A Thermal Cascade Route to Pyrroloisoindolone and Pyrroloimidazolones

McNab, Hamish; Tyas, Richard G.

doi:10.1021/jo0712502

Cited by 26 publications

(26 citation statements)

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“…The usage of flash vacuum pyrolysis allows production of pyrrolo[1,2‐ a ]indol‐3‐ones 135 from derivative indole‐1‐ylacrylates 136 and indol‐3‐ylacrylates 137 . This method is a continuation of the works on pyrolysis of Meldrum's acid derivatives and pyrrol‐2‐ylacrylates derivatives .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Some Biological Properties of Pyrrolo[1,2‐a]indoles

Monakhova

Ryabova

Makarov

2015

Journal of Heterocyclic Chem

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Section: Introductionmentioning

confidence: 99%

Synthesis and Some Biological Properties of Pyrrolo[1,2‐a]indoles

Monakhova

Ryabova

Makarov

2015

Journal of Heterocyclic Chem

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“…The products were fully characterized by NMR spectroscopy and MS, and the data obtained were consistent with those reported in the literature ,. [11b], For adduct E ‐ 3b , an X‐ray crystallographic structure was obtained. These aliquots of purified stereoisomers were used to monitor the isomerization in acetic acid.…”

Section: Methodsmentioning

confidence: 99%

Revisiting the Intermolecular Fujiwara Hydroarylation of Alkynes

et al. 2017

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The Fujiwara hydroarylation of alkynes was reinvestigated using the addition of indole to methyl or ethyl phenylpropiolate catalyzed by Pd(OAc)2 as a model reaction. Reactions were monitored by both 1H NMR spectroscopy and electrospray ionization mass spectrometry (ESI/MS), and also through reactions carried out in the gas phase using MS/MS experiments. Contrary to the original suggestion for exclusive heteroarene activation, the data supports the coexistence of both heteroarene activation (C–H activation) and alkyne activation (Friedel–Crafts‐type pathway). Under the reaction conditions used in this work, intermediates for both mechanisms were detected by NMR spectroscopy and MS, but alkyne activation seems to be predominant according to 1H NMR spectroscopic studies and theoretical predictions. Alkyne activation is promoted by the coordination of an electrophilic palladium species to the C–C triple bond, followed by nucleophilic attack of the heteroaryl counterpart. Two previously undetected equilibria in this reaction involving the vinylpalladium intermediates and the final products were also found to be critical to the stereoselectivity of the reaction.

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“…FVP of methyl 3-(2-methylimidazol-1-yl)-3-phenylacrylate (3b; 105 mg) (conditions: T f 875 °C, T i 160 °C, P 0.010-0.060 Torr, t 15 min) gave solid yellow 3-methyl-7-phenylpyrrolo[1,2-c]imidazol-5-one (4b). 12 The entire crude pyrolysate was dissolved in a mixture of THF (2 mL) and H 2 O (10 mL), then transferred to a round-bottomed flask and heated under reflux for 6 h during which time decolorization occurred. THF and H 2 O were removed using a rotary evaporator and the product was dried under vacuum (oil pump) for 4 h to afford (Z)-5b; yield: 71 mg (72% for the two steps); mp >170°C (dec. with gas evolution).…”

Section: (Z)-3-(2-methyl-3h-imidazol-4-yl)-3-phenylacrylic Acid [(Z)-5b]mentioning

confidence: 99%

“…These heterocycles are best made by flash vacuum pyrolysis (FVP) of (imidazol-4-yl)acrylate esters 2, by an isomerization-elimination-electrocyclization sequence 10 or by FVP of 2-substituted (imidazol-1yl)acrylate esters 3, in which directed sigmatropic migration of the 1-substituent precedes the elimination and cyclization steps (Scheme 2). 11,12 Few reactions of azapyrrolizinones have been published. However, pyrrolizin-3-ones themselves are readily ringopened by treatment with hard nucleophiles 7,13 and the aza-analogues, which have an imidazole unit as a formal leaving group, would be expected to show greater reactivity.…”

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confidence: 99%

A Stereospecific Route to (Z)-Urocanic Acids

Despinoy¹,

McNab²,

Tyas³

2008

Synthesis

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Z)-Urocanic acid and its derivatives can be made stereospecifically by ring-opening of pyrrolo [1,2-c]imidazol-5-ones in aqueous tetrahydrofuran.(E)-Urocanic acid [(E)-1] is a major chemical component of the epidermis, formed from histidine by the enzyme histidase in the stratum corneum. 1 Upon ultraviolet irradiation of the skin, trans-urocanic acid [(E)-1] isomerizes to the cis-form (Z)-1, which is of current biomedical 2 and photophysical 3 interest (Scheme 1). In particular, (Z)-urocanic acid [(Z)-1] is known to have an immunosuppressive effect in vivo or in vitro and its mode of action has been recently investigated. 4Photoisomerization of the commercially available E-isomer (E)-1 5 or its methyl ester (E)-2 6 are the only known routes to Z-urocanic acid [(Z)-1]. A photostationary equilibrium between the two isomers is attained (at which the conversion reaches 70%) and so a chromatographic separation is necessary. 5,7 Relatively few derivatives of urocanic acids have been synthesized, especially as Z-isomers, though fluorinated analogues provide an interesting exception. 8In this paper, we report a new, stereospecific route to (Z)-urocanic acid [(Z)-1] and its derivatives, by ring-opening of the pyrrolo[1,2-c]imidazol-5-one (azapyrrolizinone 9-12 ) system 4. These heterocycles are best made by flash vacuum pyrolysis (FVP) of (imidazol-4-yl)acrylate esters 2, by an isomerization-elimination-electrocyclization sequence 10 or by FVP of 2-substituted (imidazol-1-yl)acrylate esters 3, in which directed sigmatropic migration of the 1-substituent precedes the elimination and cyclization steps (Scheme 2). 11,12 Few reactions of azapyrrolizinones have been published. However, pyrrolizin-3-ones themselves are readily ringopened by treatment with hard nucleophiles 7,13 and the aza-analogues, which have an imidazole unit as a formal leaving group, would be expected to show greater reactivity.In practice, heating 4a-c in aqueous THF (in the absence of any acidic or basic reagents) for three hours provided (Z)-urocanic acid [(Z)-1] and its analogues (Z)-5a,b in high yields (Scheme 3). The progress of the reaction could be monitored by the disappearance of the characteristic yellow color of the azapyrrolizinones. For the preparation of (Z)-1, it is particularly important to minimize decomposition of the azapyrrolizinone 4c by adding the THF-water mixture directly to the azapyrrolizinone in the FVP cold finger trap and carrying out the hydrolysis immediately after the pyrolysis step. Isolation and manipulation of the azapyrrolizinone 4c can cause decomposition.After the hydrolysis step, the products were isolated simply by removal of the solvents without the need for chromatography. In this way, the Z-urocanic acid [(Z)-1] and its derivatives (Z)-5a,b were obtained in 72-89% overall yields based on the pyrolysis precursor. The Z-configuration of the alkene unit of (Z)-1 and (Z)-5a was clear from their NMR spectra ( 3 J = 12.5-13.0 Hz) and in the case of (Z)-5b by a NOESY experiment. No isomerization of the alkene took place...

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A Thermal Cascade Route to Pyrroloisoindolone and Pyrroloimidazolones

Cited by 26 publications

References 30 publications

Synthesis and Some Biological Properties of Pyrrolo[1,2‐a]indoles

Synthesis and Some Biological Properties of Pyrrolo[1,2‐a]indoles

Revisiting the Intermolecular Fujiwara Hydroarylation of Alkynes

A Stereospecific Route to (Z)-Urocanic Acids

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