The interplay of structure and reactivity in a most unusual furan diels-alder reaction

J.M. Percy, G.A. Griffith, I.H. Hillier, M.A. Vincent, A.C. Moralee, R. Roig

Research output: Contribution to journalArticle

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Abstract

Difluorinated alkenoate ethyl 3,3-difluoro-2-(N,N-diethylcarbamoyloxy)-2-propenoate reacts rapidly and in high yield with furan and a range of substituted furans in the presence of a tin(IV) catalyst. Non-fluorinated congener 2-(N,N-diethylcarbamoyloxy)-2-propenoate fails to react at all under the same conditions. These reactions have been explored using density functional theory (DFT) calculations. They reveal a highly polar transition state, which is stabilized by the Lewis acid catalyst SnCl4 and by polar solvents. In the presence of both catalyst and solvent, a two-step reaction is predicted, corresponding to the stepwise formation of the two new carbon−carbon bonds via transition states which have similar energies in all cases. Our experimental observations of the lack of reaction of the non-fluorinated dienophile, the stereochemical outcomes, and the rate acceleration accompanying furan methylation are all well predicted by our calculations. The calculated free energy barriers generally correlate well with measured reaction rates, supporting a reaction mechanism in which zwitterionic character is developed strongly. An in situ ring opening reaction of exo-cycloadduct ethyl exo-2-(N,N-diethylcarbamoyloxy)-3,3-difluoro-7-oxabicyclo[2.2.1]hept-5-enyl-2-endo-carboxylate, which results in the formation of cyclic carbonate ethyl 4,4-difluoro-5-hydroxy-2-oxo-5,7a-dihydro-4H-benzo[1,3]dioxole-3a-carboxylate by a Curtin−Hammett mechanism, has also been examined. Substantial steric opposition to Lewis acid binding prevents carbonate formation from 2-substituted furans.
Original languageEnglish
Pages (from-to)13130-13141
Number of pages12
JournalJournal of American Chemical Society
Volume128
Issue number40
DOIs
Publication statusPublished - 2006

Fingerprint

Furans
Lewis Acids
Cycloaddition Reaction
Catalysts
Tin
Carbonates
Methylation
Acids
Energy barriers
Free energy
Reaction rates
Density functional theory
furan
ethyl carbonate
stannic chloride

Keywords

  • furans
  • furan diels-alder reaction

Cite this

Percy, J. M., Griffith, G. A., Hillier, I. H., Vincent, M. A., Moralee, A. C., & Roig, R. (2006). The interplay of structure and reactivity in a most unusual furan diels-alder reaction. Journal of American Chemical Society, 128(40), 13130-13141. https://doi.org/10.1021/ja061458p
Percy, J.M. ; Griffith, G.A. ; Hillier, I.H. ; Vincent, M.A. ; Moralee, A.C. ; Roig, R. / The interplay of structure and reactivity in a most unusual furan diels-alder reaction. In: Journal of American Chemical Society. 2006 ; Vol. 128, No. 40. pp. 13130-13141.
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Percy, JM, Griffith, GA, Hillier, IH, Vincent, MA, Moralee, AC & Roig, R 2006, 'The interplay of structure and reactivity in a most unusual furan diels-alder reaction', Journal of American Chemical Society, vol. 128, no. 40, pp. 13130-13141. https://doi.org/10.1021/ja061458p

The interplay of structure and reactivity in a most unusual furan diels-alder reaction. / Percy, J.M.; Griffith, G.A.; Hillier, I.H.; Vincent, M.A.; Moralee, A.C.; Roig, R.

In: Journal of American Chemical Society, Vol. 128, No. 40, 2006, p. 13130-13141.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The interplay of structure and reactivity in a most unusual furan diels-alder reaction

AU - Percy, J.M.

AU - Griffith, G.A.

AU - Hillier, I.H.

AU - Vincent, M.A.

AU - Moralee, A.C.

AU - Roig, R.

PY - 2006

Y1 - 2006

N2 - Difluorinated alkenoate ethyl 3,3-difluoro-2-(N,N-diethylcarbamoyloxy)-2-propenoate reacts rapidly and in high yield with furan and a range of substituted furans in the presence of a tin(IV) catalyst. Non-fluorinated congener 2-(N,N-diethylcarbamoyloxy)-2-propenoate fails to react at all under the same conditions. These reactions have been explored using density functional theory (DFT) calculations. They reveal a highly polar transition state, which is stabilized by the Lewis acid catalyst SnCl4 and by polar solvents. In the presence of both catalyst and solvent, a two-step reaction is predicted, corresponding to the stepwise formation of the two new carbon−carbon bonds via transition states which have similar energies in all cases. Our experimental observations of the lack of reaction of the non-fluorinated dienophile, the stereochemical outcomes, and the rate acceleration accompanying furan methylation are all well predicted by our calculations. The calculated free energy barriers generally correlate well with measured reaction rates, supporting a reaction mechanism in which zwitterionic character is developed strongly. An in situ ring opening reaction of exo-cycloadduct ethyl exo-2-(N,N-diethylcarbamoyloxy)-3,3-difluoro-7-oxabicyclo[2.2.1]hept-5-enyl-2-endo-carboxylate, which results in the formation of cyclic carbonate ethyl 4,4-difluoro-5-hydroxy-2-oxo-5,7a-dihydro-4H-benzo[1,3]dioxole-3a-carboxylate by a Curtin−Hammett mechanism, has also been examined. Substantial steric opposition to Lewis acid binding prevents carbonate formation from 2-substituted furans.

AB - Difluorinated alkenoate ethyl 3,3-difluoro-2-(N,N-diethylcarbamoyloxy)-2-propenoate reacts rapidly and in high yield with furan and a range of substituted furans in the presence of a tin(IV) catalyst. Non-fluorinated congener 2-(N,N-diethylcarbamoyloxy)-2-propenoate fails to react at all under the same conditions. These reactions have been explored using density functional theory (DFT) calculations. They reveal a highly polar transition state, which is stabilized by the Lewis acid catalyst SnCl4 and by polar solvents. In the presence of both catalyst and solvent, a two-step reaction is predicted, corresponding to the stepwise formation of the two new carbon−carbon bonds via transition states which have similar energies in all cases. Our experimental observations of the lack of reaction of the non-fluorinated dienophile, the stereochemical outcomes, and the rate acceleration accompanying furan methylation are all well predicted by our calculations. The calculated free energy barriers generally correlate well with measured reaction rates, supporting a reaction mechanism in which zwitterionic character is developed strongly. An in situ ring opening reaction of exo-cycloadduct ethyl exo-2-(N,N-diethylcarbamoyloxy)-3,3-difluoro-7-oxabicyclo[2.2.1]hept-5-enyl-2-endo-carboxylate, which results in the formation of cyclic carbonate ethyl 4,4-difluoro-5-hydroxy-2-oxo-5,7a-dihydro-4H-benzo[1,3]dioxole-3a-carboxylate by a Curtin−Hammett mechanism, has also been examined. Substantial steric opposition to Lewis acid binding prevents carbonate formation from 2-substituted furans.

KW - furans

KW - furan diels-alder reaction

UR - http://dx.doi.org/10.1021/ja061458p

U2 - 10.1021/ja061458p

DO - 10.1021/ja061458p

M3 - Article

VL - 128

SP - 13130

EP - 13141

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 40

ER -