NMR kinetic studies on the decomposition of beta-amidozinc reagents: optimization of palladium-catalyzed cross-coupling with acid chlorides.
The decomposition of beta-amidozinc reagent 4 by beta-elimination has been shown to be a unimolecular process in both THF and DMF as solvent, with relative rates of 4:1 at room temperature, and activation parameters have been determined. These results indicate the beta-elimination is a syn-process. NMR experiments reveal that as little as 2 equiv of DMF can have a significant stabilizing influence on reagent 4. Use of a mixture of DMA and toluene as the bulk solvent, in place of DMF, has allowed successful palladium-catalyzed cross-coupling reactions of both 4 and the homologous reagent 5 with acid chlorides to yield unsymmetrical ketones (nine examples).
Dexter
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Merck Sharp and Dohme Research Laboratories, Neuroscience Research Park, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR, UK.
Hunter
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Jackson
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Elliott
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D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry*; D002384:Catalysis; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D010165:Palladium / Q000737:chemistry*
D000577:Amides; D000596:Amino Acids; D007202:Indicators and Reagents; C416963:amidozinc; D010165:Palladium