Weinreb ketone synthesis

The Weinreb ketone synthesis is a chemical reaction used to transform N,O-dimethylhydroxamic acids (Weinreb amides, 1) into ketones (3).^[1]

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Addition of the organometallic nucleophile to the Weinreb amide produces a stable tetrahedral chelate (2), which upon hydrolysis produces the desired ketone.

Applicable organometallic nucleophiles include organolithium reagents, Grignard reagents, and phosphonium ylides^[2].

Weinreb amides are synthesized typically from their corresponding carboxylic acids.^[3][4][5][6]

Variations

Reaction of Weinreb amides with lithium aluminium hydride will form aldehydes.^[7]

References

1. ^  Nahm, S.; Weinreb, S.M. Tetrahedron Lett. 1981, 22, 3815-3818.
2. ^  Murphy, J. A.; Commeureuc, A. G. J.; Snaddon, T. N.; McGuire, T. M.; Khan, T. A.; Hisler, K.; Dewis, M. L.; Carling, R. Org. Lett. 2005, 7, 1427-1429.
3. ^  Fehrentz, J.-A.; Castro, B. Synthesis 1983, 676.
4. ^  De Luca, L.; Giacomelli, G.; Taddei, M. J. Org. Chem. 2001, 66, 2535-2537.
5. ^  Woo, J. C. S.; Fenster, E.; Dake, G. R. J. Org. Chem. 2004, 69, 8984-8986.
6. ^  Tunoori, A. R.; White, J. M.; Georg, G. I. Org. Lett. 2000, 2, 4091-4093. (Article, PDF)
7. ^  Goel, O. P.; Krolls, U.; Stier, M.; Kesten, S. Organic Syntheses, Coll. Vol. 8, p.68 (1993); Vol. 67, p.69 (1989). (Article)

See also

• Reformatsky reaction