Electroreductive Olefin-Ketone Coupling
Pengfei Hu, Byron K. Peters, Christian A. Malapit, Julien C. Vantourout, Pan Wang, Jinjun Li, Lucas Mele, Pierre-Georges Echeverria, Shelley D. Minteer* and Phil S. Baran*
*NSF Center for Synthetic Organic Electrochemistry, University of Utah, 315 South 1400 East, Salt Lake City 84112, Utah, United States, Email: minteerchem.utah.edu, pbaranscripps.edu
P. Hu, B. K. Peters, C. A. Malapit, J. C. Vantourout, P. Wang, J. Li, L. Mele, P.-G. Echeverria, S. D. Minteer, P. S. Baran, J. Am. Chem. Soc., 2020, 142, 20979-20986.
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Using an electrochemical approach, a ketone acts as a nucleophile when adding to simple unactivated olefins to accomplish an overall transformation similiar to a Grignard addition to unactivated ketones to access tertiary alcohols. This coupling offers a broad reaction scope, is scalable, chemoselective, and requires no precaution to exclude air or water.
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General Procedures for Electro-Reductive Ketone-Olefin Coupling
Setup: IKA Zn (anode) and Sn (cathode) plate electrodes or home-made ones from the corresponding metal wires were connected to an ElectraSyn vial cap. A standard 2-mL ElectraSyn vial was charged a magnetic stirrer bar, nBu4NBr (96.7mg, 0.3 mmol), ketone (0.7 mmol), olefin (0.35 mmol) and DMF (1 mL). The cap was installed and the vial was pre-stirred until all solids dissolved. Then, it was fit into the ElectraSyn and the following setup was employed: New exp. ➞ Constant current ➞ 10 mA ➞ No ref. electrode ➞ Total charge ➞ 0.35 mmol, 5 F/mol (see individual compounds) ➞ No alternating polarity ➞ start. After completion, the reaction mixture was passed through a short plug of silica gel and washed with EtOAc (20 mL). The solution was further purified via column chromatography to give the desired product. Both cathode and sacrificial anode can be easily cleaned and reused without impact on the reaction yield.
The reaction time is about 4.5 hours on 0.35 mmol scale. The reaction time depends on the reaction scale and is roughly 10 hours/mmol.
Phil S. Baran, August 18, 2021