Cyanocuprates Boost Ketone Synthesis | Chemical & Engineering News
Volume 89 Issue 39 | p. 27 | Concentrates
Issue Date: September 26, 2011

Cyanocuprates Boost Ketone Synthesis

Approach improves direct conversion of carboxylic acids to ketones relative to organolithium reagents
Department: Science & Technology
Keywords: organometallics, ketone, carboxylic acid, organic synthesis, copper

By pairing copper and lithium together in a single reagent, Douglas T. Genna and Gary H. Posner at Johns Hopkins University have created an improved method for the direct conversion of carboxylic acids into ketones (Org. Lett., DOI: 10.1021/ol202237j). This fundamental organic reaction is often carried out indirectly by first transforming the acid into an acyl chloride or an amide and then using a copper, lithium, or magnesium reagent to form the ketone. Genna and Posner found that dialkylcuprates, R2CuLi•LiCN, formed in situ from an alkyllithium and cuprous cyanide, produce ketones directly and avoid formation of a tertiary alcohol side product that is a problem when using alkyllithium reagents alone. In addition, when using substrates with a chiral carbon adjacent to the carboxylic acid, the new treatment retains stereochemical purity better than solo alkyllithium reagents. In one example the chemists added (S)-2-phenylbutyric acid to an excess of (CH3)2CuLi•LiCN, producing gram amounts of the methyl ketone in 93% yield and 98% enantiomeric excess (ee). Attempting the same reaction with CH3Li alone yielded 66% ketone and 92% ee. The researchers believe the heightened stability of a dicopper-ketal intermediate relative to a dilithium intermediate leads to the success of the approach.

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