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 concns. 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 derivs. Competition expts. enable the quant. assessment of tert-alkyl substituent effects on the metalation rates at arom. ortho, meta and para positions. Unlike alkyl groups, hetero elements generally accelerate metalation reactions. 1,1,3,3-Tetramethyl-1,3-dihydroisobenzofuran undergoes the H/metal exchange 3-6 times faster than the indanes mentioned above, the reaction occurring at both the 5- and at the 4-position. [on SciFinder (R)]