Pyrrolidine—Thiourea as a Bifunctional Organocatalyst: Highly Enantioselective Michael Addition of Cyclohexanone to Nitroolefins.

Cao, Chun‐Li; Ye, Mengchun; Sun, Xiu‐Li; Tang, Yong

doi:10.1002/chin.200646032

Cited by 263 publications

(22 citation statements)

References 12 publications

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“…[15,16] According to the philosophy of Sheldon, [17] who states "the best solvent is no solvent", one strategy for the development of more environmentally friendly protocols involves solvent-free reactions. In some cases, this has been achieved using an excess of a liquid reagent, [18][19][20][21] in others it has been possible to use almost equimolar amounts of reagents under solvent-free conditions to achieve good results. [22,23] The Michael addition is considered as one of the most powerful tools for the formation of C-C bonds.…”

Section: Introductionmentioning

confidence: 99%

Use of (R)-Mandelic Acid as Chiral Co-Catalyst in the Michael Addition Reaction Organocatalyzed by (1S,4S)-2-Tosyl-2,5-diazabicyclo[2.2.1]heptane under Solvent-Free Conditions

Avila‐Ortiz

López-Ortíz

Vega‐Peñaloza

et al. 2015

Asymmetric Catalysis

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This article describes a study on the Michael addition reaction of cyclohexanone to nitroolefins catalyzed by the chiral secondary amine (1S,4S)-2-tosyl-2,5-diazabicyclo[2.2.1]heptane. Reactions were carried out under solvent-free conditions to make them more environmentally friendly. Initially, the observed diastereoand enantioselectivities were moderate to good, but were significantly improved by lowering the reaction temperature. Furthermore, a variety of chiral acids were also tested as co-catalysts in both of their enantiomeric forms, which revealed that (R)-mandelic acid affords excellent results in terms of yield and stereoselectivity. Monitoring the reaction by MS-TOF allowed for the detection of key reaction intermediates, and a reasonable reaction mechanism in which both catalysts are involved is proposed.

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Section: Introductionmentioning

confidence: 99%

Use of (R)-Mandelic Acid as Chiral Co-Catalyst in the Michael Addition Reaction Organocatalyzed by (1S,4S)-2-Tosyl-2,5-diazabicyclo[2.2.1]heptane under Solvent-Free Conditions

Avila‐Ortiz

López-Ortíz

Vega‐Peñaloza

et al. 2015

Asymmetric Catalysis

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“…For selected reviews see references, [1][2][3][4] for selected stereoselective transformations/organocatalysts see references. [8][9][10][11][12][13][14][17][18][19][20][21][22] Recently, a class of chiral bifunctional thiourea organocatalysts based on terpenes has been reviewed. [8][9][10][11][12][13][14][17][18][19][20][21][22] Recently, a class of chiral bifunctional thiourea organocatalysts based on terpenes has been reviewed.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel Camphor‐Derived Bifunctional Thiourea Organocatalysts

et al. 2014

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Synthesis and catalyst performance of 2,3- (types and ) and 2,8-disubstituted (type ) thiourea bifunctional organocatalysts was attempted. The synthesis of catalyst of type has, so far, not been realized, while catalysts of type , i.e., the 2,3-exo- and the 2-endo-3-exo-thiourea catalysts, were prepared in six steps starting from (+)-camphor. The catalysts of type were prepared from (+)-camphor in eight steps. All the potential catalysts as well as most of the intermediate products were carefully structurally characterized. The thiourea bifunctional organocatalysts were tested in a model reaction of Michael addition of dimethyl malonate to trans-β-nitrostyrene.

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“…The preferred chiral secondary amines are substituted pyrrolidines with a myriad of substituents in the 2‐position. A by no means complete or chronological collection is presented in Scheme for illustration purposes.…”

Section: Introductionmentioning

confidence: 99%

“…The regioselectivity has been discussed in terms of higher stability of the corresponding enamine with a trisubstituted double bond ( Scheme ). Besides the explicit discussions of these remarkable phenomena, a difference in the stability of the enamines is often assumed implicitly when suggesting transition state models in which the enamines adopt an s‐ trans or s‐ cis conformation …”

Section: Introductionmentioning

confidence: 99%

“…Schematic trajectories of enamine‐nitroolefin coupling with anti ( A , B ) and syn arrangements ( C ) of a substituent in 2‐position of the pyrrolidine ring . Interactions, such as in C , of a syn substituent with the nitro group have been invoked in many mechanistic proposals, disregarding the fact that a nitro group is a poor H‐bond acceptor . Thus, depending on the solvent, a functional group on the pyrrolidine ring may be considered as just another large substituent, as suggested in B′ for a proline derivative.…”

Section: Introductionmentioning

confidence: 99%

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Rigorous Conformational Analysis of Pyrrolidine Enamines with Relevance to Organocatalysis

Husch

Seebàch

Beck

et al. 2017

Helvetica Chimica Acta

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It has been suggested that the origin of regio-and stereoselectivity in Michael additions of pyrrolidine enamines is achieved by thermodynamic rather than kinetic control through distinct conformational preferences of the enamines. We assess this proposal by elaboration of a computational protocol that warrants sufficient accuracy. The small energy differences between the conformers necessitate a high accuracy of the electronic structure method which, in addition, must allow for computationally feasible calculations of a large number of conformers. Our protocol is based on density functional theory which we validated against explicitly correlated coupled cluster theory. The results are in agreement with the available experimental data, but illustrate that conformational preferences determined for one enamine are not readily transferable to other types of enamines. We found that an appropriate conformational sampling is inevitable to arrive at meaningful conclusions. Most prominently, s-cis and strans conformers are similarly stable for aldehyde-and ketone-derived enamines. The regio-and stereoselectivity in Michael additions of pyrrolidine-derived enamines can not be explained by pronounced stability differences of the enamine isomers and conformers in general, disproving the thermodynamic-control hypothesis. The elucidation of the origin of regio-and stereoselectivity requires further theoretical investigations of the elementary steps of Michael additions.

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Pyrrolidine—Thiourea as a Bifunctional Organocatalyst: Highly Enantioselective Michael Addition of Cyclohexanone to Nitroolefins.

Abstract: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Cited by 263 publications

References 12 publications

Use of (R)-Mandelic Acid as Chiral Co-Catalyst in the Michael Addition Reaction Organocatalyzed by (1S,4S)-2-Tosyl-2,5-diazabicyclo[2.2.1]heptane under Solvent-Free Conditions

Use of (R)-Mandelic Acid as Chiral Co-Catalyst in the Michael Addition Reaction Organocatalyzed by (1S,4S)-2-Tosyl-2,5-diazabicyclo[2.2.1]heptane under Solvent-Free Conditions

Synthesis of Novel Camphor‐Derived Bifunctional Thiourea Organocatalysts

Rigorous Conformational Analysis of Pyrrolidine Enamines with Relevance to Organocatalysis

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