scientists and Engineers, PECASE, 2014

Novartis Chemistry Lectureship, 2014 and 2015

Bayer Early Excellence in Science Award, Bayer Foundations, 2013

Arthur C. Cope Scholar Award, American Chemical Society, 2013

Camille-Dreyfus Teacher Scholar Award, The Camille & Henry Dreyfus Foundation Inc., 2013

Thieme Chemistry Journals Award, Thieme Chemistry, 2013

Amgen Young Investigator Award, Amgen, 2012

Alfred P. Sloan Foundation Fellowship, Alfred P. Sloan Foundation, 2012

NSF CAREER Award, National Science Foundation, 2012–2017

Roche Early Excellence in Chemistry Award, 2012

Eli Lilly Grantee Award, 2012–2014

Boehringer Ingelheim New Investigator Award, Boehringer Ingelheim, 2012

Merck Award for Selective Fluorination, Princeton University, 2010–2012

ACS PRF Doctoral New Investigator Grant, American Chemical Society, 2009

Sanofi Aventis New Faculty Award, Princeton University, 2008

Eli Lilly New Faculty Award, Princeton University, 2008

Harvard Merit Fellowship, Harvard University, 2007

Sigma-Aldrich Graduate Student Innovation Award, 2006

Christensen Prize for Outstanding Research Achievement, Harvard University, 2005

National Science Foundation Pre-Doctoral Fellowship, NSF, 2004–07

National Defense Science and Engineering Pre-Doctoral Fellowship, NDSEG, 2002–2004

Harvard College Certificate of Distinction in Teaching, Harvard University, 2004

Phi Beta Kappa Junior Inductee, Yale University, 2001

Pfizer Undergraduate Summer Research Fellowship, 2001

Harvard College Research Fellowship Award, Harvard University, 2001

Harvard Detur Prize Recipient, Harvard University, 1999

Arendt, K. M.; Doyle, A. G. Dialkyl Ether Formation via Nickel-Catalyzed Cross Coupling of Acetals and Aryl Iodides. Angew. Chem. Int. Ed. 2015 DOI:10.1002/anie.201503936R1.

Huang, C.-Y.; Doyle, A. G. Electron-Deficient Olefin Ligands Enable Generation of Quaternary Carbons by Ni-Catalyzed Cross Coupling. J. Am. Chem. Soc. 2015, 137, 5638–5641.DOI: 10.1021/jacs.5b02503.

Shields, J. D.; Gray, E. E.; Doyle, A. G. A Modular, Air-Stable Nickel Precatalyst. Org. Lett. 2015, 17, 2166– 2169. DOI: 10.1021/acs.orglett.5b00766.

Zuo, Z.; Ahneman, D.; Chu, L.; Terrett, J.; Doyle, A. G.; MacMillan, D. W. C. Merging photoredox with nickel catalysis: Coupling of α-carboxyl sp3-carbons with aryl halides. Science 2014, 345, 437–440. DOI: 10.1126/science.1255525.

Huang, C.-Y. (Dennis); Doyle, A. G. The Chemistry of Transition Metals with Three-Membered Ring Heterocycles. Chem. Rev. 2014, 114, 8153–8198. DOI: 10.1021/cr500036t.

Graham, T. J.; Lambert, R. F.; Ploessl, K.; Kung, H. F.; Doyle, A. G. Enantioselective radiosynthesis of positron emission tomography (PET) tracers containing [¹⁸F]fluorohydrins. J. Am. Chem. Soc. 2014, 136, 5291-5294. DOI: 10.1021/ja5025645.

Shields, J. D.; Ahneman, D. T.; Graham, T. J. A.; Doyle, A. G. Enantioselective, Nickel-Catalyzed Suzuki Cross-CouplingofQuinoliniumIons.Org. Lett. 2013,16,142–145. DOI: 10.1021/ol4031364.

Nielsen, D. K.; Huang, C.-Y. (Dennis); Doyle, A. G. Directed Nickel-Catalyzed Negishi Cross Coupling of Alkyl Aziridines. J. Am. Chem. Soc. 2013, 135, 13605–13609. DOI: 10.1021/ja4076716.

Braun, M.-G.; Doyle, A. G. Palladium-Catalyzed Allylic C–H Fluorination. J. Am. Chem. Soc. 2013, 135, 12990–12993. DOI: 10.1021/ja407223g.

Chau, S. T.; Lutz, J. P.; Wu, K.; Doyle, A. G. Nickel-Catalyzed Enantioselective Arylation of Pyridinium Ions: Harnessing an Iminium Ion Activation Mode. Angew. Chem., Int. Ed. 2013, 52, 9153–9156. DOI: 10.1002/anie.201303994.

Braun, M.-G.; Katcher, M. H.; Doyle, A. G. Carbofluorination via a Palladium-Catalyzed Cascade Reaction. Chemical Science, 2013, 4, 1216–1220. DOI: 10.1039/C2SC22198E.

Sylvester, K. T.; Wu, K.; Doyle, A. G. Mechanistic Investigations of the Nickel-Catalyzed Suzuki Reaction of N,O-Acetals: Evidence for Boronic Acid-Assisted Oxidative Addition and an Iminium Activation Pathway. J. Am. Chem. Soc. 2012, 134, 16967–16970. DOI: 10.1021/ja3079362.

Kalow, J. A.; Schmitt, D. E.; Doyle, A. G. Synthesis of â-Fluoroamines by Lewis Base-Catalyzed Hydrofluorination of Aziridines. J. Org. Chem. 2012, 77, 4177–4183. DOI: 10.1021/jo300433a.

Huang, C.-Y. (Dennis); Doyle, A. G. Nickel-Catalyzed Negishi Alkylations of Styrenyl Aziridines. J. Am. Chem. Soc. 2012, 134, 9541–9544. DOI: 10.1021/ja3013825.

Graham, T. J. A.; Doyle, A. G. Nickel-Catalyzed Cross Coupling of Chromene Acetals and Boronic Acids. Org. Lett. 2012, 14, 1616–1619. DOI: 10.1021/ol300364s.

Katcher, M. H.; Sha, A.; Doyle, A. G. Regio- and Enantioselective Fluorination of Acyclic Allylic Halides. J. Am. Chem. Soc. 2011, 133, 15902–15905. DOI: 10.1021/ja206960k.

Kalow, J. A.; Doyle, A. G. Mechanistic Investigations of Cooperative Catalysis in the Enantioselective Fluorination of Epoxides. J. Am. Chem. Soc. 2011, 133, 16001–16012. DOI: 10.1021/ja207256s.

Graham, T. J. A.; Doyle, A. G. Transition Metal-Catalyzed Cross Coupling with N-Acyliminium Ions Derived from Quinolines and Isoquinolines. Chem. Sci. 2011, 2, 980–984. DOI: 10.1039/C1SC00026H.

Katcher, M. H.; Doyle, A. G. Palladium-Catalyzed Asymmetric Synthesis of Allylic Fluorides. J. Am. Chem. Soc. 2010, 132, 17402–17404. DOI: 10.1021/ja109120n.