Photocleavable Linkers for Carboxylic Acids

The development of light-sensitive protective groups began in the early 1960s [129-131] and led to the identification of several functionalities that could be selectively cleaved under UV irradiation (for a review, see [132]). Some of these protective groups, such as 2-nitrobenzyl esters, carbonates, or carbamates [131,133-135], benzoin [136-139], and other phenacyl esters [140] were also found to be useful as photocleavable linkers. 

In 1998, a new type of light-sensitive linker based on the photolysis of tert-butyl ketones was developed by Peukert and Giese (Entry 7, Table 3.6). The proposed 

Loaded resin Cleavage conditions Product, yield (purity) Ref. 

This linker proved to be stable under a variety of reaction conditions (e.g. 50% TFA or 5% BF3OEt2 in DCM, 20 °C, 2 h 5% DBU in toluene, 80 °C, 2 h). An additional advantage of this linker, as compared with 2-nitrobenzyl alcohol derivatives, is that no UV-absorbing products are formed during photolysis. This enables fast and complete photolytic detachment of the resin-bound product. Relatively short wavelengths ( 340 nm) are, however, required to effect cleavage. 

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Most photocleavable linkers for carboxylic acids used today are based on the photoisomerization of 2-nitrobenzyl esters and on the light-induced cleavage of phen-acyl esters (Figure 3.10). Several possible mechanisms have been proposed for the photolytic cleavage of benzoin esters. One of the most recent is the dissociation of the excited phenacyl ester into a carboxylate and a phenacyl cation ( photosolvolysis , Figure 3.10 [136]). 

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