Diphenyl disulfide and sodium in NMP as an efficient protocol for in situ generation of thiophenolate anion: Selective deprotection of aryl alkyl ethers and alkyl/aryl esters under nonhydrolytic conditions

Aryl methyl ethers, methyl esters, aryl esters, and aryl sulfonates are chemoselectively deprotected under nonhydrolytic conditions by treatment with Ph2S2 (0.6 equiv) and Na (1.6 equiv) in NMP under reflux or at 90 degreesC. Quantitative utilization of the 'PhS' moiety as the effective nucleophilic species represents conservation of atom economy. Other solvents such as HMPA, DMPU, DMEU, and DMF afforded comparable results. Chloro, nitro, aldehyde, alpha,alpha-diketone, and alpha,beta-unsaturated ketone functionalities remain unaffected. The deprotection was found to take place in the order aryl ester > alkyl ester > aryl alkyl ether. Substrates bearing strong electron-withdrawing groups react at a faster rate than those not having such substitution. The differences in rate of reaction has been exploited for selective deprotection for intramolecular competition. An aryl acetate/benzoate is deprotected selectively in preference to a methyl ester or aryl methyl ether. Selective deprotection of a methyl ester is observed in the presence of an aryl alkyl ether.