Despite the tremendous accomplishments that have been described in the development of metal-catalyzed cross-couplings to form carbon–carbon bonds (as exemplified by the Nobel Prize in Chemistry in 2010), it is nevertheless true that many significant opportunities remain. For example, to date the overwhelming majority of studies have focused on couplings between two sp2-hybridized reaction sites (e.g., an aryl metal with an aryl halide). On the other hand, until recently there were relatively few examples of metal-catalyzed coupling reactions of alkyl electrophiles. To address this shortcoming, we are pursuing the discovery of metal-based catalysts for coupling a wide range of alkyl electrophiles, including enantioconvergent reactions of racemic electrophiles. Mechanistic studies are a significant component of this program.
Selected recent publications
Stereoconvergent Negishi Arylations of Racemic Secondary Alkyl Electrophiles: Differentiating between a CF3 and an Alkyl Group
Liang, Y.; Fu, G. C.
J. Am. Chem. Soc. 2015, 137, 9523–9526.
Nickel-Catalyzed Negishi Arylations of Propargylic Bromides: A Mechanistic Investigation
Schley, N. D.; Fu, G. C.
J. Am. Chem. Soc. 2014, 136, 16588–16593.
Nickel-Catalyzed Carbon–Carbon Bond-Forming Reactions of Unactivated Tertiary Alkyl Halides: Suzuki Arylations
Zultanski, S.; Fu, G. C.
J. Am. Chem. Soc. 2013, 135, 624–627.
Catalytic Enantioselective Cross-Couplings of Secondary Alkyl Electrophiles with Secondary Alkylmetal Nucleophiles: Negishi Reactions of Racemic Benzylic Bromides with Achiral Alkylzinc Reagents
Binder, J. T.; Cordier, C. J.; Fu, G. C.
J. Am. Chem. Soc. 2012, 134, 17003–17006.
Although the alkylation of an amine with an alkyl halide is one of the first reactions of amines that is taught in introductory textbooks on organic chemistry, there have been few studies of transition-metal catalysis of this transformation. In collaboration with the Peters lab at Caltech, we are pursuing the use of light and a transition-metal catalyst to achieve a wide range of couplings of heteroatom nucleophiles, including nitrogen nucleophiles, with alkyl electrophiles; in contrast to most photoredox catalysis, we employ a single catalyst for the key photochemistry and bond-forming processes. Enantioconvergent reactions of racemic alkyl halides, as well as mechanistic studies, are being investigated.
Selected recent publications
Asymmetric copper-catalyzed C–N cross-couplings induced by visible light
Kainz, Q. M.; Matier, C. D.; Bartoszewicz, A.; Zultanski, S. L.; Peters, J.C.; Fu, G. C.
Science 2016, 351, 681–684.
Photoinduced, Copper-Catalyzed Carbon–Carbon Bond Formation with Alkyl Electrophiles: Cyanation of Unactivated Secondary Alkyl Chlorides at Room Temperature
Ratani, T. S.; Bachman, S.; Fu, G. C.; Peters, J. C.
J. Am. Chem. Soc. 2015, 137, 13902–13907.
Oxygen Nucleophiles as Reaction Partners in Photoinduced, Copper-Catalyzed Cross-Couplings: O-Arylations of Phenols at Room Temperature
Tan, Y.; Muñoz-Molina, J. M.; Fu, G. C.; Peters, J. C.
Chem. Sci. 2014, 5, 2831–3835.
Photoinduced, Copper-Catalyzed Alkylation of Amides with Unactivated Secondary Alkyl Halides at Room Temperature
Do, H.-Q.; Bachman, S.; Bissember, A. C.; Peters, J. C.; Fu, G. C.
J. Am. Chem. Soc. 2014, 136, 2162–2167.