The p-Hydroxyphenacyl Photoremovable Protecting Group

This review is intended to provide the reader who is interested in the historical development of the recent research on photoremovable protecting groups, phototriggers, and “caged” compounds and to provide some insight into the genesis of our entry into the field through our most recent discoveries. Several other investigations have paralleled our development of a photoremovable protecting group and these can be found in one of the growing number of important recent reviews on the subject [2]. In keeping with our main theme, the scope of this review will be limited to the chemistry and applications of phototriggers derived from derivatives of p-hydroxyacetophenone. Two additional caveats are necessary. The initial suggestion that derivatives of this chromophore could be employed as photoremovable protecting groups came from earlier work by Sheehan and his coworkers [3,4]. Another significant contribution came from Anderson and Reese [5] who were the first to show that p-methoxy and p-hydroxy derivatives of phenacyl chloride rearranged, in part, to the corresponding methyl phenylacetates (Eq. 1). None of these early workers chose to exploit the advantages or the range of possibilities that this chromophore afforded as a photoremovable protecting group. We have done so [6]. Recently, other research groups [7] have recognized the potential of these two chromophores and have contributed to the development of the field. These most recent studies will be included where appropriate. A brief history of the development of this class of photoremovable protecting groups begins with a discussion of Sheehan and Wilson’s benzoin studies [3,4]. The report on these studies will be followed by a review of the current state of understanding of the mechanisms for the photorelease step, and the review will conclude with a limited number of relevant applications that have been exploited for the p-hydroxyphenacyl class of phototriggers.