{"id":548486,"date":"2026-06-22T16:06:16","date_gmt":"2026-06-22T16:06:16","guid":{"rendered":"https:\/\/www.europesays.com\/ie\/548486\/"},"modified":"2026-06-22T16:06:16","modified_gmt":"2026-06-22T16:06:16","slug":"cross-coupling-preserves-stereochemistry-of-chiral-carboxylic-acids","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/ie\/548486\/","title":{"rendered":"Cross-coupling preserves stereochemistry of chiral carboxylic acids"},"content":{"rendered":"

\u00a0<\/p>\n

Synthetic organic chemists love their cross-coupling reactions, in which they quickly construct a complex compound by connecting two different, simpler structures. Building bonds of this type between two sp3 carbons has been a hot area of research<\/a>, particularly if it can be done in a way that makes the new molecule as a single stereoisomer. Chemists report a new alkyl-alkyl cross-coupling reaction<\/a> that keeps the stereochemistry of one of the coupling partners intact through what the research team behind it describes as a \u201cmetallo-Curtius\u201d mechanism (Nature 2026, DOI: 10.1038\/s41586-026-10800-4).<\/p>\n

Most stereoselective alkyl-alkyl cross-coupling reactions proceed via a radical intermediate and use a chiral catalyst to lock in the stereochemistry of the final product, says Daniel J. Weix<\/a>, a chemistry professor at the University of Wisconsin\u2013Madison who led the development of the new reaction along with Bin Wu at Suzhou Novartis Technical Development. Although there is a recent report of an exception,<\/a> couplings that proceed via radicals tend to lose stereochemistry. \u201cYou\u2019re throwing away any chiral information that might have been in your starting material,\u201d Weix says.<\/p>\n

The new reaction builds on a nickel-catalyzed alkyl-alkyl cross-coupling reaction<\/a> that Weix\u2019s lab reported in 2024 (Science, DOI: 10.1126\/science.abi4860). The new version starts with a chiral carboxylic acid derivative that the chemists couple with an alkyl iodide. In coupling these two molecules, the reaction generates carbon monoxide.<\/p>\n

Weix says students of organic chemistry will recognize the transformation as a variation of the Curtius rearrangement. A typical Curtius rearrangement converts \u03b1-chiral carboxylic acids to \u03b1-chiral amines, with the \u03b1-carbon in an acyl nitrene migrating from carbon to nitrogen. In the new reaction, a similar migration occurs from carbon to nickel as carbon monoxide is lost to decarbonylation. The migration is a nonradical process, so the \u03b1-carbon\u2019s stereochemistry is preserved.<\/p>\n

Gregory C. Fu<\/a>, who works on enantioselective cross-couplings at the California Institute of Technology and was not involved in the work, says in an email that the reaction provides a useful new tool for synthetic chemists, \u201cgiven the availability of a wide variety of enantioenriched carboxylic acids that bear an alpha stereocenter.\u201d<\/p>\n

Weix says his team is \u201cexcited about extending both the coupling partners that we can connect with this chemistry.\u201d<\/p>\n

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