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
Catalyst-controlled doubly enantioconvergent coupling of racemic alkyl nucleophiles and electrophiles
Huo, H.; Gorsline, B. J.; Fu, G. C.
Science 2020, 367, 559–564.
Catalytic enantioconvergent coupling of secondary and tertiary electrophiles with olefins
Wang, Z.; Yin, H.; Fu, G. C.
Nature, 2018, 563, 379–383.
Control of Vicinal Stereocenters through Nickel-Catalyzed Alkyl-Alkyl Cross-Coupling
Mu, X.; Shibata, Y.; Makida, Y.; Fu, G. C.
Angew. Chem. Int. Ed., 2017, 56, 5821–5824.
A general, modular method for the catalytic asymmetric synthesis of alkylboronate esters
Schmidt, J.; Choi, J.; Liu, A. T.; Slusarczyk, M.; Fu, G. C.
Science, 2016, 354, 1265–1269.
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
Design of a Photoredox Catalyst that Enables the Direct Synthesis of Carbamate-Protected Primary Amines via Photoinduced, Copper-Catalyzed N-Alkylation Reactions of Unactivated Secondary Halides
Ahn, J. M.; Peters, J. C.; Fu, G. C.
J. Am. Chem. Soc., 2017, 139, 18101–18106.
Copper-Catalyzed Alkylation of Aliphatic Amines Induced by Visible Light
Matier, C. D.; Schwaben, J.; Peters, J. C.; Fu, G. C.
J. Am. Chem. Soc., 2017, 139, 17707–17710.
Photoinduced,Copper-Catalyzed Decarboxylative C–N Coupling to Generate Protected Amines: An Alternative to the Curtius Rearrangement
Zhao, W.; Wurz, R. P.; Peters, J. P.; Fu, G. C.
J. Am. Chem. Soc., 2017, 139, 12153–12156.
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.