ESIPT-Mediated Photocycloadditions of 3-Hydroxyquinolinones: Development of a Fluorescence Quenching Assay for Reaction Screening

Abstract

Irradiation of 1,2-dimethyl-3-hydroxyquinolinone (DMQ) leads to excited state intramolecular proton transfer (ESIPT) generating an 3-oxidoquinolinium species which undergoes [3+2] photocycloaddition with dipolarophiles. A parallel, fluorescence quenching assay using a microplate format has been developed to evaluate fluorescence quenching of this species with a range of dipolarophiles.We have reported excited state intramolecular proton transfer (ESIPT) 1 of 3-hydroxyflavone (3-HF) derivative 1 and photochemical [3+2] cycloaddition of the derived oxidopyrylium 2 species 2 with methyl cinnamate 3 (Figure 1). 3 The resulting cycloadduct 4 was subsequently transformed to the natural product methyl rocaglate 5. Nitrogen analogues of 3-hydroxyflavone including 1-methyl-2-methyl-3-hydroxyquinolinone (DMQ) (6) 4 have been reported to undergo ESIPT to afford 3-oxidoquinolinium 7. 5 This precedent prompted us to investigate the feasibility for photocycloaddition of oxidoquinolinium intermediates such as 7 with a variety of dipolarophiles as reaction partners.In order to study the cycloaddition reactivity of DMQ 6 under UV irradiation in the presence of various dipolarophiles, we considered a parallel screening approach. A number of recent reports have outlined use of fluorescent probes for high throughput reaction development. 6 Our initial plan was to take advantage of the inherent photochemical behavior of 6 to implement a parallel, fluorescence quenching assay. Under UV irradiation, 3-hydroxyquinolinone 6 undergoes rapid proton transfer (ns timescale) from its first excited state 6* leading to the formation of phototautomer species 7* which decays to 7 via fluorescence emission at 470 nm (Figure 2 should provide an indication of photocycloaddition reactivity. 8 In this paper, we report development of a parallel, fluorescence quenching assay using a microplate format to evaluate fluorescence quenching of this species with a range of dipolarophiles and correlation of the photophysical data with preparative photocycloadditions.We first investigated the photophysical properties of 3-hydroxyquinolinone 6. UV/Vis spectra of 6 in various solvents showed an absorbance maximum at 370 nm ( Figure 3) 8 which was well separated from absorbances of most commonly encountered dipolarophiles such that selective light absorption by the heterocycle could be easily accomplished. Upon excitation at 350 nm, dual fluorescence associated with normal excited state 6* (400 nm) and tautomeric excited state 7* (470 nm) was observed. The latter emission related to ESIPT was characterized by an unusually large Stokes shift as expected and previously reported (Figure 3). 4d The origin of this ESIPT emission was also confirmed by excitation spectra recorded at 470 nm and were found to be identical to the corresponding absorption spectra. 8 The species 7* was also observed to have a fluorescence lifetime of 16.8 ns and a very high quantum yield of 0.65 in 1,4-dioxane. 8 The latter lifetime should make 7* a trappable species in comparison...

(3+2)-Cycloaddition Reactions of Oxyallyl Cations

“…19 As shown in Scheme 6 (a), irradiation of 1,2-dimethyl-3-hydroxylquinolinone ( 33 ) could promote the generation of 3-oxidoquinolinium species 34 , which may then participate in (3+2) cycloadditions with appropriate 2π partners. While the reaction of 33 with electron-deficient 2π partners afforded only single cycloadducts 36 and 37 , respectively, electron-rich olefins such as cyclohexadiene tend to afford two regioisomers (e.g., 38 and 39 ).…”

Rapid Photoassisted Access to N,O,S‐Polyheterocycles with Benzoazocine and Hydroquinoline Cores: Intramolecular Cycloadditions of Photogenerated Azaxylylenes

“…All photoprecursors possess two characteristic emission bands in their fluorescence spectra: the 400 nm fluorescence from the initial amide form and the 540-550 nm band with a remarkably large Stokes shift, attributable to excited state intramolecular proton transfer (ESIPT) – in this particular case the emission from the S 1 state of azaxylylene. Conceivably this band can be used in a fluorescence quenching assay for high throughput screening/optimization of reaction conditions, similar to a report by Porco and Jones [8] for 3-hydroxyquinolines.…”

Rapid Photoassisted Access to N,O,S‐Polyheterocycles with Benzoazocine and Hydroquinoline Cores: Intramolecular Cycloadditions of Photogenerated Azaxylylenes

“…This second band is attributable to an excited-state intramolecular proton transfer (ESIPT), which in this particular case is due to the emission from the S 1 state of azaxylylene. Conceivably this band can be used in a fluorescence-quenching assay for high-throughput screening and optimization of the reaction conditions, an assay similar to that reported by Porco, Jones, and coworkers [8] for 3-hydroxyquinolines.…”