Diels-Alder reactions in aqueous media

Garner, Philip

doi:10.1007/978-94-011-4950-1_1

Cited by 18 publications

(9 citation statements)

References 74 publications

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“…endo-1-tert-Butoxycarbonyl-3,3-dicyano-1,2,3,10btetrahydropyrollo[2,1-a]phthalazine and exo-1-tert-Butoxycarbonyl isomer and endo-2-tert-Butoxycarbonyl-3,3-dicyano-1,2,3,10b-tetrahydropyrrolo[2,1-a]phthalazine (11). A suspension of the compound 1 (0.30 g, 1.54 mmol) in acetonitrile (20 mL) was treated with t-butyl acrylate (1.12 mL, 7.7 mmol) stirred at ambient temperature for 24 h, giving a pale yellow solution.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Water and Organic Synthesis: A Focus on the In-Water and On-Water Border. Reversal of the In-Water Breslow Hydrophobic Enhancement of the Normal endo-Effect on Crossing to On-Water Conditions for Huisgen Cycloadditions with Increasingly Insoluble Organic Liquid and Solid 2π-Dipolarophiles

et al. 2013

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Measurements of the endo/exo product ratios for Huisgen cycloadditions with a series of vinyl ketones, alkyl acrylates, and substituted styrenes as dipolarophiles with phthalazinium and pyridazinium dicyanomethanide 1,3-dipoles in acetonitrile and water show that as the reactions change from in-water (large hydrophobic enhancement of endo-products) to on-water, the hydrophobic enhancement of the endo-products is reduced and partially reversed (relative to acetonitrile). An expected increase of the endo-effect with increasing hydrophobic character of the dipolarophile is overcome by decreasing water solubility causing changeover to on-water conditions. On-water reactions do not show increased cycloaddition endo-effects (relative to organic solvents) as do in-water reactions.

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Section: ■ Experimental Sectionmentioning

confidence: 99%

Water and Organic Synthesis: A Focus on the In-Water and On-Water Border. Reversal of the In-Water Breslow Hydrophobic Enhancement of the Normal endo-Effect on Crossing to On-Water Conditions for Huisgen Cycloadditions with Increasingly Insoluble Organic Liquid and Solid 2π-Dipolarophiles

et al. 2013

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“…The Diels−Alder reaction is one of the most important and widely used carbon−carbon bond-forming processes in organic chemistry. − Due to the broad scope and proven usefulness of the Diels−Alder reaction, there have been extensive efforts to control the rate and regio, endo/exo , and diastereofacial selectivities by using the aqueous phase. − Generally, pericyclic reactions are regarded as concerted and nearly synchronous reactions , that have insignificant charge build-up in their corresponding transition structures . As a result, it is commonly thought that many pericyclic reaction rates and stereoselectivities remain unaffected by solvent. − Despite the assumption of a relatively static charge distribution, it is now well-established that several reactions from different pericyclic classifications, such as the Diels−Alder reaction, − hetero-Diels−Alder reaction, − 1,3-dipolar cycloaddition, − Claisen rearrangement, − and aldol 44 and benzoin condensations, − are strongly accelerated in aqueous medium. In particular, the rates of Diels−Alder reactions have been accelerated by factors up to 1.3 × 10 4 in aqueous solution as compared to organic solvents. , …”

Section: Introductionmentioning

confidence: 99%

Density Functional Theory Study of Aqueous-Phase Rate Acceleration and Endo/Exo Selectivity of the Butadiene and Acrolein Diels−Alder Reaction

and

Evanseck

2000

J. Am. Chem. Soc.

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The four stereospecific transition structures of the butadiene and acrolein Diels-Alder reaction have been studied using the Becke three-parameter density functional theory with the 6-31G(d) basis set. The effect of solvent on the activation energies and endo/exo selectivity has been approximated by the polarizable continuum model (PCM); explicit definition of one, two, and three waters; and the combined strategy of the discrete-continuum model. The full aqueous acceleration and enhanced endo/exo selectivity observed by experiment is computed only when solvation forces are approximated by the discrete-continuum model. Consistent with previous ideas, two explicit waters are used to satisfy localized hydrogen bonding of acrolein and induce a charge polarization of the endo s-cis transition structure. Smaller enforced hydrophobic interactions result. Significant bulk-phase effects beyond hydrogen bonding and enforced hydrophobic interactions are computed for the first time. The gas-phase activation energy is lowered to 11.5 kcal/mol, in excellent agreement with known experimental activation energies of similar Diels-Alder reactions in mixed methanol and water solutions. The computed endo preference is enhanced to 2.4 kcal/mol in aqueous solution, in agreement with experiment. Approximately 50% of the rate acceleration and endo/exo selectivity is attributed to hydrogen bonding, and the remainder to bulk-phase effects, which includes enforced hydrophobic interactions and antihydrophobic cosolvent effects. The local and bulk influence of solvent on the energetics, endo/exo selectivity, and transition structure asynchronicity is discussed and analyzed for this particular pericyclic reaction that has a well-known and strong solvent dependency. The catalytic and endo/exo selectivity results are consistent with the hypothesis of maximum accumulation of unsaturation and support the importance of antihydrophobic cosolvents in stabilizing hydrophobic regions of transition structures.

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“…Considerable effort has been devoted to the discovery of new catalysts for Diels−Alder cycloadditions, with the primary objective being to enhance reactivity or control selectivity …”

Section: Introductionmentioning

confidence: 99%

Characteristics of an RNA Diels−Alderase Active Site

Tarasow

et al. 1999

J. Am. Chem. Soc.

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The active site components and substrate specificity of an RNA Diels−Alderase (DA22) were investigated. Diels−Alderase activity was found to be highly dependent on a unique 5-position pyridyl modified uridine. Even closely related pyridyl modifications failed to yield active catalysts. Substrate specificity of this Diels−Alderase was remarkable. Experiments with alternative diene and dienophile substrates showed the active site of the Diels−Alderase to be highly discriminating, even against molecules of similar reactivity and structure. Inhibition studies with a series of product analogues established that the RNA recognizes functional components in and around the reaction center of both the diene and the dienophile. Taken together, these results suggest that DA22 can fold into a structure that produces an intricate metal/ligand dependent active site capable of highly specific molecular recognition.

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Diels-Alder reactions in aqueous media

Cited by 18 publications

References 74 publications

Water and Organic Synthesis: A Focus on the In-Water and On-Water Border. Reversal of the In-Water Breslow Hydrophobic Enhancement of the Normal endo-Effect on Crossing to On-Water Conditions for Huisgen Cycloadditions with Increasingly Insoluble Organic Liquid and Solid 2π-Dipolarophiles

Water and Organic Synthesis: A Focus on the In-Water and On-Water Border. Reversal of the In-Water Breslow Hydrophobic Enhancement of the Normal endo-Effect on Crossing to On-Water Conditions for Huisgen Cycloadditions with Increasingly Insoluble Organic Liquid and Solid 2π-Dipolarophiles

Density Functional Theory Study of Aqueous-Phase Rate Acceleration and Endo/Exo Selectivity of the Butadiene and Acrolein Diels−Alder Reaction

Characteristics of an RNA Diels−Alderase Active Site

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