Highly diastereo- and enantioselective direct Barbas–List aldol reactions promoted by novel benzamidoethyl and benzamidopropyl prolinamides in water

Pedrosa, Rafaël; Andrés, José M.; Manzano, Rubén; Roman, Dávid; Téllez, Silvia

doi:10.1039/c0ob00688b

Cited by 41 publications

(14 citation statements)

References 76 publications

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“…Furthermore, this heterogeneous catalyst could be recovered by simple decantation and reused up to three times affording similar results. The use of benzoamidoethyl prolinamide (25 mol%) and acetic acid as cocatalyst (40 mol%) in the same reaction in water as solvent provided compound 54c in better results [173]. Several amides derived from proline and chiral amines have been tested in the aldol reaction (Table 3.7).…”

Section: Aldehydes As Electrophilesmentioning

confidence: 99%

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: Aldehydes As Electrophilesmentioning

confidence: 99%

Organocatalyzed Aldol Reactions

Guillena¹

2013

Modern Methods in Stereoselective Aldol Reactions

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“…synthesized benzamide‐functionalized prolinamide 68 from the achiral ethylene diamine and evaluated this organocatalyst in enantioselective aldol reaction of aldehyde and ketone in water. The catalyst afforded the aldol product in 90% yield with anti/syn (98/2) and 97% ee (Scheme ) . Excellent diastereoselectivity and enantioselectivity is determined by the stereocenter of the proline component of the catalyst.…”

Section: Prolinamide Catalysed Direct Asymmetric Aldol Reactionmentioning

confidence: 99%

“…The catalyst afforded the aldol product in 90% yield with anti/syn (98/2) and 97% ee (Scheme 36). [70] Excellent diastereoselectivity and enantioselectivity is determined by the stereocenter of the proline component of the catalyst. Because of non-bonding repulsion 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 between the R group of activated aldehydes and p-tolyl substituent of amide in the transition state model, III is more favorable than the IV.…”

Section: Prolinamide Catalysed Direct Asymmetric Aldol Reactionmentioning

confidence: 99%

Prolinamide‐Catalysed Asymmetric Organic Transformations

2019

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Proline was reported as an enantioselective organocatalyst for direct asymmetric aldol reaction in the early 1971 s by two independent groups of researchers and the reaction was called the Hajos‐Parrish‐Eder‐ Sauer Wiechert reaction. The breakthrough of enantioselective organocatalysis was demonstrated by List and co‐workers in 2000 for intermolecular aldol reaction between benzaldehydes and ketone using proline as a catalyst. After this report many researchers were applied the proline as a catalyst for other organic transformation. The proline has a carboxylic functional group which can easily convert to the amide and known as prolinamide. Prolinamides were found to be a better catalyst compared to proline in the most of cases. In this review article we are compiling the results of the prolinamides catalyzed asymmetric organic transformation with insight of the mechanism of catalysis.

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“…In spite of a variety of commercially available CSPs, most enantioseparations of aldols are reported on polysaccharide‐based selectors in which the sugar hydroxyls of the cellulose or amylose chiral backbone are derivatized with 3,5‐dimethylphenylcarbamate groups and specific compounds are better resolved on tris‐( S )‐α‐methylbenzylcarbamate amylose . Although optimal conditions for the analysis of a large number of chiral aldols have been developed in the context of the extensive research on asymmetric aldol reaction, a systematic study focused on the chromatographic features of this class of compounds on these CSPs is still missing.…”

Section: Introductionmentioning

confidence: 99%

Enantioseparation of aldols by high‐performance liquid chromatography on polysaccharide‐based chiral stationary phases that bear chlorinated substituents

Pedotti

Patti

2014

J of Separation Science

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Two families of aldols, obtained from the condensation of aromatic aldehydes with cyclohexanone or acetone (ten examples in each group), were analyzed by high-performance liquid chromatography in normal phase elution mode on three polysaccharide-based chiral stationary phases of the Lux series, namely, Lux Cellulose-2, Lux Cellulose-4 and Lux Amylose-2, which share the common feature of chlorinated substituents in the chiral selectors. Following simple optimization steps, the enantioseparation of all aldols derived from cyclohexanone was achieved and the highest values of separation factor (α, 1.32 < α < 2.20) and resolution (Rs , 4.5 < Rs <17.2) were observed on Lux Cellulose-2, with the only exception of the 4-nitro-substituted derivative that was better resolved on Lux Cellulose-4. On the contrary, Lux Amylose-2 was the best choice for aldols derived from acetone and only specific analytes in this group were resolved on the cellulose-based supports. A variable-temperature study of selected compounds allowed us to determine thermodynamic parameters of the enantioseparation process, which was enthalpy-controlled in all the cases except one.

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Highly diastereo- and enantioselective direct Barbas–List aldol reactions promoted by novel benzamidoethyl and benzamidopropyl prolinamides in water

Cited by 41 publications

References 76 publications

Organocatalyzed Aldol Reactions

Organocatalyzed Aldol Reactions

Prolinamide‐Catalysed Asymmetric Organic Transformations

Enantioseparation of aldols by high‐performance liquid chromatography on polysaccharide‐based chiral stationary phases that bear chlorinated substituents

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