The development of powerful new methods for the generation of carbon-carbon bonds has an impact on a wide array of disciplines that require the synthesis of organic compounds (e.g., biological chemistry, pharmaceutical chemistry, and biology). Transition metals can catalyze carbon-carbon bond-forming processes, such as cross-couplings of organic electrophiles and nucleophiles, that would otherwise be difficult or impossible to achieve. During the next grant period, this program will pursue a largely unexplored dimension of cross-coupling reactions-processes that employ alkyl electrophiles as substrates. Efforts will focus on the development of versatile catalysts, including chiral catalysts, for a wide range of powerful bond-forming processes. Such reactions have the potential to simultaneously generate a carbon-carbon bond and to define up to two new stereocenters. Mechanistic studies will play an important role in this project, since an improved understanding of metal-based reactivity could facilitate catalyst development. This research area offers an exciting opportunity to have a substantial impact on synthetic chemistry, as well as to enrich our understanding of once-unexpected chemical reactivity.

Public Health Relevance

In order to probe many biological questions and to develop new therapeutic compounds, there is a need to be able to synthesize organic molecules efficiently and to control the chirality (handedness) of the target compounds. This proposal is directed at addressing both of these challenges.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Method to Extend Research in Time (MERIT) Award (R37)
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Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Lees, Robert G
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California Institute of Technology
Schools of Engineering
United States
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Zuo, Zhiwei; Cong, Huan; Li, Wei et al. (2016) Enantioselective Decarboxylative Arylation of α-Amino Acids via the Merger of Photoredox and Nickel Catalysis. J Am Chem Soc 138:1832-5
Chu, Crystal K; Liang, Yufan; Fu, Gregory C (2016) Silicon-Carbon Bond Formation via Nickel-Catalyzed Cross-Coupling of Silicon Nucleophiles with Unactivated Secondary and Tertiary Alkyl Electrophiles. J Am Chem Soc 138:6404-7
Liang, Yufan; Fu, Gregory C (2015) Nickel-Catalyzed Alkyl-Alkyl Cross-Couplings of Fluorinated Secondary Electrophiles: A General Approach to the Synthesis of Compounds having a Perfluoroalkyl Substituent. Angew Chem Int Ed Engl 54:9047-51
Liang, Yufan; Fu, Gregory C (2015) Stereoconvergent Negishi Arylations of Racemic Secondary Alkyl Electrophiles: Differentiating between a CF3 and an Alkyl Group. J Am Chem Soc 137:9523-6
Schley, Nathan D; Fu, Gregory C (2014) Nickel-catalyzed Negishi arylations of propargylic bromides: a mechanistic investigation. J Am Chem Soc 136:16588-93
Liang, Yufan; Fu, Gregory C (2014) Catalytic asymmetric synthesis of tertiary alkyl fluorides: Negishi cross-couplings of racemic α,α-dihaloketones. J Am Chem Soc 136:5520-4
Choi, Junwon; Martín-Gago, Pablo; Fu, Gregory C (2014) Stereoconvergent arylations and alkenylations of unactivated alkyl electrophiles: catalytic enantioselective synthesis of secondary sulfonamides and sulfones. J Am Chem Soc 136:12161-5
Cong, Huan; Fu, Gregory C (2014) Catalytic enantioselective cyclization/cross-coupling with alkyl electrophiles. J Am Chem Soc 136:3788-91
Cordier, Christopher J; Lundgren, Rylan J; Fu, Gregory C (2013) Enantioconvergent cross-couplings of racemic alkylmetal reagents with unactivated secondary alkyl electrophiles: catalytic asymmetric Negishi α-alkylations of N-Boc-pyrrolidine. J Am Chem Soc 135:10946-9
Zultanski, Susan L; Fu, Gregory C (2013) Nickel-catalyzed carbon-carbon bond-forming reactions of unactivated tertiary alkyl halides: Suzuki arylations. J Am Chem Soc 135:624-7

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