SmI<sub>2</sub>–H<sub>2</sub>O-mediated 5-exo/6-exo lactone radical cyclisation cascades

Yalavac, Irem; Lyons, Sarah E.; Webb, Michael R.; Procter, David J.

doi:10.1039/c4cc05404k

Cited by 15 publications

(3 citation statements)

References 43 publications

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“…After the solvent had evaporated, (5-iodopent-1-yn-1-yl)benzene was isolated (1.474 g, 91%) as a brown liquid, which matched previously reported spectra. Without any further purification, we proceeded to the next step: 52 1 H NMR (400 MHz, CDCl 3 ) δ 7.41 (ddd, J = 6.2, 4.5, 2.7 Hz, 2H), 7.34−7.09 (m, 3H), 3.37 (t, J = 6.8 Hz, 2H), 2.56 (t, J = 6.7 Hz, 2H), 1.22 (t, J = 7.0 Hz, 2H).…”

Section: The Of Organic Chemistrymentioning

confidence: 99%

Fenton-Inspired C–H Functionalization: Peroxide-Directed C–H Thioetherification

2019

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Substoichiometric iron mediates the thioetherification of unactivated aliphatic C−H bonds directed by resident silylperoxides. Upon exposure to a catalytic amount of iron(II) triflate, TIPS-protected peroxides bearing primary, secondary, and tertiary C−H sites undergo chemoselective thioetherification of remote C−H bonds with diaryl disulfides. The reaction demonstrates a broad substrate scope and functional group tolerance without the use of any noble metal additives. Mechanistic experiments suggest that the reaction proceeds through 1,5-H atom abstraction by a hydroxyl radical generated with iron.

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Section: The Of Organic Chemistrymentioning

confidence: 99%

Fenton-Inspired C–H Functionalization: Peroxide-Directed C–H Thioetherification

2019

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“…For example, homologation of the tether at the α position grants access to [5.4.0]bicyclic tertiary alcohol products 63, albeit in lower yield because of the challenging nature of the 6-exo-trig cyclization that terminates the cascade sequence (Scheme 27A). 62…”

Section: Cascade Processes Utilizing Follow-up Cyclizationsmentioning

confidence: 99%

“…Preliminary studies showed the feasibility of re-engineering the cascade cyclizations to deliver a range of molecular architectures. For example, homologation of the tether at the α position grants access to [5.4.0]bicyclic tertiary alcohol products 63 , albeit in lower yield because of the challenging nature of the 6-exo-trig cyclization that terminates the cascade sequence (Scheme A) . Furthermore, allenyllactones 64 undergo “right then right” cascade cyclizations upon treatment with SmI 2 –H 2 O to deliver bridged bicyclic tertiary alcohol products 65 in moderate yields (Scheme B) …”

Section: Exploiting Radical Anions Derived From Carboxylic Acids In C...mentioning

confidence: 99%

Sm(II)-Mediated Electron Transfer to Carboxylic Acid Derivatives: Development of Complexity-Generating Cascades

2015

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Reductive electron transfer (ET) to organic compounds is a powerful method for the activation of substrates via the formation of radicals, radical anions, anions, and dianions that can be exploited in bond-cleaving and bond-forming processes. Since its introduction to the synthetic community in 1977 by Kagan, SmI2 has become one of the most important reducing agents available in the laboratory. Despite its widespread application in aldehyde and ketone reduction, it was widely accepted that carboxylic acid derivatives could not be reduced by SmI2; only recently has our work led to this dogma being overturned, and the reduction of carboxylic acid derivatives using SmI2 can now take its place alongside aldehyde/ketone reduction as a powerful activation mode for synthesis. In this Account, we set out our studies of the reduction of carboxylic acid derivatives using SmI2, SmI2-H2O, and SmI2-H2O-NR3 and the exploitation of the unusual radical anions that are now accessible in unprecedented carbon-carbon bond-forming processes. The Account begins with our serendipitous discovery that SmI2 mixed with H2O is able to reduce six-membered lactones to diols, a transformation previously thought to be impossible. After the successful development of selective monoreductions of Meldrum's acid and barbituric acid heterocyclic feedstocks, we then identified the SmI2-H2O-NR3 reagent system for the efficient reduction of a range of acyclic carboxylic acid derivatives that typically present a significant challenge for ET reductants. Mechanistic studies have led us to propose a common mechanism for the reduction of carboxylic acid derivatives using Sm(II), with only subtle changes observed as the carboxylic acid derivative and Sm(II) reagent system are varied. At the center of our postulated mechanism is the proposed reversibility of the first ET to the carbonyl of carboxylic acid derivatives, and this led us to devise several strategies that allow the radical anion intermediates to be exploited productively in efficient new processes. First, we have used internal directing groups in substrates to "switch on" productive ET to esters and amides and have exploited such an approach in tag-removal cyclization processes that deliver molecular scaffolds of significance in biology and materials science. Second, we have exploited external ligands to facilitate ET to carboxylic acid derivatives and have applied the strategy in telescoped reaction sequences. Finally, we have employed follow-up cyclizations with alkenes, alkynes, and allenes to intercept radical anion intermediates formed along the reaction path and have employed this strategy in complexity-generating cascade approaches to biologically significant molecular architectures. From our studies, it is now clear that Sm(II)-mediated ET to carboxylic acid derivatives constitutes a general strategy for inverting the polarity of the carbonyl, allowing nucleophilic carbon-centered radicals to be formed and exploited in novel chemical processes.

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Selective Synthesis of Cyclooctanoids by Radical Cyclization of Seven‐Membered Lactones: Neutron Diffraction Study of the Stereoselective Deuteration of a Chiral Organosamarium Intermediate

et al. 2016

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Seven-membered lactones undergo selective SmI 2 -H 2 O-promoted radical cyclization to form substituted cyclooctanols.T he products arise from an exo-mode of cyclization rather than the usual endo-attacke mployed in the few radical syntheses of cyclooctanes.T he process is terminated by the quenching of ac hiral benzylic samarium. Al abeling experiment and neutron diffraction study have been used for the first time to probe the configuration and highly diastereoselective deuteration of ac hiral organosamarium intermediate.

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SmI₂–H₂O-mediated 5-exo/6-exo lactone radical cyclisation cascades

Abstract: The SmI2-H2O reagent system mediates challenging 5-exo/6-exo lactone radical cascade cyclisations that deliver carbo[5.4.0]bicyclic motifs in a diastereoselective, one-pot process that establish two new carbocyclic rings and four stereocentres.

Cited by 15 publications

References 43 publications

Fenton-Inspired C–H Functionalization: Peroxide-Directed C–H Thioetherification

Fenton-Inspired C–H Functionalization: Peroxide-Directed C–H Thioetherification

Sm(II)-Mediated Electron Transfer to Carboxylic Acid Derivatives: Development of Complexity-Generating Cascades

Selective Synthesis of Cyclooctanoids by Radical Cyclization of Seven‐Membered Lactones: Neutron Diffraction Study of the Stereoselective Deuteration of a Chiral Organosamarium Intermediate

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SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades

Abstract: The SmI2-H2O reagent system mediates challenging 5-exo/6-exo lactone radical cascade cyclisations that deliver carbo[5.4.0]bicyclic motifs in a diastereoselective, one-pot process that establish two new carbocyclic rings and four stereocentres.

Cited by 15 publications

References 43 publications

Fenton-Inspired C–H Functionalization: Peroxide-Directed C–H Thioetherification

Fenton-Inspired C–H Functionalization: Peroxide-Directed C–H Thioetherification

Sm(II)-Mediated Electron Transfer to Carboxylic Acid Derivatives: Development of Complexity-Generating Cascades

Selective Synthesis of Cyclooctanoids by Radical Cyclization of Seven‐Membered Lactones: Neutron Diffraction Study of the Stereoselective Deuteration of a Chiral Organosamarium Intermediate

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SmI₂–H₂O-mediated 5-exo/6-exo lactone radical cyclisation cascades