Simple and practical direct asymmetric aldol reaction of hydroxyacetone catalyzed by 9-amino Cinchona alkaloid tartrates

Czarnecki, Paweł; Plutecka, Agnieszka; Gawroński, Jacek; Kacprzak, Karol

doi:10.1039/c1gc15064b

Cited by 20 publications

(4 citation statements)

References 59 publications

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“…Better results were obtained using cinchonine-derived amine (355, 10 mol%) combined with TFA (15 mol%) in the reaction between cyclic ketones and aromatic aldehydes (19-99% yield, 0-80% de, and 56-99% ee) [419]. Its epimeric compound 356 at the carbon atom bearing the amine group (2 mol%) as its tartrate salt was used in the reaction of hydroxyacetone (58a) and aromatic aldehydes, mainly providing syn-59 with up to 87% enantioselectivity [420]. The use of only 3 mol% compound 387 in brine at 5 • C as catalyst permitted the reaction between cyclohexanone (52c) and aromatic aldehydes, providing the aldol product in good yields and diastereoselectivies (65-93% and 80-98% de) but with moderate enantioselectivities (45-92% ee) [421].…”

Section: Ketones As Source Of Nucleophilementioning

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: Ketones As Source Of Nucleophilementioning

confidence: 99%

Organocatalyzed Aldol Reactions

Guillena¹

2013

Modern Methods in Stereoselective Aldol Reactions

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“…A proposed catalytic cycle and transition state model [27] Notably, this reaction was successfully conducted on a 2-mmol scale (Scheme 2), with product 4j obtained in 86% yield with 95% ee and 89:11 dr. The relative and absolute configurations of 4j (2S,3R) were determined by X-ray crystallography (see the Supplementary Materials) [26].…”

Section: Plausible Reaction Mechanism and Transition Statesmentioning

confidence: 99%

Organocatalytic Asymmetric Aldol Reaction of Arylglyoxals and Hydroxyacetone: Enantioselective Synthesis of 2,3-Dihydroxy-1,4-diones

Zhou

Zhang

et al. 2020

Molecules

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“…In this communication, a novel family of bioinspired organocatalysts is presented [ 10 ] ( Figure 1 C) based on the hydrogen bonding features of the acylguanidinium group and its application in the asymmetric aldol reaction of hydroxyacetone, a typical substrate for class I aldolases and thoroughly studied in bioinspired catalysis and organocatalysis. Selected examples are given in references [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Amino Acylguanidines as Bioinspired Catalysts for the Asymmetric Aldol Reaction

Jimeno

2021

Molecules

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The binding and stabilizing effect of arginine residues in certain aldolases served as inspiring source for the development of a family of amino acylguanidine organocatalysts. Screening and optimization led to identify the threonine derivative as the most suitable catalyst for the asymmetric aldol addition of hydroxyacetone, affording the syn diastereomer in high ee. In contrast, the proline derivative yielded the anti diasteromer. MMFF models suggest the presence of an extensive hydrogen bonding network between the acylguanidinium group and the reaction intermediates.

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Simple and practical direct asymmetric aldol reaction of hydroxyacetone catalyzed by 9-amino Cinchona alkaloid tartrates

Cited by 20 publications

References 59 publications

Organocatalyzed Aldol Reactions

Organocatalyzed Aldol Reactions

Organocatalytic Asymmetric Aldol Reaction of Arylglyoxals and Hydroxyacetone: Enantioselective Synthesis of 2,3-Dihydroxy-1,4-diones

Amino Acylguanidines as Bioinspired Catalysts for the Asymmetric Aldol Reaction

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