a photoenolization, which is mechanistically like a keto-enol tautomerization. From the enol form, the compound can finally undergo a ground-state transformation that releases the substrate. The quantum yield of this mechanism directly corresponds to the ability of the protected substrate to be a good leaving group. For good leaving groups, the rate-determining step is either hydrogen abstraction or isomerization; however, if the substrate is a poor leaving group, release is the rate-determining step. Benzyl-based PPGs Barltrop and Schofield first demonstrated the use of a benzyl-based PPG, structural variations have focused on substitution to the benzene ring, as well as extension of the aromatic core. For example, insertion of a m,m’-dimethoxy substituent was shown to increase the chemical yield ~75% due to what has been termed the “excited state meta effect.” However, this substitution is only able to release good leaving groups such as carbamates and carboxylates. Additionally, the addition of an o-hydroxy group enables the release of alcohols, phenols and carboxylic acids due to the proximity of the phenolic hydroxy to the benzylic leaving group. Finally, the carbon skeleton has been expanded to include PPGs based on naphthalene, anthracene, phenanthrene, pyrene and perylene cores, resulting in varied chemical and quantum yields, as well as irradiation wavelengths and times. Applications Use in total synthesis Despite their many advantages, the use of PPGs in total syntheses are relatively rare. Nevertheless, PPGs’ "orthogonality" to common synthetic reagents, as well as the possibility of conducting a "traceless reagent process", has proven useful in natural product synthesis. Two examples include the syntheses of ent-Fumiquinazoline and (-)-diazonamide A. The syntheses required irradiation at 254 and 300 nm, respectively. Photocaging Protecting a substrate with a PPG is commonly referred to as "photocaging." This term is especially popular in biological systems. For example, Ly et al. developed a p-iodobenzoate-based photocaged reagent, which would experience a homolytic photoclevage of the C-I bond. They found that the reaction could occur with excellent yields, and with a half-life of 2.5 minutes when a 15 W 254 nm light source was used. The resulting biomolecular radicals are necessary in many enzymatic processes. As a second example, researchers synthesized a cycloprene-modified glutamate photocaged with a 2-nitroveratrol-based PPG. As it is an excitatory amino acid neurotransmitter, the aim was to develop a bioorthagonal probe for glutamate in vivo. In a final example, Venkatesh et al. demonstrated the use of a PPG-based photocaged therapeutic. Their