Brønsted Acid Catalyzed Asymmetric Aldol Reaction: A Complementary Approach to Enamine Catalysis

Pousse, Guillaume; Cavelier, Fabien Le; Humphreys, Luke; Rouden, Jacques; Blanchet, Jérôme

doi:10.1021/ol101176j

Cited by 97 publications

(54 citation statements)

References 35 publications

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“…The acidic nature of Bronsted acidic ionic liquids as catalysts has been exploited for many organic transformations like Pechmann reaction, Koch carbonylation, asymmetric Aldol condensation, Aza-Michael reaction, Beckmann rearrangement, synthesis of chalcones, oxidation reactions and Prin's reaction, synthesis of furfural, biodiesel, Hantzsch reaction, and Mannich reaction to mention a few [78][79][80][81][82][83][84][85][86][87][88][89].…”

Section: As Acid Catalystsmentioning

confidence: 99%

Ionic Liquids: Synthesis and Applications in Catalysis

Rajni

2014

Advances in Chemistry

209

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Ionic liquids have emerged as an environmentally friendly alternative to the volatile organic solvents. Being designer solvents, they can be modulated to suit the reaction conditions, therefore earning the name "task specific ionic liquids. " Though primarily used as solvents, they are now finding applications in various fields like catalysis, electrochemistry, spectroscopy, and material science to mention a few. The present review is aimed at exploring the applications of ionic liquids in catalysis as acid, base, and organocatalysts and as soluble supports for catalysts.

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Section: As Acid Catalystsmentioning

confidence: 99%

Ionic Liquids: Synthesis and Applications in Catalysis

Rajni

2014

Advances in Chemistry

209

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“…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]. Not only chiral amines but also Brønsted acid derivative (358, 5 mol%; Scheme 3.73) catalyzed the aldol reaction between cyclohexanone, or other ketones, and ethyl glyoxylate (217), yielding mainly the syn-218 configurated products, where this relative stereoselectivity was opposite to that achieved when using proline derivatives (Scheme 3.50) [422].…”

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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“…19,[23][24][25][26][27][28][29][30][31] Especially, only limited work was done on the catalytic direct asymmetric aldol reactions of cyclohexanone with aldehydes that afford syn-products. [32][33][34] Herein, we report diastereoselectivity control in the asymmetric aldol reaction of cycloketones with aldehydes, with moderate to good enantioselectivity. Chiral primary amine compounds had been discovered to be suitable catalysts for the asymmetric aldol reaction.…”

mentioning

confidence: 98%

Acid controlled diastereoselectivity in asymmetric aldol reaction of cycloketones with aldehydes using enamine-based organocatalysts

et al. 2011

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The example of syn-aldol reaction of cyclohexanone to aldehyde was demonstrated based on chiral diamine organocatalysts and it was realized either by increasing the molecular size of acid additives or by introducing a hydrogen-bond donor into acid additives.The aldol reaction is one of the most efficient strategies for construction of various C-C bonds. [1][2][3][4][5][6][7][8][9][10][11][12] Since the pioneering works of the proline-catalyzed asymmetric direct aldol reaction by List, Barbas and co-workers, tremendous progress has been made for organo-catalyzed asymmetric aldol reactions. 13,14 Asymmetric aldol reactions of cycloketones with aldehydes provide an attractive strategy for the construction of b-hydroxy cycloketones which are important synthons for biological active molecules. 15 Highly enantioselective and diastereoselective reactions generating chiral compounds with two stereocenters in one step are valuable for asymmetric synthesis. [16][17][18][19][20][21][22] However, it is still a challenge to control the diastereoselectivity in such reactions, which is a vital task in pharmaceutical and bioorganic chemistry to supply any of the possible stereoisomers of the chiral product. 19,[23][24][25][26][27][28][29][30][31] Especially, only limited work was done on the catalytic direct asymmetric aldol reactions of cyclohexanone with aldehydes that afford syn-products. 32-34 Herein, we report diastereoselectivity control in the asymmetric aldol reaction of cycloketones with aldehydes, with moderate to good enantioselectivity. Chiral primary amine compounds had been discovered to be suitable catalysts for the asymmetric aldol reaction. [35][36][37][38][39][40] Different kinds of chiral amines (Scheme 1) were chosen as catalysts for the aldol reactions using 4-nitrobenzaldehyde and cyclohexanone as the model substrates (Table S1, ESIw).Our catalyst screening studies clearly demonstrated that chiral amine 1a combined with TFA could efficiently catalyze the asymmetric aldol reaction under solvent-free condition togive an ee of 97% and syn/anti ratio of 11/89. When the loading of chiral amine was reduced to as low as 2 mol%, the product was obtained with moderate yield (58%) and good enantioselectivity (83% ee). It is interesting to find that the syn/anti ratio increases to 31/69 when the amount of 1a was decreased to 2 mol%. All the other catalysts (1b-1g) under screening can also efficiently catalyze the asymmetric reactions with good to high enantioselectivity (83-96%). The syn/anti ratio of catalysts 1b to 1g is in the range of 25/75 to 47/53, which is higher than that of 1a. Though the syn/anti ratio can be increased by varying the structure of the chiral amine, it is still difficult to obtain the syn-b-hydroxy cyclohexanone as the main product.Diastereoselectivity control in these reactions depends on finding an appropriate catalyst based on reasonable analysis of the mechanism. The transition-state model (Scheme 2) shows that E-isomer of the enamine and steric hindrance between the cyclohexene ring and ...

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Brønsted Acid Catalyzed Asymmetric Aldol Reaction: A Complementary Approach to Enamine Catalysis

Abstract: A syn-enantioselective aldol reaction has been developed using Brønsted acid catalysis based on H(8)-BINOL-derived phosphoric acids. This method affords an efficient synthesis of various beta-hydroxy ketones, some of which could not be synthesized using enamine organocatalysis.

Cited by 97 publications

References 35 publications

Ionic Liquids: Synthesis and Applications in Catalysis

Ionic Liquids: Synthesis and Applications in Catalysis

Organocatalyzed Aldol Reactions

Acid controlled diastereoselectivity in asymmetric aldol reaction of cycloketones with aldehydes using enamine-based organocatalysts

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