The rate retarding effect of alkyl groups on arene metalation quantified

Metalation/trapping sequences applied to relatively inert, tert-alkyl substituted arenes tend to give poor yields unless the reagent is used in high concentrations. Under optimized conditions, even 1,4-bis(tert-butyl)benzene, 1,1,3,3-tetramethylindane and 1,1,2,2,3,3-hexamethylindane can be smoothly converted into derivatives. Competition experiments enable the quantitative assessment of tert-alkyl substituent effects on the metalation rates at aromatic ortho, meta and para positions. Unlike alkyl groups, hetero elements generally accelerate metalation reactions. 1,1,3,3-Tetramethyl-1,3-dihydroisobenzofuran undergoes the hydrogen/metal exchange 3–6 times faster than the indanes mentioned above, the reaction occurring at both the 5- and at the 4-position.