<i>exo</i>-
and Enantioselective Diels-Alder Reactions: Pyrazolidinone
Auxiliaries as a Means to Enhanced <i>exo</i> Selectivity

Sibi, Mukund P.; Nie, Xiaolu; Shackleford, Jessica P.; Stanley, Levi M.; Bouret, Frances

doi:10.1055/s-0028-1083438

Cited by 18 publications

(7 citation statements)

References 2 publications

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“…(1)]. Alternatively, catalyst‐induced anomalous exo ‐selective Diels–Alder reactions that contravene the endo rule have been performed by Yamamoto and co‐workers3 in a non‐asymmetric manner, and later by Maruoka and co‐workers,4 Sibi et al,5 and Hayashi et al6 in an asymmetric manner. In contrast, enantiomerically enriched endo ‐ 3 b with a quaternary carbon center can not be generated by the epimerization of exo ‐ 3 b or by other known synthetic methods [Eq.…”

Section: Methodsmentioning

confidence: 99%

NMR (Pro)chiral Discrimination Using Polysaccharide Gels

Naumann

Kuchel

2009

Chemistry A European J

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Residual dipolar couplings (RDCs) are valuable for structure determination by solution-state NMR spectroscopy; this useful attribute has led to the development of several classes of alignment media such as liquid crystals, bicelle and phage suspensions, and compressed polyacrylamide gels.[1] Chiral media such as stretched gelatin and collagen have also been shown recently to resolve enantiomers by quasi diastereomeric complexation.[2] The degree of alignment in the magnetic field that guest molecules inside these media experience is generally a function of the concentration of the latter down to a minimum anisotropic concentration for that particular medium. However it would be very advantageous if one could reversibly adjust the resulting RDCs within a wide range without having to change the sample because of overlapping and unresolved spectral resonances. In addition it would be even better to be able to switch the sign of the dipolar coupling constant D when needed. Recently we described a simple device that achieves this by using a gel of gelatin as the chiral alignment medium. [3,4] The method is based on the gel containing polar guest molecules in an elastic silicone rubber tube that allows the rapid and reversible adjustment of the degree of nuclear alignment inside the NMR samples (starting from zero alignment) by merely stretching the rubber tube. [4,5] Stretched samples can be quickly and reversibly converted into compressed ones by melting the stretched gel by heating it at 37 8C, letting the gel reset by cooling, and then (partially) releasing the now isotropic sample; this compresses the gel and changes the sign of D. Although gelatin has been an extremely versatile alignment medium, there are drawbacks to its use: the relatively high protein concentration needed to resolve mixtures may limit its use for structure determination of proteins, and the need to retain samples below 20 8C does not allow kinetic studies at physiological temperatures.Here, we describe two new chiral anisotropic gels that can be reversibly adjusted just like gelatin, but need much lower gel concentrations, and can be used at 37 8C. Some unanticipated properties of these gels (see below) provide new opportunities in studies of (pro)chiral molecular structures. These gels are commercially available polysaccharides prepared from seaweed: i-and k-carrageenan. As solutes prochiral glycine, alanine enantiomers, and prochiral [D 6 ]DMSO were used.The i-and k-carrageenan gels were prepared in concentrations between 3-10 % (w/v). Both gels were very sensitive to the concentration of NaCl, and generally became more rigid and brittle than identical gels prepared without added NaCl. i-Carrageenan formed the more elastic gel. Gelation occurred upon heating to 90 8C for several minutes, but we were also able to prepare i gels by restricting heating to 42 8C; this is a useful property if guest molecules, such as peptides and proteins, which readily denature in temperatures over 50 8C, are to be included in the sample. The guest molecules c...

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Section: Methodsmentioning

confidence: 99%

NMR (Pro)chiral Discrimination Using Polysaccharide Gels

Naumann

Kuchel

2009

Chemistry A European J

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“…(1)]. Alternatively, catalystinduced anomalous exo-selective Diels-Alder reactions that contravene the endo rule have been performed by Yamamoto and co-workers [3] in a non-asymmetric manner, and later by Maruoka and co-workers, [4] Sibi et al, [5] and Hayashi et al [6] in an asymmetric manner. In contrast, enantiomerically enriched endo-3 b with a quaternary carbon center can not be generated by the epimerization of exo-3 b or by other known synthetic methods [Eq.…”

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confidence: 97%

Enantioselective Diels–Alder Reactions with Anomalous endo/exo Selectivities Using Conformationally Flexible Chiral Supramolecular Catalysts

et al. 2011

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On the basis of Woodward-Hoffmann frontier molecular orbital interactions and steric interactions between dienes and dienophiles during the formation of [2+4] pericyclic transition states, endo/exo selectivity in the Diels-Alder reaction strongly depends on the substrates.[1] Therefore, it is quite difficult to control both enantioselectivity [2] and anomalous endo/exo selectivity by conventional chiral catalysts, which can discriminate only the enantiofaces of the dienophiles. For example, in the reaction between cyclopentadiene (1) and acrolein (2 a), an endo preference is observed with regard to second-order orbital interactions without significant steric interactions [Eq. (1)]. In sharp contrast, in the reaction between 1 and an a-substituted acrolein (R ¼ 6 H), such as methacrolein (2 b), an exo preference is observed with regard to steric interactions between the methylene moiety of 1 and the substituent R at the a position of the dienophile [Eq. (2)]. Therefore, enantiomerically enriched endo-3 a and exo-3 b have been synthesized by using many conventional chiral catalysts.[2] Moreover, thermodynamically more stable and enantiomerically enriched exo-3 a can be generated by the epimerization of endo-3 a [Eq. (1)]. Alternatively, catalystinduced anomalous exo-selective Diels-Alder reactions that contravene the endo rule have been performed by Yamamoto and co-workers [3] in a non-asymmetric manner, and later by Maruoka and co-workers, [4] Sibi et al., [5] and Hayashi et al. [6] in an asymmetric manner. In contrast, enantiomerically enriched endo-3 b with a quaternary carbon center can not be generated by the epimerization of exo-3 b or by other known synthetic methods [Eq. (2)]. To the best of our knowledge, no examples of catalyst-induced anomalous endo-selective enantioselective Diels-Alder reactions with a-substituted acroleins have been reported to date. To address this major yet unexplored subject, catalysts must discriminate chiral transition-state structures by precisely recognizing the re or si face of dienophiles, and the endo or exo approach of dienes, thus, the rational design of conformationally flexible chiral supramolecular catalysts, such as enzymes, is necessary. [7] As such, conformationally rigid metal-organic frameworks (MOFs) are not suitable as artificial enzymes because they have few induced-fit properties to adapt dynamics in transition states. [8] A chiral supramolecular catalyst (4 a) was readily prepared in situ from three components, which included 10 mol % of chiral (R)-3,3'-bis(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphorinan-2-yl)-BINOL (5 a; BINOL = 1,1'-bi(2-naphthol)), [9] 10 mol % of 3,5-bis(trifluoromethyl)phenylboronic acid (6 a), and 20 mol % of tris(pentafluorophenyl)borane (7), by taking advantage of the typical preparation of boron BINOLates [10] (Scheme 1). Intermolecular acid-base coordinate bonds in the two P=O···B(C 6 F 5 ) 3 moieties [11] are critical for the design of conformationally flexible complex 4 a; compound 7 acts as a bulky functional group to form a ch...

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“…[16] Surprisingly, the product displays an exo configuration in contrast to the previous endo-favored stereoselectivity of 3-olefinic oxindoles. [6] Although an exo-selective Diels-Alder reaction [19] of nitroalkenes with Danishefsky's diene was reported to be based on electrostatic repulsion between the nitro group and the silyloxy group of the diene, [20] the O-trimethylsilyl (OTMS) ether moiety of catalyst 1 a would not account for the exo selectivity in a similar way in the present study. As shown in Scheme 4, catalysts 1 e and 1 f delivered the same exo/endo ratios as that obtained with OTMS ether 1 a in the Diels-Alder reaction of 2,4-dienal 2 a and b-nitrostyrene 3 a, though the enantioselectivity was decreased.…”

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confidence: 44%

exo‐Selective Asymmetric Diels–Alder Reaction of 2,4‐Dienals and Nitroalkenes by Trienamine Catalysis

et al. 2011

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The asymmetric Diels-Alder reaction continues to generate research interest in organic chemistry because it provides one of the most powerful protocols to prepare six-membered carbo-or heterocycles with multiple chiral centers. The asymmetric Diels-Alder reaction is dominated by the activation of the LUMO of electron-poor dienophiles with chiral metal complexes [1] or organic molecules. [2] However, over the past decade, an alternative strategy has emerged in which the asymmetric Diels-Alder reaction can be promoted and controlled by raising the energy of the HOMO of the dienophile (inverse electron demand) or the diene (normal electron demand) through enamine [3] or dienamine catalysis. [4,5] Very recently, our research group and Jørgensen and co-workers [6] further expanded the synthetic potential of such an activation mode. It was discovered that a trienamine intermediate, which was generated in situ from 2,4-hexadienal and a chiral secondary amine, could serve as a diene in a normal-electron-demand Diels-Alder reaction with electrondeficient dienophiles, such as 3-olefinic oxindoles. The reaction exhibited exclusive regioselectivity and afforded the endo products in excellent ee and d.r. values [Eq. (1), Boc = tert-butyloxycarbonyl]. [6] Unfortunately, we subsequently found that the reaction is limited to highly activated dienophiles, such as alkylidenecyanoacetates. Although nitroalkenes typically demonstrate good dienophilicity in numerous Diels-Alder reactions, [7] the cycloaddition of 2,4-hexadienal and b-nitrostyrene did not proceed even at higher temperature (80 8C). [8] Although nitro-containing materials have great synthetic versatility in organic chemistry, there is still scarce precedence for catalytic stereoselective Diels-Alder reactions of nitroalkenes [9,10] in comparison with the wealth of asymmetric Michael addition reactions. [11] As a result, the development of such an asymmetric Diels-Alder reaction would be highly desirable. We envisioned that the electron-donating effect of appropriate alkyl substituents could further raise the HOMO level of the trienamine intermediate (Scheme 1), [12] such that the reaction barriers of the desired cycloaddition might be overcome.

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exo- and Enantioselective Diels-Alder Reactions: Pyrazolidinone Auxiliaries as a Means to Enhanced exo Selectivity

Cited by 18 publications

References 2 publications

NMR (Pro)chiral Discrimination Using Polysaccharide Gels

NMR (Pro)chiral Discrimination Using Polysaccharide Gels

Enantioselective Diels–Alder Reactions with Anomalous endo/exo Selectivities Using Conformationally Flexible Chiral Supramolecular Catalysts

exo‐Selective Asymmetric Diels–Alder Reaction of 2,4‐Dienals and Nitroalkenes by Trienamine Catalysis

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