The new concept of alkali-metal-mediated zincation (AMMZ), formally a zinc−hydrogen exchange reaction but one that requires the participation of an alkali metal, is applied here to the alkyl aryl ether anisole, an important molecule for studying directed ortho-metalation (DoM) chemistry. Treating one molar equivalent of anisole with the lithium dialkyl-TMP zincate reagent [THF·Li(μ-TMP)(μ-tBu)Zn(tBu)] (1) in hexane solution affords the mono-ortho-zincated complex [THF·Li(μ-TMP)(μ-o-C6H4OMe)Zn(tBu)] (2), which establishes that 1 functions as an alkyl base although previously it was regarded as an amido (TMP) base in other DoM applications. Treating two molar equivalents of anisole with 1, and increasing the reaction time, affords the bis-ortho-zincated complex [THF·Li(μ-TMP)(μ-o-C6H4OMe)Zn(o-C6H4OMe)] (3), which establishes that 1 can also function as a dual alkyl base. Omitting THF and rerunning the reaction with one or two molar equivalents of anisole affords [Ph(Me)O·Li(μ-TMP)(μ-o-C6H4OMe)Zn(tBu)] (4), which remarkably contains a combination of neutral and ortho-deprotonated anisole ligands. On isolating crystalline 4 from solution and adding THF, it converts to 2 and then to 3 on further stirring of the solution, as determined by NMR studies. This fact, along with other observations, would suggest that a complex-induced proximity effect does not need to be invoked to explain the observed zincation of anisole. The crystal structures of 2−4 are presented, as are their 1H, 13C, and 7Li NMR spectra recorded in C6D6 solution.
- directed ortho-metalation
- tertiary aromatic amides
Clegg, W., Dale, S. H., Drummond, A. M., Hevia, E., Honeyman, G. W., & Mulvey, R. E. (2006). Alkali-metal-mediated zincation of anisole: synthesis and structures of three instructive ortho-zincated complexes. Journal of the American Chemical Society, 128(23), 7434-7435. https://doi.org/10.1021/ja061898g