The Power of Solvent in Altering the Course of Photorearrangements

Abstract

A clean bifurcation between two important photochemical reactions through competition of a triplet state Type II H-abstraction reaction with a photo-Favorskii rearrangement for (o/p)-hydroxy-o-methylphenacyl esters that depends on the water content of the solvent has been established. The switch from the anhydrous Type II pathway that yields indanones to the aqueousdependent pathway producing benzofuranones occurs abruptly at low water concentrations (~8%). The surprisingly clean yields suggest that such reactions are synthetically promising.An intramolecular Type II reaction of alkylphenones, especially 2-methylacetophenoes, produces high yields of photoenols that have been shown to be valuable reactive intermediates. 1 When a leaving group (X) is present in the α-position of 2-alkylacetophenones (1), longer-lived (E)-photoenols liberate HX to give indanones 2 (2 ; Scheme 1) that can be employed as precursors to elaborate products used in synthetic methodology. 3 Likewise, the photo-Favorskii rearrangement of α-substituted phydroxyacetophenones (3) to p-hydroxyphenylacetic acid (4), discovered more recently, has enjoyed success in a variety of applications because of its rapid release of nucleofuges (Scheme 1). 4 Both reactions have exhibited very good photochemical efficiencies and are relatively free of side reactions that produce complicated product mixtures. The similarity of the chromophores, the common triplet state origin for reaction, and the extensive understanding of the mechanistic photochemistry 5 have prompted us to explore the intersection of the photochemical pathways to uncover which parameters control the pathway followed by a chromophore common to both. It is a rare occurrence in organic photochemistry when one can completely and cleanly divert the reaction or rearrangement pathway from a single product type to an alternative * parkbs@dongguk.edu; givensr@ku.edu; klan@sci.muni.cz. Supporting Information Available:Experimental details and characterization data for products are provided. This material is available free of charge via the Internet at http://pubs.acs.org. 3a Since it is well known that electron donating hydroxy and methoxy groups suppress Type II reactivity 6 and nearly as well known that the photo-Favorskii rearrangement has a strong affinity for water, 4k,7 we assumed that these two reaction pathways might be separated by the water content of the solvent media. In this work, the analogs of 4-hydroxyphenacyl derivatives with good leaving groups necessary for the photo-Favorskii process were fitted with 2-methyl substituent for efficient Type II hydrogen abstraction reaction to compete with the photo-Favorskii rearrangement. As an extension, a similar design, in which the 2-hydroxyphenacyl derivatives were fitted with a 6-methyl group, was also examined. NIH Public Access Synthesis of Phenacyl Esters4-Hydroxy-2-methyl (9a-c) and 2-hydroxy-4,6-dimethylphenacyl (14) esters, and the corresponding benzyl (10) and methyl (13) ethers were prepared by α-bromination of acetophen...

2-Hydroxyphenacyl ester: a new photoremovable protecting group

“…This photoreaction was suppressed when dry solvents were used, which is also known from the photochemistry of 1 . 9,22 However, water obviously does not trap any reactive intermediates, which was demonstrated for 3a by isotopic labeling experiments (Scheme 6 and the related text in the Results).…”

“…9 This phototransformation, which led to the concomitant release of a carboxylic acid, appears to parallel the photo-Favorskii pathway of the pHP chromophore. In contrast to the photorearrangement of 1 , the decarbonylation product (benzyl alcohol) was not formed by the photolysis of 3 .…”

“…9 It was suggested that the products are formed via the photo-Favorskii-type rearrangement through a putative spirodienedione intermediate.…”

A Photo-Favorskii Ring Contraction Reaction: The Effect of Ring Size

“…Bromination of 9a–c ( n = 1–3) 47 and subsequent silver-promoted sulfoxydebromination 23 of 12 gave rise to the mesylates 8a–c ( n = 1–3; Scheme 2); see also the Supporting Information for the synthesis of 9c,d (Scheme S1, Supporting Information).…”

“…23 Unlike its namesake, the classic ground-state Favorskii rearrangement that has received extensive investigation, 24–30 the range of possibilities and the theoretical treatments of the photo-Favorskii rearrangement 14 have not been adequately addressed. The current understanding of the photo-Favorskii mechanism also continues to be the subject of considerable debate.…”