INVESTIGATIVE PHOTOCHEMISTRY: ELUCIDATING THE MECHANISM OF THE PHOTO-FAVORSKII REARRANGEMENT

The p-hydroxyphenacyl chromophore (pHP) is a versatile phototrigger for several biological nucleofuges, such as gamma-aminobutyric acid (GABA). The photochemistry is trenchant; irradiation discharges the nucleofuge and induces rearrangement of pHP, analogous to the ground state Favorskii rearrangement. Structure-reactivity relationships were explored with pHP GABA's. Electron donating groups lowered the release efficiency, Φdis, relative to the unsubstituted analog. Electron withdrawing carbonyl groups attenuated Φdis. Fluoro moieties modulated the pKa of pHP; protonated pHP manifested higher Φdis than their conjugate base counterparts. The reactive excited states were determined as triplets by Stern-Volmer quenching and laser flash photolysis studies. The triplet lifetimes were ~ 10-9 s with release rate constants of 107 to 108 s-1. Auxochrome substitutions lengthened the absorption wavelength of pHP but lowered Φdis. Added perchlorate salts markedly improved Φdis for pHP GABA's, imputing intermediate ion-radical pairs. Comprehensive photo-Favorskii mechanisms were posited for protonated and conjugate base forms of pHP GABA

Stereochemically Probing the photo-favorskii Rearrangement: A Mechanistic Investigation

Using model (R)-2-acetyl-2-phenyl acetate esters of (S)- or (R)-α-substituted-p-hydroxybutyrophenones (S,R)-12a and (R,R)-12b, we have shown that a highly efficient photo-Favorskii rearrangement proceeds through a series of intermediates to form racemic rearrangement products. The stereogenic methine on the photoproduct, rac-2-(p-hydroxyphenyl)propanoic acid (rac-9), is formed by closure of a phenoxy-allyloxy intermediate 17 collapsing to a cyclopropanone, the “Favorskii” intermediate 18. These results quantify the intermediacy of a racemized triplet biradical 316 on the major rearrangement pathway elusively to the intermediate 18. Thus, intersystem crossing from the triplet biradical surface to the ground state generates a planar zwitterion prior to formation of a Favorskii cyclopropanone that retains no memory of its stereochemical origin. These results parallel the mechanism of Dewar and Bordwell for the ground state formation of cyclopropanone 3 that proceed through an oxyallyl zwitterionic intermediate. The results are not consistent with the stereospecific SN2 ground state Favorskii mechanism observed by Stork, House, and Bernetti. Interconversion of the diastereomeric starting esters of (S,R)-12a and (R,R)-12b during photolysis did not occur thus ruling out leaving group return prior to rearrangement

Gas-phase Fragmentation of Deprotonated p-Hydroxyphenacyl Derivatives

Electrospray ionization of methanolic solutions of p-hydroxyphenacyl derivatives HO-C6H4-C(O)-CH2-X (X = leaving group) provides abundant signals for the deprotonated species which are assigned to the corresponding phenolate anions −O-C6H4-C(O)-CH2-X. Upon collisional activation in the gas phase, these anions inter alia undergo loss of a neutral “C8H6O2” species concomitant with formation of the corresponding anions X−. The energies required for the loss of neutral roughly correlate with the gas phase acidities of the conjugate acids (HX). Extensive theoretical studies performed for X = CF3COO in order to reveal the energetically most favorable pathway for the formation of neutral “C8H6O2” suggest three different routes of similar energy demands, involving a spirocyclopropanone, epoxide formation, and a diradical, respectively