Facile Dehydration of Activated Ketones to Alkynes

Hendrickson, James B.; Hussoin, M. S.

doi:10.1055/s-1989-27207

Cited by 18 publications

(3 citation statements)

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“…9 The reagent was prepared in situ as usual in 1,2-dichloroethane and treated with an equimolar amount of the ketone and two equivalents of Et 3 N and the mixture refluxed for an hour. When the ketone was activated by an adjacent carbonyl in R 2 , the reaction proceeded to completion within an hour (Entries 1-4).…”

Section: Conversion Of Activated Ketones To Alkynesmentioning

confidence: 99%

The Hendrickson ‘POP’ reagent and analogues thereof: synthesis, structure, and application in organic synthesis

Moussa¹

2012

Arkivoc

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This comprehensive review discusses the synthesis, structure, and application of the Hendrickson 'POP' reagent and its analogues in organic synthesis. Specifically, the review describes applications of the preceding dehydrating agents in functional group interconversions, heterocycle synthesis, and total synthesis of natural products. Many examples are provided from the literature to show the scope and selectivity (regio and chemo) in these transformations.

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Section: Conversion Of Activated Ketones To Alkynesmentioning

confidence: 99%

The Hendrickson ‘POP’ reagent and analogues thereof: synthesis, structure, and application in organic synthesis

Moussa¹

2012

Arkivoc

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“…We successfully have used 2, N -bistriisopropylsilyl-1,3-butadiene ketenimine ( 1) and methyl 2-butynoate in the synthesis of anthranilic acid . For our biochemical studies it was necessary to introduce 13 C-labeling in the aromatic core, but when we approached the synthesis of benzyl (1,2,3,4- 13 C 4 )-2-butynoate using a reported procedure, the compound we obtained instead was the corresponding allene isomer 2 . However, we envisioned that these allenes could also be used as the dienophile partners in a Diels−Alder reaction with vinyl ketenimine in order to obtained substituted anilines.…”

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confidence: 99%

Preparation of ¹³C₄-6-Methyl Anthranilic Ester via a Diels−Alder-Type Process. An Experimental and Theoretical Study to Characterize an Unexpected Isotope Exchange

et al. 2005

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Buta-2,3-dienoate reacts with vinyl ketenimine to give the corresponding substituted aniline through a Diels-Alder cycloaddition. Besides the expected Diels-Alder adduct 3a, the aniline 3b was also obtained in a ratio of 91:9. The observed (13)C exchange is explained on the basis of a reversible [2 + 2] cycloaddition competing with the [4 + 2] process. This is supported by B3LYP DFT computations, as a stepwise pathway lies very close in energy to the [4 + 2] concerted one. [reaction: see text]

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“…6,7 Thus, methyl 4-fluorobenzoylacetate 1 was dehydrated to the alkynyl ester 2 in good yield. 8 Other methods for the production of 2, e.g. Pd-catalysed coupling of 1-iodo-4-fluorobenzene and TMS-acetylene, followed by lithiation and quenching with methyl chloroformate, 9 were successful but gave lower overall yields.…”

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confidence: 99%

Regioselective Rapid Analogue Syntheses of 1-Methyl-3,5-diarylpyrazoles via Palladium-catalysed Coupling to 3(5)-Pyrazolyl Nonaflates

Bourrain¹,

Ridgill²,

Collins³

2004

Synlett

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Regioselective rapid analogue syntheses of 1-methyl-3,5-diarylpyrazoles were developed, based on Pd-catalysed couplings to 1-methyl-3(5)-arylpyrazole nonaflates, which offered an advantage in hydrolytic stability over the corresponding triflates. The new bifunctional reagent 1-methyl-3-bromo-pyrazol-5-yl nonaflate underwent highly chemoselective Pd-catalysed couplings to the nonaflate, followed by Suzuki couplings to the bromide, allowing sequential, regioselective introduction of the two aryl substituents.Substituted pyrazoles are important constituents of biologically active synthetic compounds. 2 As part of a medicinal chemistry program, we required an efficient, regioselective synthetic route to variously substituted 1-methyl-3,5-diarylpyrazoles. In particular, we wished to be able to introduce 1-methyl-3(5)-arylpyrazole moieties to more complex substituted arylboronates using palladiumcatalysed cross-couplings at a late stage in the sequence. There are many reported methods for the regioselective formation of N-alkyl pyrazoles 2 and recently methods have become available for Pd-catalysed cross-couplings to N-alkyl-and N-aryl-3(5)-halopyrazoles. 3,4 Descriptions of cross-coupling reactions to pyrazole trifluoromethanesulfonates (triflates) 5 are scarce, however, and there are no reports concerning pyrazole nonafluorobutanesulfonates (nonaflates).Our initial studies targeted 3-and 5-(4-fluorophenyl)pyrazoles. The condensation of methylhydrazine with methyl 4-fluorobenzoylacetate 1 gave predominantly a single pyrazole 3, 6 which was conveniently isolated in pure form by crystallisation from the reaction mixture (43% yield). Column chromatography of the mother liquors allowed the isolation of further pure product 3 (41%) and a minor product 4 (4%, Scheme 1). The regiochemistry of the minor product was demonstrated by the observed NOE between the N-methyl group and the fluoroaromatic ring ( Figure 1). To prepare synthetically useful quantities of the regioisomer 4, the alternative cyclocondensation of methylhydrazine and b-arylacetylenic esters was investigated. 6,7 Thus, methyl 4-fluorobenzoylacetate 1 was dehydrated to the alkynyl ester 2 in good yield. 8 Other methods for the production of 2, e.g. Pd-catalysed coupling of 1-iodo-4-fluorobenzene and TMS-acetylene, followed by lithiation and quenching with methyl chloroformate, 9 were successful but gave lower overall yields. The reaction of ethyl phenylpropionate and MeNHNH 2 in aqueous MeOH is known to give a mixture of pyazoles where the regiochemistry corresponding to 3 dominates. 7a However, the reaction of the methyl ester is reported to lead to the alternative regioisomer. 7b In agreement with this, the methyl ester 2 gave predominantly the desired pyrazole 4 on treatment with MeNHNH 2 in warm aqueous EtOH (4:3 ca. 2:1 in crude mixture). A strong effect of the size of the ester group on the regioselectivity of the condensation Scheme 1 Reaction conditions: (a) NH 2 NHMe, MeOH, r.t.; (b) Ph 3 P=O, (CF 3 CO) 2 O, Et 3 N, 1,2-dichloroethane, 0°C, reflux; (c)...

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Facile Dehydration of Activated Ketones to Alkynes

Cited by 18 publications

References 0 publications

The Hendrickson ‘POP’ reagent and analogues thereof: synthesis, structure, and application in organic synthesis

The Hendrickson ‘POP’ reagent and analogues thereof: synthesis, structure, and application in organic synthesis

Preparation of ¹³C₄-6-Methyl Anthranilic Ester via a Diels−Alder-Type Process. An Experimental and Theoretical Study to Characterize an Unexpected Isotope Exchange

Regioselective Rapid Analogue Syntheses of 1-Methyl-3,5-diarylpyrazoles via Palladium-catalysed Coupling to 3(5)-Pyrazolyl Nonaflates

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Facile Dehydration of Activated Ketones to Alkynes

Cited by 18 publications

References 0 publications

The Hendrickson ‘POP’ reagent and analogues thereof: synthesis, structure, and application in organic synthesis

The Hendrickson ‘POP’ reagent and analogues thereof: synthesis, structure, and application in organic synthesis

Preparation of 13C4-6-Methyl Anthranilic Ester via a Diels−Alder-Type Process. An Experimental and Theoretical Study to Characterize an Unexpected Isotope Exchange

Regioselective Rapid Analogue Syntheses of 1-Methyl-3,5-diarylpyrazoles via Palladium-catalysed Coupling to 3(5)-Pyrazolyl Nonaflates

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Preparation of ¹³C₄-6-Methyl Anthranilic Ester via a Diels−Alder-Type Process. An Experimental and Theoretical Study to Characterize an Unexpected Isotope Exchange