Arylation reaction fails ascorbic acid test | Chemical & Engineering News
Volume 94 Issue 28 | p. 10 | Concentrates
Issue Date: July 11, 2016

Arylation reaction fails ascorbic acid test

Chemists find that the reducing agent is not automatically necessary as a promoter in organic reactions
Department: Science & Technology
News Channels: Organic SCENE
Keywords: ascorbic acid, reducing agent, retraction

Ascorbic acid is familiar to many organic chemists as a useful reducing agent to help promote reactions. For example, researchers have thought that ascorbic acid is needed in conjunction with tert-butyl nitrite to carry out C–H activation and radical arylation of heterocyclic N-oxides to make biaryl compounds. Richard A. J. Horan of GlaxoSmithKline and coworkers published a paper in Organic Process Research & Development last year expanding on the selective metal-free coupling reaction. But it wasn’t until the researchers later ran control experiments omitting ascorbic acid as part of their ongoing investigations that they discovered they could get the same results without it. “This was a complete surprise, as ascorbic acid is a well-precedented additive,” Horan says. “As a result, we thought it appropriate to retract our paper at the galley proof stage and investigate the mechanism in greater depth” (Org. Process Res. Dev. 2015, DOI: 10.1021/acs.oprd.5b00231). The team has now published a new version of the paper, with a warning for fellow chemists to not take the role of ascorbic acid for granted (Org. Process Res. Dev. 2016, DOI: 10.1021/acs.oprd.6b00117). “This has highlighted the importance of mechanistic understanding in organic chemistry, and we hope that our work will encourage further research in this area,” Horan says. “In my mind, this case shows how science should work,” adds Kai Rossen, a research director at Sanofi and editor-in-chief of OPR&D. “The next question will be how the common assumptions about this chemistry will be corrected.”

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Contrary to previous assumptions, ascorbic acid isn’t needed to promote this cross-coupling reaction.
Reaction scheme shows cross-coupling of aniline and a heterocyclic ╚N╚-oxide to make a biaryl compound.
 
Contrary to previous assumptions, ascorbic acid isn’t needed to promote this cross-coupling reaction.
 
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