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Carreira has developed a route to the corresponding cyclopentane in the axinellimines that would be applicable to the synthesis of the revised structure of palau'amine. See: Starr, J. T.; Koch, G.; Carreira, E. M. J. Am. Chem. Soc. 2000, 122, 8793.
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37549036872
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Exo/endo-selectivity varied from 0.8 to 1.1:1.0 when using toluene, dichloromethane, chloroform, acetone, acetonitrile, nitromethane, tert-butyl alcohol, or water as solvent. No obvious correlation of diastereoselectivity to solvent dielectric constant was observed. For a full table of results, see the Supporting Information.
-
Exo/endo-selectivity varied from 0.8 to 1.1:1.0 when using toluene, dichloromethane, chloroform, acetone, acetonitrile, nitromethane, tert-butyl alcohol, or water as solvent. No obvious correlation of diastereoselectivity to solvent dielectric constant was observed. For a full table of results, see the Supporting Information.
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37549015061
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37549072808
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All transition states were characterized by frequency calculations and shown to have a single negative eigenvalue
-
All transition states were characterized by frequency calculations and shown to have a single negative eigenvalue.
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-
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35
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84986513567
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Charge analysis, using the CHelpG method (Breneman, C. M.; Wiberg, K. B. J. Comput. Chem. 1990, 11, 361), indicated a charge buildup of +0.31 on the diene.
-
Charge analysis, using the CHelpG method (Breneman, C. M.; Wiberg, K. B. J. Comput. Chem. 1990, 11, 361), indicated a charge buildup of +0.31 on the diene.
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-
36
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37549068702
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Control experiments on several Diels-Alder adducts showed no sign of reversibility. In combination with the fact that the reactions are exothermic, the cycloadditions were assumed to be under kinetic control
-
Control experiments on several Diels-Alder adducts showed no sign of reversibility. In combination with the fact that the reactions are exothermic, the cycloadditions were assumed to be under kinetic control.
-
-
-
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37
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37549029941
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α,β-unsaturated thiocarbonyls are known to be excellent dienes. See: Boger, D. L. Comprehensive Organic Synthesis; Trost, B. M.; Fleming, I.; Paquette, L. A., Eds.; Pergamon: Oxford 1991; 5, pp 451-512.
-
α,β-unsaturated thiocarbonyls are known to be excellent dienes. See: Boger, D. L. Comprehensive Organic Synthesis; Trost, B. M.; Fleming, I.; Paquette, L. A., Eds.; Pergamon: Oxford 1991; Vol. 5, pp 451-512.
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38
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33947369742
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See Supporting Information for synthesis of 22
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Cernak, T. A.; Gleason, J. L. Heterocycles 2007, 71, 117. See Supporting Information for synthesis of 22.
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Cernak, T.A.1
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39
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37549070082
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Cycloadditions were generally devoid of side products. Isolated yields were difficult to obtain for hydantoin and thiohydantoin dienophiles due to consistent comigration of unreacted dienophile and cycloadduct upon silica gel chromatography. Pure cycloadducts were obtained either by exhaustive cycloaddition in the presence of an excess of cyclopentadiene or by accepting losses on chromatography. See Supporting Information for details on individual compounds
-
Cycloadditions were generally devoid of side products. Isolated yields were difficult to obtain for hydantoin and thiohydantoin dienophiles due to consistent comigration of unreacted dienophile and cycloadduct upon silica gel chromatography. Pure cycloadducts were obtained either by exhaustive cycloaddition in the presence of an excess of cyclopentadiene or by accepting losses on chromatography. See Supporting Information for details on individual compounds.
-
-
-
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40
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37549060138
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Higher temperatures resulted in thermal Boc deprotection
-
Higher temperatures resulted in thermal Boc deprotection.
-
-
-
-
41
-
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37549032287
-
-
2O) in the DFT calculations using the standard PCM method did not alter significantly either relative reactivity between dienophiles nor exo/endo selectivity.
-
2O) in the DFT calculations using the standard PCM method did not alter significantly either relative reactivity between dienophiles nor exo/endo selectivity.
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42
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20344388819
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Glendening, E. D, Reed, A. E, Carpenter, J. E, Weinhold, F. NBO, version 3.1
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55
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37549039239
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C=O 71-2 kcal/mol (thiohydantoin), 74.8 kcal/mol (hydantoin).
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C=O 71-2 kcal/mol (thiohydantoin), 74.8 kcal/mol (hydantoin).
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56
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37549037652
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Evans has noted the increased dienophilicity of thiazolidine thionyl acrylates compared to oxazolidinyl acrylates in copper-catalyzed Diels-Alder reactions, although in that case the difference in rates was attributed to the greater affinity of sulfur-based dienophiles for CuII Lewis acids. See ref 25b
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II Lewis acids. See ref 25b.
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66
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37549055228
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A referee noted the possibility for a C-H⋯O interaction between the methylene of cyclopentadiene and carbonyl oxygens in the exo-transition states. Weak C-H⋯O interactions were observed in NBO calculations on exo-15, exo-17, and exo-20 transition states. However, the interaction was no stronger in the hydantoin and thiohydantoin transition states than for the oxazolone. Thus, while it may lead to some overall stabilization of the exo-transition states, it does not account for the higher selectivity observed with hydantoins and thiohydantoins
-
A referee noted the possibility for a C-H⋯O interaction between the methylene of cyclopentadiene and carbonyl oxygens in the exo-transition states. Weak C-H⋯O interactions were observed in NBO calculations on exo-15, exo-17, and exo-20 transition states. However, the interaction was no stronger in the hydantoin and thiohydantoin transition states than for the oxazolone. Thus, while it may lead to some overall stabilization of the exo-transition states, it does not account for the higher selectivity observed with hydantoins and thiohydantoins.
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68
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37549004562
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DFT calculations predict similar selectivity and reactivity for E-β-chloromethylene hydantoin and thiohydandtoin dienophiles, suggesting that our approach might be extended to access the chloride stereochemistry of 1b and the axinellamines.
-
DFT calculations predict similar selectivity and reactivity for E-β-chloromethylene hydantoin and thiohydandtoin dienophiles, suggesting that our approach might be extended to access the chloride stereochemistry of 1b and the axinellamines.
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