Probing the reactivity of solid supports via Hammett relationships

A high-throughput technique for elucidating Hammett relationships on solid supports and its application to the comparison of various commercially avai lable solid supports is reported. Specifically, we report the use of compet ition experiments to derive Hammett relationships for the displacement of a solid-supported pentafluorophenyl (pfp) ester with four para-substituted a nilines (p-MeO, p-Me, p-F, p-Cl) and aniline. By taking advantage of the un ique physical properties of the solid supports, we were able to conduct com petition experiments with seven different solid supports in a single reacti on vessel. This enabled us to generate 35 Hammett plots from only 10 reacti on vessels. These studies revealed the strong dependence of the Hammett rea ction constant rho on both the solid support and solvent used in the ester displacement reaction, interestingly, the rho values obtained for reactions conducted on poly(ethylene glycol)-grafted polystyrene (PS-PEG) resin clos ely matched the corresponding solution-phase rho values, a result which sup ports the supposition that molecules attached to PS-PEG exhibit "solution-l ike" behavior. Moreover, changing the solvent from DMF to CH2Cl2 greatly re duced the support-to-support variation in rho, suggesting that the degree o f solvation or "swelling" of the solid support greatly influences the chemi cal environment around the solid-support substrate.