Intramolecular Pyridone/Enyne Photocycloaddition: Partitioning of the [4 + 4] and [2 + 2] Pathways

Kulyk, Svitlana; Dougherty, William G.; Kassel, W. Scott; Zdilla, Michael J.; Sieburth, Scott McN.

doi:10.1021/ol200390j

Cited by 20 publications

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“…4 The [2+2] pathway is notable for the retention of alkene geometry, suggesting a singlet photochemical pathway. Moreover, this intramolecular cycloaddition creates two quaternary carbons.…”

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“…2 During our investigations of 2-pyridone photochemistry we have studied its cycloaddition with 1,3-enynes and discovered two different pathways based on the presentation of the enyne. 3,4 When the enyne is attached through the alkyne (1), only [4+4] cyclization results and the highly strained allene product 2 is, in most cases, unstable and undergoes further reaction. In contrast, when the enyne is linked to the pyridone through the alkene (3), only [2+2] products are observed (see Scheme 1).…”

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Formation and isomerization of polycyclic 1,5-enynes

Finn

Kulyk

Sieburth

2015

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a b s t r a c t A 1,5-enyne with the alkyne flanked by a cyclopropane and a cyclobutane, formed by intramolecular [2+2] photocycloaddition of a pyridone with an enyne, undergoes gold catalyzed ring closure to give a cyclopentene, without isomerization of either small ring. The ring closure can also be effected by thiol radical conditions. The chemistry of the resulting tetracycle with its five stereogenic centers, has been studied.Ó 2015 Elsevier Ltd. All rights reserved.Assembly of polycyclic molecules with useful complexity from simple reagents is a gold standard in organic synthesis. 2 During our investigations of 2-pyridone photochemistry we have studied its cycloaddition with 1,3-enynes and discovered two different pathways based on the presentation of the enyne. 3,4 When the enyne is attached through the alkyne (1), only [4+4] cyclization results and the highly strained allene product 2 is, in most cases, unstable and undergoes further reaction. In contrast, when the enyne is linked to the pyridone through the alkene (3), only [2+2] products are observed (see Scheme 1). The stereochemically rich cyclobutane 4 presented opportunities to study the reactivity of this strained and densely functionalized structure, particularly its cis-1,5-enyne. We report herein our investigation of the formation and reactivity of 4 and related structures.The formation of [2+2] adduct 4 is notable for several reasons. In addition to creating two adjacent quaternary carbons, the cycloaddition occurs with retention of the alkene stereochemistry, whereas [2+2] cycloaddition of enones with alkenes is typically accompanied by scrambling of the alkene stereochemistry. 5 Enone photochemistry is largely triplet-derived and bond formation in enone [2+2] cycloadditions are often stepwise and reversible, leading to the stereochemical isomerization. In contrast, pyridone photochemistry is mostly singlet-derived. 6 A singlet process for the photocycloaddition of 3 would be consistent with the retention of (E) alkene geometry observed for this reaction as well as for the corresponding (Z) alkene 5, Scheme 2.In four additional examples, with hydrogen, trimethylsilyl and cyclopropyl (7a-d) terminating the alkyne, with and without bromine at C-5 of the pyridone, a clean [2+2] cycloaddition is observed, yielding the [2+2] adducts 8a-d as single isomers, Scheme 3. These reactions were typically run in NMR spectrometer tubes (3.5 mm diameter) using a 400 W medium-pressure mercury lamp in a water-cooled jacket and a Pyrex Ò filter, standardized as 0.025 M solutions of 3 or 7 in C 6 D 6 or toluene. As noted in Scheme 3 http://dx.

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Formation and isomerization of polycyclic 1,5-enynes

Finn

Kulyk

Sieburth

2015

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“…[2] Thethermal cycloadditions yield allenes embedded in six-membered rings (2)t hat isomerize to arenes (e.g. [5,6] Stability through steric shielding can be designed into strained allenes,asdescribed by Johnson and Price. Recently we reported that 1,3-enynes can be participants in [4+ +4] cycloadditions and found them to work well with pyridones (4, 7), pyrones and anthracene.…”

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“…[3,4] Thecycloadducts formed in these higher-order cycloadditions are incapable of isomerizing to arenes however, and unless an alternative pathway to relieve strain is available,t he products often undergo dimerization reactions that result in complex mixtures. [5,6] Stability through steric shielding can be designed into strained allenes,asdescribed by Johnson and Price. [7] Forthe pyridone-enyne cycloadduct 5,t he diisopropylsilyl group slows dimerization and allows isomerization of the allene to 1,3-diene 6 to occur quantitatively,largely or exclusively by an ionic mechanism.…”

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Enyne [4+4] Cycloaddition/Oxidation: Ring Contraction via Cyclopropanones and Their Anionic Ring‐Opening Reactions

2016

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Irradiation of a 1,3-enyne tethered to a 2-pyridone, in the presence of oxygen, leads to formation of a seven-membered ring product, an overall [4+4-1] reaction. This transformation involves two unstable intermediates and a sequence of unusual reactions. An initial [4+4] photocycloaddition of the enyne with the pyridone yields a 1,2,5-cyclooctatriene. Photooxidation of this triene forms a cyclopropanone and subsequent photoextrusion of carbon monoxide gives the observed 1,4-cycloheptadiene product. The first-formed cyclooctatriene and the cyclopropanone could be observed and characterized spectroscopically. The cyclopropanone underwent CO extrusion both photochemically and thermally to give the cycloheptadiene product. Addition of fluoride or acetylide to the most stable cyclopropanone occurred chemoselectively at the two different silicon groups rather than the carbonyl group. The resulting cyclopropanone ring openings gave unsaturated aldehydes.

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“…6 The intramolecular version was simpler and more interesting, Scheme 1: connecting the enyne through the alkyne (e.g., 1) gave exclusively [4 + 4]-adducts 2 whereas connecting through the alkene (4) gave only photo-[2 + 2]-products such as 5. 7 Attempts to observe the transient allenes such as 2 by IR did not bear fruit, and we therefore sought substrates that would have more intrinsic stability. Steric shielding has been used to stabilize strained allenes, 9 and so we prepared a series of more substituted photosubstrates for investigation.…”

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Stabilization, Isomerization and Rearrangement of Enyne [4 + 4]-Cycloadducts

2014

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Reactive 1,2,5-cyclooctatrienes, formed by photocycloaddition of 2-pyridones with enynes, are stabilized by steric shielding, slowing or preventing an otherwise facile [2 + 2]-dimerization reaction. Diisopropylsilyl ether-tethered reactants paired with an alkene substituent (R) produce allenes that are stable (R = TMS) or that isomerize to 1,3-dienes by hydrogen migration (R = alkyl). Under acidic conditions, hydrolysis of the photoproduct's silyl ether can lead to a [3,3]-sigmatropic rearrangement.

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Intramolecular Pyridone/Enyne Photocycloaddition: Partitioning of the [4 + 4] and [2 + 2] Pathways

Cited by 20 publications

References 23 publications

Formation and isomerization of polycyclic 1,5-enynes

Formation and isomerization of polycyclic 1,5-enynes

Enyne [4+4] Cycloaddition/Oxidation: Ring Contraction via Cyclopropanones and Their Anionic Ring‐Opening Reactions

Stabilization, Isomerization and Rearrangement of Enyne [4 + 4]-Cycloadducts

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