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).