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.
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.
|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 *-alkylations of N-Boc-pyrrolidine. J Am Chem Soc 135:10946-9|
|Do, Hien-Quang; Chandrashekar, E R R; Fu, Gregory C (2013) Nickel/bis(oxazoline)-catalyzed asymmetric Negishi arylations of racemic secondary benzylic electrophiles to generate enantioenriched 1,1-diarylalkanes. J Am Chem Soc 135:16288-91|
|Lundin, Pamela M; Fu, Gregory C (2010) Asymmetric Suzuki cross-couplings of activated secondary alkyl electrophiles: arylations of racemic alpha-chloroamides. J Am Chem Soc 132:11027-9|
|Lou, Sha; Fu, Gregory C (2010) Pd/P(t-Bu)(3)-Catalyzed Suzuki Cross-Couplings in the Presence of Water. Adv Synth Catal 352:2081-2084|
|Owston, Nathan A; Fu, Gregory C (2010) Asymmetric alkyl-alkyl cross-couplings of unactivated secondary alkyl electrophiles: stereoconvergent Suzuki reactions of racemic acylated halohydrins. J Am Chem Soc 132:11908-9|