Demand-Based Thiolate Anion Generation under Virtually Neutral Conditions: Influence of Steric and Electronic Factors on Chemo- and Regioselective Cleavage of Aryl Alkyl Ethers

Thiolate anions have been generated in a "demand-based" fashion under virtually neutral conditions for chemoselective deprotection of aryl alkyl ethers. Solvents play the critical role in making the reaction effective and should have high values of epsilon (>30), molecular polarizabilities (>10), and DN (>27) and low values of AN (<14). However, it is the combined effect of all of these physical properties that make a particular solvent effective. The reaction rates of cleavage of various aryl alkyl ethers are dependent on the steric crowding around the O-alkyl carbon and follow the order propargyl approximately allyl approximately benzyl > methyl > ethyl. Electron-withdrawing substituents increase the rate of ether cleavage reaction. The influence of the steric and electronic factors have been successfully exploited for selective deprotection of aryl alkyl ethers during inter- and intramolecular competitions.