Low temperature n-butyllithium-induced [3,3]-sigmatropic rearrangement/electrophile trapping reactions of allyl-1,1-dichlorovinyl ethers. Synthesis of β-, γ- and δ-lactones

Christopher, Aaron; Brandes, Dahniel; Kelly, Stephen; Minehan, Thomas G.

doi:10.1039/c3ob41777h

Cited by 6 publications

(6 citation statements)

References 26 publications

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“…Indeed, treatment of vinyl ether 2c with n-BuLi at −78 °C followed by methyl triflate or TMSCl (2 equiv) and then excess ethanol gave rise to α-substituted unsaturated esters in good yields, albeit with poor diastereoselectivity (Scheme 6). It was subsequently discovered that addition of symmetrical or unsymmetrical ketones to the anionic rearrangement mixture at −78 °C, followed by quench with saturated aqueous bicarbonate solution instead of alcohols, gave rise to β-lactones (20) in high overall yields. 20 Interestingly, the use of aldehydes in this reaction instead gave only low yields of the corresponding β-hydroxy acids.…”

Section: [33]-sigmatropic Rearrangement Of Allylmentioning

confidence: 99%

“…It was subsequently discovered that addition of symmetrical or unsymmetrical ketones to the anionic rearrangement mixture at −78 °C, followed by quench with saturated aqueous bicarbonate solution instead of alcohols, gave rise to β-lactones (20) in high overall yields. 20 Interestingly, the use of aldehydes in this reaction instead gave only low yields of the corresponding β-hydroxy acids. These results indicate the importance of the newly formed quaternary center for efficient cyclization of the presumed β-hydroxy ketene intermediate at low temperatures.…”

Section: [33]-sigmatropic Rearrangement Of Allylmentioning

confidence: 99%

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Tandem Bond-Forming Reactions of 1-Alkynyl Ethers

Minehan

2016

Acc. Chem. Res.

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Electron-rich alkynes, such as ynamines, ynamides, and ynol ethers, are functional groups that possess significant potential in organic chemistry for the formation of carbon-carbon bonds. While the synthetic utility of ynamides has recently been expanded considerably, 1-alkynyl ethers, which possess many of the reactivity features of ynamides, have traditionally been far less investigated because of concerns about their stability. Like ynamides, ynol ethers are relatively unhindered to approach by functional groups present in the same or different molecules because of their linear geometry, and they can potentially form up to four new bonds in a single transformation. Ynol ethers also possess unique reactivity features that make them complementary to ynamides. Research over the past decade has shown that ynol ethers formed in situ from stable precursors engage in a variety of useful carbon-carbon bond-forming processes. Upon formation at -78 °C, allyl alkynyl ethers undergo a rapid [3,3]-sigmatropic rearrangement to form allyl ketene intermediates, which may be trapped with alcohol or amine nucleophiles to form γ,δ-unsaturated carboxylic acid derivatives. The process is stereospecific, takes place in minutes at cryogenic temperatures, and affords products containing (quaternary) stereogenic carbon atoms. Trapping of the intermediate allyl ketene with carbonyl compounds, epoxides, or oxetanes instead leads to complex α-functionalized β-, γ-, or δ-lactones, respectively. [3,3]-Sigmatropic rearrangement of benzyl alkynyl ethers also takes place at temperatures ranging from -78 to 60 °C to afford substituted 2-indanones via intramolecular carbocyclization of the ketene intermediate. tert-Butyl alkynyl ethers containing pendant di- and trisubstituted alkenes and enol ethers are stable to chromatographic isolation and undergo a retro-ene/[2 + 2] cycloaddition reaction upon mild thermolysis (90 °C) to afford cis-fused cyclobutanones and donor-acceptor cyclobutanones in good to excellent yields and diastereoselectivities. This process, which takes place under neutral conditions and proceeds through an aldoketene intermediate, obviates the need to employ moisture-sensitive and/or unstable acid chlorides under basic conditions for intramolecular [2 + 2] cycloaddition reactions. Furthermore, Lewis acid-catalyzed intramolecular condensations of both ethyl and tert-butyl ynol ethers with tethered acetals efficiently provide protected five-, six-, and seven-membered cyclic Baylis-Hilman adducts. Metalated ethoxyacetylene can also participate in multiple bond-forming reactions that avoid isolation of the alkynyl ether intermediate. Lewis acid-promoted tandem additions employing epoxides/oxetanes and carbonyl compounds give rise to (Z)-α-alkylidene and α-benzylidene lactones stereoselectively in high overall yields. Three new carbon-carbon bonds and a ring are formed in this atom-economical single-flask transformation, resulting in a significant increase in molecular complexity. This Account provides a detailed overview of these...

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Section: [33]-sigmatropic Rearrangement Of Allylmentioning

confidence: 99%

Section: [33]-sigmatropic Rearrangement Of Allylmentioning

confidence: 99%

Tandem Bond-Forming Reactions of 1-Alkynyl Ethers

Minehan

2016

Acc. Chem. Res.

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“…Subsequently it was discovered that quenching the reaction with acetone in place of methanol gave rise to the corresponding rearranged β-lactones 5 (R 2 = R 3 = Me). 5 These results indicated that the species generated after [3,3]-sigmatropic rearrangement may undergo either protonation and intermolecular nucleophilic ketene trapping with alcohols or [2 + 2] cycloaddition with carbonyl compounds and protonation to provide the observed products. A likely candidate for this intermediate species is the lithium ynolate, a functional group that has been shown by Schollkopf 6 to interact with carbonyl compounds at low temperatures to provide β-lactone products in good yields.…”

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confidence: 91%

“…Thus, treatment of 1 with n -butyllithium (2.2 equiv) at −78 °C, followed by reaction quench with methanol, affords 3,4-unsaturated methyl esters 6 in good overall yields. Subsequently it was discovered that quenching the reaction with acetone in place of methanol gave rise to the corresponding rearranged β-lactones 5 (R 2 = R 3 = Me) . These results indicated that the species generated after [3,3]-sigmatropic rearrangement may undergo either protonation and intermolecular nucleophilic ketene trapping with alcohols or [2 + 2] cycloaddition with carbonyl compounds and protonation to provide the observed products.…”

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confidence: 99%

n-Butyllithium-Induced Tandem [3,3]-Sigmatropic Rearrangement and Carbonyl Olefination of Allyl-1,1-dichlorovinyl Ethers

et al. 2021

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Exposure of dichlorovinyl ethers 1 to n-butyllithium and addition of saturated or unsaturated aldehydes, ketones, or esters at ambient temperature furnishes rearranged α,β-unsaturated carboxylic acids, isolated as their corresponding methyl esters 2 in 48–91% overall yields. Exposure of dichlorovinyl ethers 1 to n-butyllithium, addition of aldehydes, ketones, dialdehydes, or diketones at −78 °C, and warming to 80 °C in the presence of SiO2 provide 1,4-dienes 3 or cycloalken-1-ols (or their dehydration products) 4 in 45–72% overall yields.

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“…18 Minehan showed that the reactive intermediates obtained from n-BuLi-induced rearrangement of allyl 1,1dichlorovinyl ethers can be successfully intercepted by oxetanes to cleanly provide δ-lactones. 19 Overall, the ring-expansion reactions described above provide access to new, usefully functionalized heterocycles. In the cases where the oxetanes are readily accessible, the approaches represent efficient access to these systems.…”

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confidence: 99%