Low-Temperature <i>n</i>-Butyllithium-Induced Rearrangement of Allyl 1,1-Dichlorovinyl Ethers

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

doi:10.1021/ol052685j

Cited by 18 publications

(14 citation statements)

References 16 publications

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“…[21] We reasoned that replacement of metallic lithium by organolithium reagents RLi might allow non-terminal alkynes to be prepared in a similar fashion. [22] In fact, treatment of compound 4 as the model substrate with MeLi in Et 2 O resulted in a very clean formation of the corresponding methyl-capped acetylene derivative 5 a (R = Me), but the reaction was slow and excess MeLi had to be used to ensure full conversion (Table 1, entries 1 and 2). The use of THF engendered a much faster rate but led to a slight drop in yield (entry 3).…”

Section: Formation Of Non-terminal Alkynes By Reductive Alkylationmentioning

confidence: 99%

A New Method for the Preparation of Non‐Terminal Alkynes: Application to the Total Syntheses of Tulearin A and C

Lehr

Schulthoff

Ueda

et al. 2014

Chemistry A European J

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Lactones are known to react with the reagent generated in situ from CCl4 and PPh3 in a Wittig-type fashion to give gem-dichloro-olefin derivatives. Such compounds are now shown to undergo reductive alkylation on treatment with organolithium reagents RLi to furnish acetylene derivatives bearing the substituent R at their termini (R=Me, n-, sec-, tert-alkyl, silyl); the reaction can be catalyzed with either Cu(acac)2 or Fe(acac)3 /1,2-diaminobenzene. Two alkynol derivatives prepared in this way from readily accessible lactone precursors served as the key building blocks for the total syntheses of the cytotoxic marine macrolides tulearin A (1) and C (2). The assembly of these fragile targets hinged upon ring closing alkyne metathesis (RCAM) followed by a formal trans-reduction of the resulting cycloalkynes via trans-hydrosilylation/protodesilylation.

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Section: Formation Of Non-terminal Alkynes By Reductive Alkylationmentioning

confidence: 99%

A New Method for the Preparation of Non‐Terminal Alkynes: Application to the Total Syntheses of Tulearin A and C

Lehr

Schulthoff

Ueda

et al. 2014

Chemistry A European J

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“…1–3 Due to their linear geometry, alkynyl ethers are relatively unhindered to approach by functional groups present in the same or different molecules; furthermore, alkynyl ethers can prospectively form up to three new bonds in a single reaction. 4 …”

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confidence: 99%

[3,3]-Sigmatropic Rearrangement/5-exo-digCyclization Reactions of Benzyl Alkynyl Ethers: Synthesis of Substituted 2-Indanones and Indenes

Tudjarian

Minehan

2011

J. Org. Chem.

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Substituted benzyl alkynyl ethers, prepared from the corresponding α-alkoxy ketones in a two-step sequence involving enol triflate formation and KOtBu-induced E2 elimination, undergo [3,3]-sigmatropic rearrangement/intramolecular 5-exo-dig cyclization at 60°C to form substituted 2-indanones in good overall yields. 1,3-cis-disubstituted-2-indanones are formed preferentially when the benzylic substituent R1 is bulky. Substituted indenes may be prepared from 2-indanones in high yields by Horner-Wadsworth-Emmons reaction.

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“…The previous studies of Katzenellenbogen,15 as well as our own investigations,4 have indicated that allyl-1-alkynyl ethers undergo rapid sigmatropic rearrangement at low temperatures (−33 °C, −78 °C) once formed. Therefore, we wished to assess if sigmatropic rearrangement would also take place upon t -BuOK treatment of α-allyloxy ketone-derived vinyl trifates at −78 °C.…”

mentioning

confidence: 68%

“…We have previously shown that treatment of allyl-1,1-dichlorovinyl ethers with 2.2 equiv of n -butyllithium at −78 °C, followed by quenching of the reaction mixture with excess alcohol, leads to rearranged γ,δ-unsaturated esters in high yield 4. The reaction possesses many of the characteristics of a sigmatropic process, both in terms of its stereospecificity and geometrical requirements.…”

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confidence: 99%

Synthesis of Alkynyl Ethers and Low-Temperature Sigmatropic Rearrangement of Allyl and Benzyl Alkynyl Ethers

2008

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Abstractα-Alkoxy ketones 3 can be transformed into 1-alkynyl ethers 5 by a two-step procedure involving formation of the enol triflate or phosphate and base-induced elimination. Performing the same reaction sequence with allylic alcohols (R 2 OH, R 2 = allyl) furnishes instead γ,δ-unsaturated carboxylic acid derivatives 6, derived from [3,3]-sigmatropic rearrangement of the intermediate allyl alkynyl ethers at −78 °C and trapping of the subsequently formed ketene with nucleophiles (Nu-H). Benzyl alkynyl ether 5 (R 2 = benzyl) rearranges to indanone 7 upon heating to 60 °C.Electron-rich alkynes, such as ynamines and ynol ethers, are functional groups that possess significant potential in organic chemistry for the formation of carbon-carbon bonds. 1 The synthetic utility of ynamides has been considerably expanded recently, along with the development of new methods for their facile preparation from simple building blocks. 2 1-Alkynyl ethers, while possessing many of the reactivity features of ynamides, have been far less investigated due to the relatively few methods currently available for their synthesis. 3 In this letter we present a mild and efficient method for the synthesis of diverse 1-alkynyl ethers and demonstrate that a facile sigmatropic rearrangement of allyl and benzyl alkynyl ethers furnishes products containing new carbon-carbon bonds.We have previously shown that treatment of allyl-1,1-dichlorovinyl ethers with 2.2 equiv of n-butyllithium at −78 °C, followed by quenching of the reaction mixture with excess alcohol, leads to rearranged γ,δ-unsaturated esters in high yield. 4 The reaction possesses many of the characteristics of a sigmatropic process, both in terms of its stereospecificity and geometrical requirements. We have proposed that an initially generated allyl alkynyl ether intermediate undergoes a [3,3]-sigmatropic rearrangement either as a neutral or as a negatively charged species.Due to its reactivity toward a range of functional groups, the use of the nucleophilic base nBuLi to generate the key intermediate in this reaction may be viewed as a potential limitation. Furthermore, the preparation of the allyl-1,1-dichlorovinyl ether substrate via methylenation of an allylic formate ester requires the use of toxic carbon tetrachloride in combination with triphenylphosphine. Since terminal and internal alkynes have been previously prepared from ketones by treatment of the corresponding enol phosphates or triflates with a non-nucleophilic base, 5 we sought to investigate the preparation of 1-alkynyl ethers from α-alkoxy ketones via E2 elimination of the derived enol triflates or phosphates.Following the procedure of Muthusamy et. al., 6 treatment of a toluene solution of diazoacetophenone 1a and menthol with a catalytic amount (10 mol %) of indium triflate at room temperature furnished α-alkoxy ketone 3a in 91% yield (Scheme 1). Formation of the enol triflate was achieved by stirring 3a with LiHMDS at −78 °C for one hour, followed by quenching with PhNTf 2 in DMPU/THF (1:2) and warming to room ...

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Low-Temperature n-Butyllithium-Induced Rearrangement of Allyl 1,1-Dichlorovinyl Ethers

Cited by 18 publications

References 16 publications

A New Method for the Preparation of Non‐Terminal Alkynes: Application to the Total Syntheses of Tulearin A and C

A New Method for the Preparation of Non‐Terminal Alkynes: Application to the Total Syntheses of Tulearin A and C

[3,3]-Sigmatropic Rearrangement/5-exo-digCyclization Reactions of Benzyl Alkynyl Ethers: Synthesis of Substituted 2-Indanones and Indenes

Synthesis of Alkynyl Ethers and Low-Temperature Sigmatropic Rearrangement of Allyl and Benzyl Alkynyl Ethers

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