Evaluation of 2-(piperidine-1-yl)-ethyl (PIP) as a protecting group for phenols: Stability to ortho-lithiation conditions and boiling concentrated hydrobromic acid, orthogonality with most common protecting group classes, and deprotection via Cope elimination or by mild Lewis acids

Abstract

A new protecting group, 2-(piperidine-1-yl)-ethyl (PIP), was evaluated as a protecting group for phenols. The PIP group was stable to ortho -lithiation conditions and refluxing with concentrated hydrobromic acid. Deprotection was accomplished by two routes, oxidation to N -oxides followed by Cope elimination (CE) and subsequent hydrolysis or ozonolysis of the vinyl ether or one-step deprotection by BBr 3 •Me 2 S. The PIP group is orthogonal to the O -benzyl, O -acetyl, O-t -butyldiphenylsilyl, O -methyl, O-p -methoxybenzyl, O -allyl, O -tetrahydropyranyl and N-t -butoxy carbonyl groups. The CE step was systematically studied and was found to give higher yields when the reaction was performed in the presence of silylating agents.