Abstract
Three cinnamyl ether spacers (non-methyl, alpha-methyl, and gamma-methyl) for caging of phenols have been synthesized and are physiologically stable. When triggered, the gamma-methyl spacer releases phenols (pK(a) 7.8 and 9.8) with a t(1/2) < 30 s and <2 min in aqueous and aqueous-organic solvent, respectively. The alpha-methyl spacer releases a phenol (pKa 7.8) with a t(1/2) = 27 and 54 min. For the gamma-methyl spacer, the results suggest the presence of a resonance and inductively stabilized aza-cinnamyl methide.