Dipeptide-Catalyzed Asymmetric Aldol Condensation of Acetone with (N-Alkylated) Isatins

Luppi, Gianluigi; Cozzi, Pier Giorgio; Monari, Magda; Kaptein, Bernard; Broxterman, Quirinus B.; Tomasini, Claudia

doi:10.1021/jo050257l

Cited by 224 publications

(74 citation statements)

References 10 publications

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“…Dipeptide derivative (177, 10 mol%) provided the best results, among a set of 15 different dipeptides bearing α-or β-amino acid residues, in the reaction between acetone (52a, source of nucleophile and solvent) and isatins (166), leading to products 168 in good yields (90-99%) and moderate enantioselectivities (73-77%) [248]. Convolutamyne A (R 3 = 4,6-Br 2 and R 1 = H in 168, Scheme 3.40) was synthesized under similar reaction conditions in practical quantitative yield and 68% ee, which was increased up to >99% just by a recrystallization process [249].…”

Section: Ketones 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: Ketones As Electrophilesmentioning

confidence: 99%

Organocatalyzed Aldol Reactions

Guillena¹

2013

Modern Methods in Stereoselective Aldol Reactions

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“…Most of the reported peptide organocatalysts for the direct asymmetric aldol reaction are N-terminal prolyl dipeptides [20][21][22][23][24][25][26][27][28][29]. Córdova et al showed that amino acids [30,31] and small di-to tetra-peptides [32,33] with a primary amino functionality are able to catalyze the asymmetric intermolecular aldol reaction with high stereoselectivity.…”

Section: Introductionmentioning

confidence: 99%

l-Valine Dipeptide Organocatalysts with Two Amide Units for the Direct Asymmetric Aldol Reaction in Brine

Huang

Tian

et al. 2011

Catal Lett

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A series of valine dipeptide organocatalysts containing a primary amine group and two amide units have been developed and evaluated in the direct asymmetric intermolecular aldol reaction of 4-nitrobenzaldehyde and cyclohexanone. When 2,4-dinitrophenol (DNP) was used as an acidic additive, the catalyzed reactions of various aldehydes and ketones gave the corresponding aldol products with moderate to high enantioselectivities (up to 95%) and diastereoselectivities (up to [99/1, anti/ syn) in the presence of 3c in brine.

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“…The synthesis of 43 was achieved by the organocatalytic aldol reaction of acetone with 4,6-dibromoisatin (Scheme 33), an approach that had been used in an earlier study by Tomasini and co-workers for the coupling of acetone and isatin. [74] The catalyst employed was the d-prolinamide 42, which induced the formation of the quaternary carbon atom with the correct R configuration (the l-proline derivative afforded the S enantiomer preferentially). Under optimized conditions the natural product was obtained in almost quantitative yield.…”

Section: Methodsmentioning

confidence: 99%

Asymmetric Organocatalysis: From Infancy to Adolescence

2008

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After an initial period of validating asymmetric organocatalysis by using a wide range of important model reactions that constitute the essential tools of organic synthesis, the time has now been reached when organocatalysis can be used to address specific issues and solve pending problems of stereochemical relevance. This Review deals with selected studies reported in 2006 and the first half of 2007, and is intended to highlight four main aspects that may be taken as testimony of the present status and prospective of organocatalysis: a) chemical efficiency; b) discovery of new substrate combinations to give new asymmetric syntheses; c) development of new catalysts for specific purposes by using mechanistic findings; and d) applications of organocatalytic reactions in the asymmetric total synthesis of target natural products and known compounds of biological and pharmaceutical relevance.

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Dipeptide-Catalyzed Asymmetric Aldol Condensation of Acetone with (N-Alkylated) Isatins

Cited by 224 publications

References 10 publications

Organocatalyzed Aldol Reactions

Organocatalyzed Aldol Reactions

l-Valine Dipeptide Organocatalysts with Two Amide Units for the Direct Asymmetric Aldol Reaction in Brine

Asymmetric Organocatalysis: From Infancy to Adolescence

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