Electrooxidative Coupling of Furans and Silyl Enol Ethers:  Application to the Synthesis of Annulated Furans

Sperry, Jeffrey B.; Whitehead, Christopher R.; Ghiviriga, Ion; Walczak, Ryan M.; Wright, Dennis L.

doi:10.1021/jo049889i

Cited by 65 publications

(24 citation statements)

References 38 publications

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“…EC provides relatively clean samples and has shown to facilitate the formation of interesting molecules for drug research [19]. The p38α mitogen-activated protein kinase (p38α kinase) is a prominent example of a drug target kinase [20] and is heavily involved in inflammation processes [21].…”

Section: Introductionmentioning

confidence: 99%

On-line electrochemistry–bioaffinity screening with parallel HR-LC-MS for the generation and characterization of modified p38α kinase inhibitors

Falck¹,

Vlieger²,

Giera³

et al. 2012

Anal Bioanal Chem

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In this study, an integrated approach is developed for the formation, identification and biological characterization of electrochemical conversion products of p38α mitogen-activated protein kinase inhibitors. This work demonstrates the hyphenation of an electrochemical reaction cell with a continuous-flow bioaffinity assay and parallel LC-HR-MS. Competition of the formed products with a tracer (SKF-86002) that shows fluorescence enhancement in the orthosteric binding site of the p38α kinase is the readout for bioaffinity. Parallel HR-MSn experiments provided information on the identity of binders and non-binders. Finally, the data produced with this on-line system were compared to electrochemical conversion products generated off-line. The electrochemical conversion of 1-{6-chloro-5-[(2R,5S)-4-(4-fluorobenzyl)-2,5-dimethylpiperazine-1-carbonyl]-3aH-indol-3-yl}-2-morpholinoethane-1,2-dione resulted in eight products, three of which showed bioaffinity in the continuous-flow p38α bioaffinity assay used. Electrochemical conversion of BIRB796 resulted, amongst others, in the formation of the reactive quinoneimine structure and its corresponding hydroquinone. Both products were detected in the p38α bioaffinity assay, which indicates binding to the p38α kinase.Electronic supplementary materialThe online version of this article (doi:10.1007/s00216-011-5663-2) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

On-line electrochemistry–bioaffinity screening with parallel HR-LC-MS for the generation and characterization of modified p38α kinase inhibitors

Falck¹,

Vlieger²,

Giera³

et al. 2012

Anal Bioanal Chem

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“…797 Heteroaromatic rings are also compatible coupling partners in these intramolecular anodic olefin coupling reactions. Here, different tethers can be employed to afford, for example, six-(Scheme 96) 794,796,798,799 or seven-membered 800 (Scheme 97) annulated furan systems, which can be readily transformed into various carbo-and oxacyclic motifs. [801][802][803][804][805][806][807] These electrochemical annulations are presumed to involve initial oxidation of the silyl enol ether moiety rather than the furyl group.…”

Section: Electrochemical Oxidative Cross-couplingsmentioning

confidence: 99%

Electrochemical strategies for C–H functionalization and C–N bond formation

2018

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Conventional methods for carrying out carbon-hydrogen functionalization and carbon-nitrogen bond formation are typically conducted at elevated temperatures, and rely on expensive catalysts as well as the use of stoichiometric, and perhaps toxic, oxidants. In this regard, electrochemical synthesis has recently been recognized as a sustainable and scalable strategy for the construction of challenging carbon-carbon and carbon-heteroatom bonds. Here, electrosynthesis has proven to be an environmentally benign, highly effective and versatile platform for achieving a wide range of nonclassical bond disconnections via generation of radical intermediates under mild reaction conditions. This review provides an overview on the use of anodic electrochemical methods for expediting the development of carbon-hydrogen functionalization and carbon-nitrogen bond formation strategies. Emphasis is placed on methodology development and mechanistic insight and aims to provide inspiration for future synthetic applications in the field of electrosynthesis.

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“…In one path, the presence of the spiro-fused 3-furanone makes it an attractive target for an electrochemical annulation strategy through oxidative cyclization of 2 . We have worked extensively with furan-terminating electrochemical oxidative cyclizations and this method has been successful in the formation of 5-, 6-, and 7-membered carbocycles [ 4 , 5 , 6 , 7 ]. In a parallel approach to the anodic oxidation, a sequential furan Diels-Alder reaction to give 3 , followed by a ring opening metathesis/ring closing metathesis (ROM/RCM) process could also deliver the target intermediate, a strategy we have recently employed in an approach to cyclopamine [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

The Tandem Ring Opening/Ring Closing Metathesis Route to Oxaspirocycles: An Approach to Phelligridin G

Cooper

Wright

2013

Molecules

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Phelligridin G is an unusual natural product that contains an embedded spiro-fused furanone core. We have investigated two furan-based synthetic approaches towards the spirocyclic core structure of this natural product from readily available 2-phenylfurans. Although initial studies involving an oxidative cyclization were unsuccessful, we were ultimately able to access this key system through a sequential intermolecular furan Diels-Alder reaction followed by a metathesis-based reorganization. A related approach led to an expanded C ring to form spiro-fused pyran spirocycles.

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Electrooxidative Coupling of Furans and Silyl Enol Ethers: Application to the Synthesis of Annulated Furans

Cited by 65 publications

References 38 publications

On-line electrochemistry–bioaffinity screening with parallel HR-LC-MS for the generation and characterization of modified p38α kinase inhibitors

On-line electrochemistry–bioaffinity screening with parallel HR-LC-MS for the generation and characterization of modified p38α kinase inhibitors

Electrochemical strategies for C–H functionalization and C–N bond formation

The Tandem Ring Opening/Ring Closing Metathesis Route to Oxaspirocycles: An Approach to Phelligridin G

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