Electro-reductive Halogen-Deuterium Exchange and Methylation of Aryl Halides in Acetonitrile

Abstract

An electro-reductive halogen-deuterium exchange reaction in CD 3 CN has been developed. Using 9-fluorenone as a mediator, the electro-reduction of several aryl halides proceeded smoothly to give the deuterated products selectively. A methylation reaction of aryl halides also proceeded under similar conditions.

Synthetic Organic Electrochemical Methods Since 2000: On the Verge of a Renaissance

“…734 MeCN putatively provides the methyl group under electrolytic conditions while the deuterated product was formed in a smaller proportion. Intriguingly, when an aryl chloride was used, the reductive dehalogenation pathway predominated.…”

Current electrochemical approaches to selective deuteration

“…43 In more recent years, Suga demonstrated the use of a fluorenone redox mediator for the reductive deuteration of aryl halides. 44 In this case, deuterium was delivered from d 3 -MeCN, however with some methylation by-products.…”

Electrocatalytic Deuteration of Halides with D2O as the Deuterium Source over a Copper Nanowire Arrays Cathode

“…Despite effectiveness, the typical metal‐halogen exchange or transition‐metal‐catalyzed processes always use noble metal catalysts with complex ligands, special deuterium donors, and highly active alkyl‐metal reagents under anaerobic and cryogenic conditions, retarding their practical applications . Whereas radical reductive deuteration of halides usually suffers from the photocorrosion‐induced instability of photocatalysts, concurrent side reactions of sacrificial agents, and low deuterated efficiency for less activated bromides due to the narrow redox‐potential window . Therefore, developing a general and mild method for efficient deuterium incorporation with broad substrate scopes, precise deuterated sites and amounts, and excellent deuterium purity is highly desirable.…”

“…Thus, it is reasonable and extremely urgent to develop electrochemical organic reduction reactions using the in situ formed *H as a strong reducing agent, which is far from being fully developed . Despite the important advance was achieved in the electrocatalytic dehalogenative deuteration of aryl halides, a large amount of expensive CD 3 CN, the high‐cost electrolyte, and the organic additive were required in the pure organic solvent with a few substrate cases and the unclear mechanism.…”

“…Our strategy was applied well to the deuteration of less‐active bromides (Table , 2 k – 4 d ), which usually give low efficiency by current radical reductive methods . Owing to the mild reaction conditions and the catalytic specificity of Cu NWAs cathodes, other reducible functional groups commonly presented in pharmaceuticals (such as C≡N, C≡C, C=C, C=O, and C=N) could be retained well, providing rich opportunities for downstream fabrication of complex deuterated molecules (Table , 2 k – 2 o ).…”