Photoremovable protecting groups carboxylic acids

In 2003, Banerjee et al. designed an efficient photoremovable protecting group for the release of carboxylic acids based on similar p-elimination from photoenols (Scheme 14). They showed that o-alkyl acetophenone derivatives with various ester groups in the p-position release their ester moiety in high chemical yields. The authors proposed that the photorelease took place as shown in Scheme 14 but did not support the mechanism with transient spectroscopy. Formation of 21, which is expected to be the major product in the reaction, was not confirmed, and thus, the authors speculated that 21 undergoes polymerization to yield oligomers. 

Zabadal, M., Pelliccioli, A.P., Klan, P. and Wirz, J. (2001) 2,5-Dimethyl-phenacyl esters A photoremovable protecting group for carboxylic acids. Journal of Physical Chemistry A, 105, 10329-10333. 

Photoenolization [45], one of the well-documented [46] photochemical rearrangements of o-alkylphenacyl groups (Scheme 17.15) can be used for the deprotection of alcohols [47], carboxylic acids [48] and phosphates [49]. Klan chose the 2,5-dimethylphenacyl (DMP) chromophore [30] as a photoremovable protecting group, and its photolysis with >280 nm UV radiation results in an almost quantitative yield of deprotection. 

There are a number of examples of benzoin and substituted benzoin esters that have been employed as photoremovable protecting groups for carboxylic acids. Among these, the application of benzoin as a traceless linker for solid-phase synthesis of oligopeptides and introduction of Fmoc-protected amino acids by Balasubramanian ° is instructive. As an example, the release of Fmoc-Ala shown in Eq. 69.21 occurs upon photolysis at 350. Balasubramanian found that the maximum yield was obtained after a 2-h photolysis as determined by HPLC (Eq. (69.21). 

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