A concise organocatalytic and enantioselective synthesis of isotetronic acids

Vincent, Jean‐Marc; Margottin, Chrystèle; Berlande, Muriel; Cavagnat, D.; Buffeteau, Thierry; Landais, Yannick

doi:10.1039/b711192d

Cited by 48 publications

(24 citation statements)

References 43 publications

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“…We thus turned our attention to ligands 23-26 ( Figure 3) using CuA C H T U N G T R E N N U N G (OTf) 2 [34] and Zn-A C H T U N G T R E N N U N G (OTf) 2 [35] as catalysts (Table 3). Ligand 26, recently developed in our laboratory, [36] led to interesting results in terms of yield and enantioselectivity, with better selectivity (82 % ee) being obtained at 0 8C (Table 3, entry 6). The best results were observed with copper, which led to an encouraging 93 % ee using sterically hindered (S,S)-Box-tBu 23 b (Table 3, entry 2).…”

Section: Resultsmentioning

confidence: 99%

Development of Domino Processes by Using 7‐Silylcycloheptatrienes and Its Analogues

Beniazza

Desvergnes

Girard

et al. 2012

Chemistry A European J

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7-Silyl- and 7-silylmethylcycloheptatrienes were shown to react with acylnitroso reagents at room temperature, through their norcaradiene forms, to generate the corresponding cycloadducts 5 a-b and 6 a-b as single diastereomers. The course of the reaction was dramatically modified by changing the reaction conditions. Using a polar medium, functionalized cyclohexa-1,3-dienes 7 a-b and bicyclic compounds 13 a-b were instead generated, incorporating one or two amino groups. Similar behavior was observed by using other dienophiles, including triazolinedione, but also activated aldehydes and ketones. A tentative mechanism has been proposed to rationalize the formation of both classes of products that relies on a domino process involving four consecutive elementary steps, in this order: 1) electrocyclic process, 2) hetero-Diels-Alder reaction, 3) cyclopropane ring opening, and 4) hetero-Diels-Alder reaction. Trapping of the cationic intermediate and isolation of the primary cycloadduct provide support for this hypothesis. An enantioselective version of the cascade using cycloheptatriene 4 b and aldehydes and ketones, under copper(II) catalysis was also carried out, leading to cyclohexa-1,3-dienes 21, 28, and 30 with enantioselectivities up to 93 % ee. Finally, elaboration of the intermediates above has been carried out, opening a straightforward access to sugar mimics 42-43 and complex polycyclic systems 36 and 39.

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Section: Resultsmentioning

confidence: 99%

Development of Domino Processes by Using 7‐Silylcycloheptatrienes and Its Analogues

Beniazza

Desvergnes

Girard

et al. 2012

Chemistry A European J

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“…Initially, the reaction gave a complicate mixture of different products derived from the aldol process, but with the use of polymer-supported sulfonic acid Amberlist 15, to eliminate the catalyst, and the final treatment of reaction mixture with a silylating agent, the product 295 was isolated in reasonable yields [348]. Similarly, compound 267b (10 or 30 mol%) catalyzed the synthesis of isotetronic acids by reaction of an equimolecular mixture of pyruvic acid with aliphatic or aromatic aldehydes 53, affording products of type 295 in moderate results (10-77% yield, 36-90% ee) [349].…”

Section: Application To Natural Product Synthesismentioning

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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“…Amongst the various aldol processes that have been catalyzed by compound I , a straightforward synthesis of isotetronic acids 3 from α‐ketoacids (e.g. 2 ) and aromatic or aliphatic aldehydes was developed, thus leading to the desired five‐membered rings in high yields and with high enantioselectivities 4. This work complemented previous approaches to isotetronic acids by using chiral auxiliaries, organometallic catalysis, and proline‐catalyzed pyruvate homo‐aldol reactions and represents one of the few examples of organocatalyzed asymmetric aldol reactions that exploit 1,2‐dicarbonyl compounds as pronucleophiles 5…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, complete hydrogenation of the pyridinium salts 4 eventually led to the corresponding non‐natural indolizidines8 in good yields and with high enantiocontrol in only two steps from commercially available precursors. This reaction likely proceeded through the stereoselective addition of an enamine that was formed from the α‐ketoacid 2 and catalyst I onto the aldehyde functional group of pyridine 1 ; subsequent lactonization provided compound 3 4. Alternatively, the resulting aldol product may evolve through the attack of the pyridine nitrogen atom onto the electrophilic α‐keto group to provide compound 4 .…”

Section: Introductionmentioning

confidence: 99%

Organocatalyzed Aldol Reaction between Pyridine‐2‐carbaldehydes and α‐Ketoacids: A Straightforward Route towards Indolizidines and Isotetronic Acids

Liautard

Jardel

Davies

et al. 2013

Chemistry A European J

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Enantioselective aldol reactions between substituted pyridine carbaldehydes and α-ketoacids were shown to provide isotetronic acids or their corresponding pyridinium salts, depending on the nature of the substituents on the pyridine ring. The pyridinium salts were generated through nucleophilic attack of the pyridine nitrogen atom onto the reactive keto functional group. Moderate-to-good yields of both compounds were typically obtained and high levels of enantioselectivity were observed by using benzimidazole pyrrolidine I as a catalyst. Hydrogenation of the resulting pyridinium salts led to new indolizidines with high ee values and diastereocontrol. X-ray diffraction studies allowed the determination of the relative configuration of the products. Finally, DFT calculations were performed to rationalize the divergent pathway as a function of the pyridine substituents.

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A concise organocatalytic and enantioselective synthesis of isotetronic acids

Abstract: A concise enantioselective route to isotetronic acids using an organocatalyzed aldol reaction between alpha-oxocarboxylic acids and aldehydes has been developed, leading to the titled compounds in reasonable yields and good enantioselectivities.

Cited by 48 publications

References 43 publications

Development of Domino Processes by Using 7‐Silylcycloheptatrienes and Its Analogues

Development of Domino Processes by Using 7‐Silylcycloheptatrienes and Its Analogues

Organocatalyzed Aldol Reactions

Organocatalyzed Aldol Reaction between Pyridine‐2‐carbaldehydes and α‐Ketoacids: A Straightforward Route towards Indolizidines and Isotetronic Acids

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