Stereochemically Probing the Photo-Favorskii Rearrangement: A Mechanistic Investigation

Abstract

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.

Photoremovable Protecting Groups in Chemistry and Biology: Reaction Mechanisms and Efficacy

“…104 The rearrangement proceeds from the chromophore’s triplet excited state ( 3 24 ) by a concerted departure of the leaving group and the phenolic proton generating the triplet biradical 3 28 . Intersystem crossing of 3 28 gives an intermediate common to the ground state Favorskii rearrangement, 102a−102c the putative cyclopropanone, 86,98,102 that either hydrolyzes or decarbonylates on its pathway to the final products.…”

2-Diazo-1-(4-hydroxyphenyl)ethanone: a versatile photochemical and synthetic reagent

“…The solvent was evaporated, and the yellow residue was purified by flash chromatography with a gradient solvent system. [EtOAc-hexane (1 : 4), EtOAc-hexane (1 : 3), and EtOAchexane (1 : 2)] to afford 4-(2-diazoacetyl)-2-methoxyphenyl acetate (7b) as a yellow crystalline solid (645 mg, 69% yield): mp = 96-99 °C; 1 H NMR (500 MHz, CD 3 COCD 3 ) δ ppm 7.56 (1H, d, J = 2 Hz), 7.47-7.45 (1H, d, J = 8.2 Hz), 7.18-7.16 (1H, d, J = 8.2 Hz), 6.63 (1H, s), 3.90 (3H, s), 2.26 (3H, s); 13 2-Diazo-1-(4-hydroxyphenyl)ethan-1-one, 1a (α-diazo-phydroxyacetophenone). The general method of Das et al 64 was followed with modifications.…”

“…2,11 Based on literature precedence, the pWR and pFR rearrangements follow two completely different pathways, yet arrive at one common major product, carboxylic acid 4. One common feature of both the pWR 12 and pFR 1-3, 13 for aryl ketones is that they commence by heterolytic departure of a leaving group from an excited state of the α-substituted phenacyl ketone (e.g., 1) followed by 1,2-aryl migration. For the pFR, a required p-hydroxyphenacyl group assists the leaving group heterolysis in aqueous solvents through concomitant loss of the phenolic proton, whereas the pWR should not be limited by nor require any special assistance from the aryl substituent.…”

Supramolecular Storage and Controlled Photorelease of an Oxidizing Agent using a Bambusuril Macrocycle

“…In addition to typical photo‐Favorskii rearrangement products, 4‐hydroxyphenylacetic acid derivatives ( p Ac , 50 and 38 % yields for p HP1 and p HP2 , respectively), and 4‐hydroxybenzyl alcohol derivatives ( Bn‐OH , 12 and 17 % yields, respectively) that often accompany this rearrangement, photosolvolysis (hydrolysis) products, 4‐hydroxyphenacyl alcohols, were produced in 36 and 30 % yields, respectively ( p HP‐OH ; Scheme , Table S2, Figures S3 and S4). Photosolvolysis has also been reported in the case of simple phenacyl derivatives as well as of 4‐hydroxyphenacyl derivatives, although in very low chemical yields . Furthermore, the photochemical behavior of p HP1 after excitation was studied by picosecond pump‐and‐probe and nanosecond transient spectroscopies (see the Supporting Information).…”

“…Photosolvolysis has also been reported in the case of simple phenacyl derivatives [33] as well as of 4-hydroxyphenacyl derivatives, although in very low chemicaly ields. [34] Furthermore, the photochemical behavior of pHP1 after excitation was studied by picosecond pump-and-probe and nanosecond transient spectroscopies (see the Supporting Information). The mixture of tautomeric triplet state forms of pHP1 was detected possessing an average lifetimeo fa round 30 ns (the individual triplet-state forms could not be separated under experimental conditions), which is analogous to photobehavior of 4-hydroxyacetophenone.…”