Structural Basis for Regioisomerization in the Alkali-Metal-Mediated Zincation (AMMZn) of Trifluoromethyl Benzene by Isolation of Kinetic and Thermodynamic Intermediates

Performed with a desire to advance knowledge of the structures and mechanisms governing alkali-metal-mediated zincation, this study monitors the reaction between the TMP-dialkylzincate reagent [(TMEDA)Na(TMP)(tBu)Zn(tBu)] 1 and trifluoromethyl benzene C6H5CF3 2. A complicated mixture of products is observed at room temperature. X-ray crystallography has identified two of these products as ortho- and meta-regioisomers of heterotrianionic [(TMEDA)Na(TMP)(C6H4-CF3)Zn(tBu)], 3-ortho and 3-meta, respectively. Multinuclear NMR data of the bulk crystalline product confirm the presence of these two regioisomers as well as a third isomer, 3-para, in a respective ratio of 20:11:1, and an additional product 4, which also exhibits ortho-zincation of the aryl substrate. Repeating the reaction at 0 °C gave exclusively 4, which was crystallographically characterized as [{(TMEDA)2Na}+{Zn(C6H4-CF3)(tBu)2}−]. Mimicking the original room-temperature reaction, this kinetic product was subsequently reacted with TMP(H) to affo...