Dipeptide-catalyzed direct asymmetric aldol reactions in the presence of water

Meng, Lei; Shi, Lei; Gong, L.; Chen, Shilv; Fang, Wei‐Hai; Zhang, Ge; Cheng, Tanyu; Li, Runtao

doi:10.1016/j.tet.2007.05.077

Cited by 106 publications

(40 citation statements)

References 49 publications

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“…However, in the reaction between cyclohexanone and aromatic aldehydes, mainly the anti-54 aldol product was obtained in good results (62-94%, 35-96% de, and 55-95% ee) applying similar reaction conditions [233]. Dipeptide H-Pro-Trp-OH (169d) in the presence of NMM and SDS in water catalyzed the aldol reaction between cyclic ketones and several aromatic aldehydes yielding the expected products 54 in good yields (67-94%), diastereo-(50-99% de), and enantioselectivities (72-95% ee), with lower enantioselectivity being encountered using acetone as nucleophile (Table 3.12, entry 4) [234]. In this case, the corresponding methyl ester of the dipeptide (169d, 3 mol%) was also used in ball-mill solvent-free reaction conditions in the presence of water (1.1 equiv) and benzoic acid (5 mol%) in the reaction between cyclic ketones and several aromatic aldehydes providing anti-aldols 54 in good results (64-90%, 84-92% de, and 55-98% ee) [235].…”

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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“…[8] Since 2006, several papers appeared on this topic. Simple tryptophan, [9] or other aromatic amino acids, [10] and dipeptides, in aqueous media [11] or in the presence of water and additives [12] were used. Apart from these molecules, the asymmetric direct aldol reaction in water has been carried out with molecules of general formulae II, III and IV (Figure 3).…”

Section: Introductionmentioning

confidence: 99%

New Simple Hydrophobic Proline Derivatives as Highly Active and Stereoselective Catalysts for the Direct Asymmetric Aldol Reaction in Aqueous Medium

et al. 2008

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New 4-substituted acyloxyproline derivatives with different hydrophobic properties of the acyl group were easily synthesized and used as catalysts in the direct asymmetric aldol reaction between cyclic ketones (cyclohexanone and cyclopentanone) and several substituted benzaldehydes. Reactions were carried out using water, this being the best reaction medium examined. Screening of these catalysts showed that compounds bearing the most hydrophobic acyl chains [4-phenylbutanoate and 4-(pyren-1-yl)butanoate] provided better results. The latter catalysts were successfully used in only 2 mol% at room temperature without additives to give aldol products in excellent stereoselectivities. These results demonstrate that derivatization of the proline moiety with the proper simple hydrophobic substituent in the 4-position can furnish highly active and stereoselective catalysts without the need of additional chiral backbones in the molecule. Finally, an explanation of the observed stereoselectivities in the presence of water is provided.

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“…Figure 2 depicts grosso modo the development of ligands with an efficient organocatalytic activity, from simple and affordable chiral compounds such as amino acids, up to molecules with greater complexity and versatility. [58][59][60][61][62][63][64][65][66][67][68][69][70][71] Given the great diversity of reactions in which it is possible to employ (R)-or (S)-proline and its derivatives as organocatalysts, it is worthy to mention that relatively few methods of activation were initially identified. 10,71,72 For example, the stereoinduction observed in reactions listed in Figure 3 is ruled by a simplified rationalization of the mechanistic principle of catalysis via enamine.…”

Section: Synopsis Of the Development Of Organocatalysts And Their Appmentioning

confidence: 99%

Determination of Enantioselectivities by Means of Chiral Stationary Phase HPLC in Order to Identify Effective Proline-Derived Organocatalysts

Vargas-Caporali¹,

Juaristi²

2017

J. Braz. Chem. Soc.

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The pyrrolidine fragment is a privileged scaffold within chiral ligands employed in coordination complexes exhibiting catalytic activity in asymmetric reactions and, more recently, as enantioselective organocatalysts per se. Likewise, the employment of (S)-proline as starting material constitutes the most direct form to synthesize those chiral derivatives. Afterwards, a preliminary evaluation of the catalytic performance of proline-derived compounds consists of screening many prochiral substrates in well standardized model reactions such as Michael additions and Mannich reactions, with the aim of identifying "broad spectrum" catalysts for more complex synthetic applications. Therefore, a central part of this process involves the fast and direct measurement of enantioselectivities of optically active adducts. The growing development of chiral stationary phases and thus, the wide commercial availability of chiral columns have consolidated high performance liquid chromatography (HPLC) as the preferred technique to identify the most effective catalysts.

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Dipeptide-catalyzed direct asymmetric aldol reactions in the presence of water

Cited by 106 publications

References 49 publications

Organocatalyzed Aldol Reactions

Organocatalyzed Aldol Reactions

New Simple Hydrophobic Proline Derivatives as Highly Active and Stereoselective Catalysts for the Direct Asymmetric Aldol Reaction in Aqueous Medium

Determination of Enantioselectivities by Means of Chiral Stationary Phase HPLC in Order to Identify Effective Proline-Derived Organocatalysts

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