Asymmetric synthesis of a 3,4-substituted pyrrolidine by l-proline catalyzed direct enolexo aldolization

Kumar, Indresh; Bhide, S.R.; Rode, C.V.

doi:10.1016/j.tetasy.2007.05.004

Cited by 17 publications

(6 citation statements)

References 33 publications

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“…In this case, a simple recrystallization led to an improvement on the diastereomeric and enantiomeric excesses, up to 99%. This type of process has been used in the high diastereo-and enantioselective asymmetric synthesis of polyhydroxylated 3,4-substituted pyrrolidines [27].…”

Section: Proline As Organocatalyst 157mentioning

confidence: 99%

“…The most plausible mechanism involves the formation of a nucleophilic enamine (27), through a deprotonation step from the zwitterionic iminium intermediate (24). The enhanced nucleophilicity of the enamine C=C bond together with the activation of carbonyl electrophile in the intermediate 28 by the carboxylic acid constitutes the basis of the new proposed mechanism, with many of the steps being equilibriums or reversible processes.…”

Section: Intramolecular Proposed Mechanismmentioning

confidence: 99%

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Organocatalyzed Aldol Reactions

Guillena¹

2013

Modern Methods in Stereoselective Aldol Reactions

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The use of catalytic enantioselective methods to perform an aldol reaction provides a direct entry for the synthesis of chiral compounds and is probably the most attractive way to achieve this goal with high control of the chemo-, regio-, diastereo-, and enantioselectivity. The application of biochemical methods based on enzyme aldolases or antibodies, which are discussed in other chapters, avoid the use of preformed enolates or their equivalents for enhancing the global atom efficiency of the process [1] for which the narrow substrate scope is a major drawback. The discovery of methodologies to carry out the enantioselective direct aldol reaction [2] has eluded the production of stoichiometric by-products increasing the substrate scope. This task could be accomplished by using small molecules as catalysts, such as metal complexes (which are covered along this book) and organic molecules, also known as organocatalysts [3]. The growth of this last research area and the direct aldol reaction are closely linked [4], with the report on the use of (S)-proline as catalyst for the intermolecular aldol [5] definitely being the push for the development of the organocatalytic methods as a competitive methodology for the synthesis of chiral compounds.In a strict sense, an organocatalyzed reaction is a process in which all the involved reagents and catalysis are purely organic compounds of low-molecular weight, excluding boron-and silicon-containing derivatives. However, in some cases, the presence of a silyl group only plays a steric role and therefore can also be considered as an organocatalyzed process. Also, if the organocatalyst involved in a reaction is immobilized in a polymer, a dendrimer, or even an inorganic material that serves only as a support to facilitate its recovery [6], it could still be considered as an organocatalyst, although those types of derivatives have been scarcely used in the natural product synthesis and therefore will be excluded from this chapter. Therefore, a comprehensive overview of the direct aldol reaction [7], emphasizing the reactivity, scope, selectivity, and limitations of the methodology and giving several examples of their application to the synthesis of biologically active compounds, is discussed in this chapter.

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Section: Proline As Organocatalyst 157mentioning

confidence: 99%

Section: Intramolecular Proposed Mechanismmentioning

confidence: 99%

Organocatalyzed Aldol Reactions

Guillena¹

2013

Modern Methods in Stereoselective Aldol Reactions

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“…Enantiopure glyceraldehyde is an interesting chiral building block which can be used as starting material for the synthesis of a variety of different fine chemicals, pharmaceuticals, and natural products (Areces et al, 2007;Bi and Aggarwal, 2008;Bull et al, 2007;Kumar et al, 2007). Therefore, we tried to transfer results regarding the cell-free system (Richter et al, 2009) to a whole-cell system (Fig.…”

Section: Application Of the Whole-cell Catalyst In The Kinetic Resolumentioning

confidence: 99%

Characterization of a whole‐cell catalyst co‐expressing glycerol dehydrogenase and glucose dehydrogenase and its application in the synthesis of L‐glyceraldehyde

Richter¹,

Neumann²,

Liese³

et al. 2010

Biotech & Bioengineering

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A whole-cell catalyst using Escherichia coli BL21(DE3) as a host, co-expressing glycerol dehydrogenase (GlyDH) from Gluconobacter oxydans and glucose dehydrogenase (GDH) from Bacillus subtilis for cofactor regeneration, has been successfully constructed and used for the reduction of aliphatic aldehydes, such as hexanal or glyceraldehyde to the corresponding alcohols. This catalyst was characterized in terms of growth conditions, temperature and pH dependency, and regarding the influence of external cofactor and permeabilization. In the case of external cofactor addition we found a 4.6-fold increase in reaction rate caused by the addition of 1 mM NADP(+). Due to the fact that pH and temperature are also factors which may affect the reaction rate, their effect on the whole-cell catalyst was studied as well. Comparative studies between the whole-cell catalyst and the cell-free system were investigated. Furthermore, the successful application of the whole-cell catalyst in repetitive batch conversions could be demonstrated in the present study. Since the GlyDH was recently characterized and successfully applied in the kinetic resolution of racemic glyceraldehyde, we were now able to transfer and establish the process to a whole-cell system, which facilitated the access to L-glyceraldehyde in high enantioselectivity at 54% conversion. All in all, the whole-cell catalyst shows several advantages over the cell-free system like a higher thermal, a similar operational stability and the ability to recycle the catalyst without any loss-of-activity. The results obtained making the described whole-cell catalyst an improved catalyst for a more efficient production of enantiopure L-glyceraldehyde.

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“…It is common that amino acids as proline or proline derivates are used as catalysts in intramolecular aldol reactions of dicarbonyl compounds. 10,11,14,17,[19][20][21][22][23][24] In the past years the mechanism of this reaction has been intensively studied by theoretical approaches. [25][26][27][28][29][30][31] Houk has proposed a mechanism for 6-enolendo aldolizations of diketones, [25][26][27][28][29] and on the basis of Houk's results, List proposed an empirical model for the 6-enolexo variant.…”

Section: Jocarticlementioning

confidence: 99%

Asymmetric Intramolecular Aldol Reactions of Substituted 1,7-Dicarbonylic Compounds. A Mechanistic Study

et al. 2010

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The diastereo- and enantioselectivity obtained experimentally by List on the proline-catalyzed intramolecular aldol reaction of substituted 1,7-dicarbonylic compounds was accurately predicted using density functional theory methods at the B3LYP/6-31++G** level. A polarizable continuum model was used to describe solvent effects. The theoretical data agree in good extension with List's experimental results, both in enantioselectivity and diastereoselectivity, and allow for the confirmation of our previous rationalization of the main factors contributing to the reaction selectivity. While the enantioselectivity results from an important electrostatic contact between the forming alkoxyde group and the proline moiety, the calculated diasteroselectivity results from several steric contacts that can be established between the different substituents and from their relative orientation in respect to the ring conformation. However, for dialdehydes that can originate two diastereomeric enamine intermediates, the proline attack and the immonium formation steps can also be of major importance in the rationalization of the final reaction selectivity, as is the case in two of the six studied systems. The obtained data allows for a full rationalization of the known experimental systems as well as for the extrapolation to new ones with variable substitution at the carbonylic chain.

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Asymmetric synthesis of a 3,4-substituted pyrrolidine by l-proline catalyzed direct enolexo aldolization

Cited by 17 publications

References 33 publications

Organocatalyzed Aldol Reactions

Organocatalyzed Aldol Reactions

Characterization of a whole‐cell catalyst co‐expressing glycerol dehydrogenase and glucose dehydrogenase and its application in the synthesis of L‐glyceraldehyde

Asymmetric Intramolecular Aldol Reactions of Substituted 1,7-Dicarbonylic Compounds. A Mechanistic Study

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