Thermal reactions of cyclopropenone ketals.  Key mechanistic features and scope of the cycloaddition reactions of delocalized singlet vinylcarbenes:  three-carbon 1,1-/1,3-dipoles

Boger, Dale L.; Brotherton, Christine E.

doi:10.1021/ja00281a041

Cited by 106 publications

(59 citation statements)

References 3 publications

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“…According to the above results, we proposed that the side product 4a may arise from hydrogen fluoride-promoted ring-opening of a cyclopropenone acetal intermediate II that is in equilibrium with an alkoxycyclopropenium cation intermediate I (Fig. 2a)404142. The occurrence of the cyclopropenone acetal pathway (path b) is attributed to the weak nucleophilicity of fluoride ion.…”

Section: Resultsmentioning

confidence: 89%

“…When CpFluor 1 with less electron-rich substituents, such as phenyl group undergoes the reaction (path b), the formed less stable intermediate I further reacts with monoalcohols to give cyclopropenone acetal II as the more stable intermediate. The so-formed intermediate II is in equilibrium with intermediate I under the action of hydrogen fluoride and readily undergoes thermal-induced ring-opening reaction to give vinylcarben intermediate III (refs 40, 41, 42). Protonation of the vinylcarbene III by hydrogen fluoride followed by a fluoride attack delivers a mixture of alkyl fluoride 3 and acrylate 4 .…”

Section: Resultsmentioning

confidence: 99%

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Deoxyfluorination of alcohols with 3,3-difluoro-1,2-diarylcyclopropenes

Wang

et al. 2016

Nat Commun

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Aromatic cation activation is a useful strategy to promote deoxyfunctionalization; however, the deoxyfluorination of alcohols with cyclopropenium cation remains an unsolved problem due to the weak nucleophilicity of fluoride ion. Here we report the use of 3,3-difluoro-1,2-diarylcyclopropenes (CpFluors) as easily accessible and reactivity-tunable deoxyfluorination reagents. The electronic nature of CpFluors is critical for fluorination of monoalcohols via alkoxycyclopropenium cations, and CpFluors with electron-rich aryl substituents facilitate the transformation with high efficiency; however, selective monofluorination of 1,2- and 1,3-diols, which proceeds via cyclopropenone acetals, is less dependent on the electronic nature of CpFluors. Moreover, CpFluors are more sensitive to the electronic nature of alcohols than many other deoxyfluorination reagents, thus fluorination of longer diols can be achieved selectively at the relatively electron-rich position. This research not only unveils the first example of deoxyfluorination reagents that contain an all-carbon scaffold, but also sheds light on the divergent reactivity of cyclopropenium cation in deoxyfunctionalization of alcohols.

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Section: Resultsmentioning

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Deoxyfluorination of alcohols with 3,3-difluoro-1,2-diarylcyclopropenes

Wang

et al. 2016

Nat Commun

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“…Many heterocyclic systems such as 1,8-naphthyridines, 2H-pyrido[1,2-a]pyrimidin-4-ones, pyrazolinones, pyrons, xanthyrones, guanidine derivatives, 1,2,4-triazoles, 3-oxo-1,2,6-thiadiazines, 8-oxoimidazo [1,2a]pyrimidines, 3H-pyrrolo [1,2-a]indol-3-one derivatives and 1H-1,4-benzodiazepines have been obtained using EMME as synthon [2]. EMME is widely used in push-pull alkane [3], 1,4-addition elimination [4], 1,4 addition [5], [3+2] cycloadditions [6], Diels-Alder reactions [8] and extensively reviewed as Michael reagent [7]. Dave et al [9,10] reported a novel route for the synthesis of pyrido [3,2-e]pyrimido [1,2c]pyrimidines and thieno[3,2-e]pyrimido[1,2-c]pyrimidines using the same synthon.…”

Section: Introductionmentioning

confidence: 99%

The gould-jacob type of reaction for the synthesis of novel pyrimidopyrrolopyrimidines: A comparison of classical heatingvssolvent free microwave irradiation

Desai

2006

Journal of Heterocyclic Chemistry

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The Gould-Jacob type of reaction for the synthesis of ethyl 4-oxo-8, 10-substituted-4,8-dihydropyrimido[1,2c]pyrrolo [3,2-e]pyrimidine-3-carboxylates 5 has been carried out conventionally by the condensation between 4aminopyrrolo[2,3-d]pyrimidines 2 and diethyl ethoxymethylenemalonate 3 via acyclic intermediates diethyl N- [5,7-substituted-7H-pyrrolo[2,3-d]pyrimidin-4-yl]aminomethylenemalonates 4 and the results obtained were compared with single step microwave irradiation under solvent free conditions for the synthesis of 5.

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“…This resulted in the discovery of the thermal [1 + 2],2 [3 + 2],3 and [3 + 4]4 cycloaddition reactions of singlet π-delocalized vinylcarbenes that complement the [4 + 2]5 cycloaddition reactions of the cyclopropenone ketals themselves, providing a rich series of reactions whose course could be controlled by a combination of the choice of substrate and the reaction conditions (Figure 1). 1,6…”

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confidence: 99%

Intramolecular [1 + 2] and [3 + 2] Cycloaddition Reactions of Cyclopropenone Ketals

Patel

Boger

2010

J. Am. Chem. Soc.

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The first intramolecular thermal reactions of cyclopropenone ketals are reported enlisting substrates tethered to an electron-deficient olefin bearing a single electron-withdrawing substituent. Whereas the intermolecular variants of the reactions provide only the products of an endo selective [1 + 2] cycloaddition or a carbonyl addition reaction of a thermally generated π-delocalized singlet vinylcarbene, the intramolecular variants provide either [1 + 2] or [3 + 2] cycloadducts in reactions that depend on the reaction conditions, the alkene activating substituent, and the nature of the tethering. In addition to providing key mechanistic insights into the thermal [3 + 2] cycloaddition reaction for such substrates, they were also found to proceed under conditions that reflect the ease and regioselectivity of the cyclopropenone ketal cleavage for π-delocalized singlet vinylcarbene generation. The most effective combination of structural features that impact the reactivity was observed with substrates bearing an aldehyde or ketone substituted electron-deficient olefin and incorporating an aryl cyclopropenone ketal substituent built into the linking tether. Simply warming a solution of such substrates in toluene at 80-100 °C directly provided the [3 + 2] cycloadducts in excellent yield (60-88%) under mild thermal reaction conditions.The disclosure of the reversible thermal generation of π-delocalized singlet vinylcarbenes from cyclopropenone ketals first emerged from an examination of the cycloaddition reactions of the parent unsubstituted cyclopropenone ketals.1 This resulted in the discovery of the thermal [1 + 2],2 [3 + 2],3 and [3 + 4]4 cycloaddition reactions of singlet π-delocalized vinylcarbenes that complement the [4 + 2]5 cycloaddition reactions of the cyclopropenone ketals themselves, providing a rich series of reactions whose course could be controlled by a combination of the choice of substrate and the reaction conditions ( Figure 1).1 , 6A key element to emerge from the studies was the reversibility of the thermal π-delocalized singlet vinylcarbene generation that insures its eventual productive trap by an electrondeficient substrate. In preceding studies, only intermolecular cycloadditions were examined with a focus on understanding the underlying mechanistic questions posed by the observed reactions.1 , 6 Herein, we report the first intramolecular thermal cycloaddition reactions of cyclopropenone ketals that permit the nature of the substrate tethering and the stereoelectronic (orbital alignment) features of the reactions to control the reaction course providing additional mechanistic insights into these unique thermal reactions. Examined ] cycloadducts in reactions that depend on the reaction conditions, the alkene activating substituent, and the nature of the tethering. In addition to providing key mechanistic insights into the thermal [3 + 2] cycloaddition, they were also found to proceed under conditions that reflect the ease and regioselectivity of the cyclopropenone ketal cleavage7...

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Thermal reactions of cyclopropenone ketals. Key mechanistic features and scope of the cycloaddition reactions of delocalized singlet vinylcarbenes: three-carbon 1,1-/1,3-dipoles

Cited by 106 publications

References 3 publications

Deoxyfluorination of alcohols with 3,3-difluoro-1,2-diarylcyclopropenes

Deoxyfluorination of alcohols with 3,3-difluoro-1,2-diarylcyclopropenes

The gould-jacob type of reaction for the synthesis of novel pyrimidopyrrolopyrimidines: A comparison of classical heatingvssolvent free microwave irradiation

Intramolecular [1 + 2] and [3 + 2] Cycloaddition Reactions of Cyclopropenone Ketals

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