Clarification of the Stereochemical Course of Nucleophilic Substitution of Arylsulfonate-Based Nucleophile Assisting Leaving Groups

Abstract

Secondary alcohols modified as tosylates, PEG-sulfonates, or quisylates undergo inversion of configuration at the reacting center when treated with lithium halide in acetone at reflux, where the PEG-sulfonates and quisylates are substantially more reactive. In sterically hindered cases, elimination is a competing process. In contrast, when treated with TiCl(4), simple secondary sulfonates give chloride products with partial inversion of configuration. Any observed retention of configuration in a given alkyl sulfonate substrate under these conditions is likely due to neighboring group participation or diastereoselective attack on a carbocation (or ion pair) rather than an S(N)i mechanism.