The Photo-Favorskii Reaction of p-Hydroxyphenacyl Compounds Is Initiated by Water-Assisted, Adiabatic Extrusion of a Triplet Biradical

Abstract

p-Hydroxyphenacyl is an effective photoremovable protecting group, not least due to the fast release of its substrates, accompanied by a photo-Favorskii rearrangement of compounds 1 to p-hydroxyphenylacetic acid (2) that is transparent down to 300 nm. First used for the release of ATP from 1 (X = ATP) a decade ago, 1 the reaction has been employed in a variety of fields as diverse as neurobiology, 2 enzyme catalysis, 3 and biochemistry. 4 The nature and timing of the bond-making and bond-breaking events have not been fully elucidated despite extensive experimental and theoretical efforts by our group 5 and others. 6,7 We now report observation of the primary photoproduct, the triplet biradical 3 3, and of a new side product, p-hydroxybenzyl alcohol (6), that is formed by decarbonylation of the putative spirodione intermediate 4 at moderate water concentrations (Scheme 1). Solvent kinetic isotope effect (SKIE) studies by nanosecond laser flash photolysis (LFP) provide significant information on the role of water in the photo-Favorskii rearrangement of p-hydroxyphenacyl diethyl phosphate 1a to p-hydroxyphenylacetic acid (2). Anderson and Reese first reported the intriguing photoreaction 1(X = Cl) → 2 + HCl and suggested that the skeletal rearrangement may proceed via a spirodione intermediate 4, 8 which has yet to be detected. Intersystem crossing (ISC) of diethyl phosphate 1a is very fast, k ISC = 4 × 10 11 s −1 , 5 and we have established that the rearrangement proceeds from the triplet state, T 1. 1,4b,5 This was confirmed by Phillips et al. 7a-c Hydroxylic solvents play a major role in the rearrangement. The lifetime of T 1 decreases from several μs in degassed, dry CH 3 CN to about 0.4 ns in aqueous CH 3 CN (50% by vol). 5,7c,d The lifetime of T 1 of 1a is further reduced to 100 ± 10 ps in 87% aqueous CH 3 CN (Figure 1) and to 63 ± 10 ps in wholly aqueous solution. This was the key to revealing that the decay of T 1 left weak absorptions at 445, 420, and 330 nm, which decayed with a somewhat longer lifetime of ca. 0.6 ns. Pump-probe spectra obtained with other derivatives of 1 with good leaving groups (1b,c: X = tosylate, mesylate) also displayed the transient species possessing

Water‐ and Acid‐Mediated Excited‐State Intramolecular Proton Transfer and Decarboxylation Reactions of Ketoprofen in Water‐Rich and Acidic Aqueous Solutions

“…[34] Givens and co-workers also have suggested that a water molecule chain can carry a proton from the acidic p-OH site to the leaving-group phosphate. [35] In the case of KP, the hydrogen atom in the carboxyl group seems too far to be captured by the n-p* excited triplet-state carbonyl group by means of intramolecular hydrogen transfer. However, this process could take place through a bridge of hydrogen bonds among water molecules that connect the carbonyl and carboxyl group.…”

Fluorinated photoremovable protecting groups: the influence of fluoro substituents on the photo-Favorskii rearrangement

“…Recent studies revealed the signature absorption profile of this biradical intermediate through the appearance of three transitory bands at 320, 430, and 440 nm with a lifetime of 0.6 ns. 10 The phenoxy-oxyallyl biradical triplet intersystem crosses to the singlet biradical followed by ring closure to form the putative spirodienedione 14 originally suggested by Anderson and Reese 13 for the photo-Favorskii rearrangement.…”

“…The singlet biradical had no barrier to closure and hence was not predicted to have a significant lifetime, decaying immediately to the spirodienone. 10 The biradicals are believed to be generated through out-of-plane rotation of the acyl group with rotations that range from 8.0 ° for 1 to 41.8 ° for 8. The large twist angle for 8 is intriguing in that it may suggest a potential link between extent of fluoro substitution, particularly at the ortho positions, and the stabilization of the oxyallyl-phenoxy biradical.…”

“…This route produces a very modest yield, never more than 5%, of p-hydroxybenzyl alcohol from hydrolysis of p-quinone methide observed recently with our studies of pHP phosphates and tosylates. 10 …”

Kinon-metidi (II. dio): Fotokemijsko generiranje i razvoj primjene u fotokemoterapiji

“…Reakcija se odvija iz tripletnog pobuđenog stanja biradikalskog tipa, gdje nakon dekarbonilacije nastaje QM 74a. 54 Također je studirana reakcija fotogeneriranja QM-a 98 iz 4-hidroksiacetofenona 97 (slika 12).…”