O-quinone methides. II. Trapping with production of chromans

Bolon, Donald A.

doi:10.1021/jo00836a016

Cited by 62 publications

(23 citation statements)

References 5 publications

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“…QMs are too reactive to be stored, so they have to be generated in situ. Methods to prepare QMs in thermal reactions rely on the oxidation of phenols, dehydration from hydroxybenzyl alcohols, elimination of nitriles from 1,2‐benzoxazines, and fluoride‐induced desilylation . Photochemical methods are more interesting, particularly in biological systems, as they enable access to QMs under much milder conditions.…”

Section: Introductionmentioning

confidence: 99%

“…[34][35][36] QMs are too reactive to be stored, so they have to be generated in situ. Methods to prepare QMs in thermal reactions rely on the oxidation of phenols, [37] dehydrationfrom hydroxybenzyl alcohols, [38,39] elimination of nitriles from 1,2-benzoxazines, [40] and fluoride-induced desilylation. [22,41] Photochemical methodsa re more interesting, particularly in biological systems,a st hey enablea ccess to QMs under much milder conditions.P hotochemical methods to generate QMs include the photoelimination of HF [42] or acetic acid, [43] photodeamination from the Mannich salts of the corresponding phenols, [19,44] phototautomerization of suitably substituted phenols [45,46] or naphthols, [47] and photohydration of alkenes.…”

Section: Introductionmentioning

confidence: 99%

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Ultrafast Adiabatic Photodehydration of 2‐Hydroxymethylphenol and the Formation of Quinone Methide

Škalamera

Antol

Mlinarić‐Majerski

et al. 2018

Chemistry A European J

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The photochemical reactivity of 2-hydroxymethylphenol (1) was investigated experimentally by photochemistry under cryogenic conditions, by detecting reactive intermediates by IR spectroscopy, and by using nanosecond and femtosecond transient absorption spectroscopic methods in solution at room temperature. In addition, theoretical studies were performed to facilitate the interpretation of the experimental results and also to simulate the reaction pathway to obtain a better understanding of the reaction mechanism. The main finding of this work is that photodehydration of 1 takes place in an ultrafast adiabatic photochemical reaction without any clear intermediate, delivering quinone methide (QM) in the excited state. Upon photoexcitation to a higher vibrational level of the singlet excited state, 1 undergoes vibrational relaxation leading to two photochemical pathways, one by which synchronous elimination of H O gives QM 2 in its S state and the other by which homolytic cleavage of the phenolic O-H bond produces a phenoxyl radical (S ). Both are ultrafast processes that occur within a picosecond. The excited state of QM 2 (S ) probably deactivates to S through a conical intersection to give QM 2 (S ), which subsequently delivers benzoxete 4. Elucidation of the reaction mechanisms for the photodehydration of phenols by which QMs are formed is important to tune the reactivity of QMs with DNA and proteins for the potential application of QMs in medicine as therapeutic agents.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ultrafast Adiabatic Photodehydration of 2‐Hydroxymethylphenol and the Formation of Quinone Methide

Škalamera

Antol

Mlinarić‐Majerski

et al. 2018

Chemistry A European J

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“…22 Thus, we have recently shown that the antiproliferative activity of QMs formed in the phototautomerization of hydroxyphenylanthracenes is due to the reaction with intracellular proteins, rather than with DNA. 23 Formation of QMs often requires harsh conditions such as elevated temperature, 24,25 or the use of biologically inacceptable oxidants 26 or F − . 13 On the contrary, photochemical reactions require mild conditions which allow for the generation of QMs in living cells.…”

Section: Introductionmentioning

confidence: 99%

Photochemical formation of quinone methides from peptides containing modified tyrosine

et al. 2016

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We have demonstrated that quinone methide (QM) precursors can be introduced in the peptide structure and used as photoswitchable units for peptide modifications. QM precursor 1 was prepared from protected tyrosine in the Mannich reaction, and further used as a building block in peptide synthesis. Moreover, peptides containing tyrosine can be transformed into a photoactivable QM precursor by the Mannich reaction which can afford monosubstituted derivatives 2 or bis-substituted derivatives 3. Photochemical reactivity of modified tyrosine 1 and dipeptides 2 and 3 was studied by preparative irradiation in CHOH where photodeamination and photomethanolysis occur. QM precursors incorporated in peptides undergo photomethanolysis with quantum efficiency Φ = 0.1-0.2, wherein the peptide backbone does not affect their photochemical reactivity. QMs formed from dipeptides were detected by laser flash photolysis (λ ≈ 400 nm, τ = 100 μs-20 ms) and their reactivity with nucleophiles was studied. Consequently, QM precursors derived from tyrosine can be a part of the peptide backbone which can be transformed into QMs upon electronic excitation, leading to the reactions of peptides with different reagents. This proof of principle showing the ability to photochemically trigger peptide modifications and interactions with other molecules can have numerous applications in organic synthesis, materials science, biology and medicine.

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“…A variety of methods of ortho-quinone methide generation have been reported (2), including pyrolysis of ortho-(methoxyaky1)-or ortho-(hydroxyaky1)phenols (3, 6-8, 12, 13), dehydrohalogenation of 2-chloromethylphenol (4,20), one-electron oxidation of ortho-substituted phenols (5,9), desilylation of disilylated ortho-hydroxybenzyl alcohol (15), photochemical decarbonylation of benzofuran-2(3H)-one (10) and treatment of ortho-(1-(alkylthio)alkyl)phenols with a variety of metal oxides under mild conditions (1 1, 16, 17). Recently we reported the preparation of a variety of orthoalkyl, ortho-akoxakyl, and ortho-thioakyl phenols from 2-phenyl-4H-1,3,2-benzodioxaborins, presumably via the quinone methide intermediate (21).…”

Section: Introductionmentioning

confidence: 99%

Reactions of 2-phenyl-4H-1,3,2-benzodioxaborin, a stable ortho-quinone methide precursor

Chambers¹,

Crawford²,

Williams³

et al. 1992

Can. J. Chem.

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Thermolysis of 1-phenyl-4H-1,3,2-benzodioxaborins generated the corresponding ortho-quinone methides, which were found to undergo intermolecular cycloaddition reactions with ethyl vinyl ether, dihydropyran, p-methylstyrene, cyclohexene, and 1-ethoxy-1-z-trimethylsiloxy-1-propenes to give various substituted chromans. Intramolecular trapping of the quinone methides with an olefin led to the syntheses of several analogs of tetrahydrocannabinols. ortho-Quinone methides, generated by treatment of the 2-phenyl-4H-1,3,2-benzodioxaborins with a Lewis acid, react with various nucleophiles to give the corresponding 1,4-addition products. Thus, alkyl and aryl thiols, alcohols, amine, hydride, ally1 trimethylsilane, acetophenone, and diethylmalonate as well as some aryl compounds react with the quinone methide to give various 2-substituted phenols. Intramolecular reaction of the quinone methide with an aryl group led to the preparation of some 4-phenylchromans and tetralins. La thermolyse des 2-phknyl-4H-1,3,2-benzodioxaborines conduit aux ortho-quinomkthanes correspondantes qui subissent des rkactions de cycloaddition interrnolkculaires avec l'ethoxykthkne, le dihydropyrane, le p-mkthylstyrkne, le cyclohexkne et les 1 -6thoxy-1 -z-trimkthylsiloxyprop-1 -knes pour conduire a divers chromanes substituks. Le pikgeage intrarnolkculaire des quinomkthanes avec une olefine permet la synthkse de plusieurs analogues des tktrahydrocannabinols. Les ortho-quinomkthanes, prCparCs par traitement des 2-phknyl-4H-1,3,2-benzodioxaborines avec un acide de Lewis, rkagissent avec divers nuclkophiles pour donner les produits d'additions-1,4 correspondants. Ainsi, les alkyl-et aryl-thiols, les alcools, les amines, les hydrures, l'allyltrim~thylsilane, I'acCtophknone et le malonate d'kthyle ainsi que certains composks aromatiques rkagissent avec le quinomkthane pour conduire a divers phknols substituks en position 2. La reaction intramolCculaire des quinomkthanes avec un groupe aryle conduit a la prkparation de quelques 4-phknylchromanes et de tktralines.[Traduit par la rkdaction]

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O-quinone methides. II. Trapping with production of chromans

Cited by 62 publications

References 5 publications

Ultrafast Adiabatic Photodehydration of 2‐Hydroxymethylphenol and the Formation of Quinone Methide

Ultrafast Adiabatic Photodehydration of 2‐Hydroxymethylphenol and the Formation of Quinone Methide

Photochemical formation of quinone methides from peptides containing modified tyrosine

Reactions of 2-phenyl-4H-1,3,2-benzodioxaborin, a stable ortho-quinone methide precursor

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