Asymmetric Synthesis of Selectively Protected Amino Sugars and Derivatives by a Direct Organocatalytic Mannich Reaction

Enders, Dieter; Grondal, Christoph; Vrettou, Marianna; Raabe, Gerhard

doi:10.1002/anie.200500810

Cited by 170 publications

(31 citation statements)

References 64 publications

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“…The authors found that when (S)-proline was used, only traces of the desired products could be isolated, whereas the (R)-proline-catalyzed reaction provided the Mannich products in good yields (57-67%) and excellent stereoselectivity (>96% e.e.) [46]. The Mannich product obtained could be transformed into the corresponding bamino alcohol.…”

Section: Mechanismsmentioning

confidence: 99%

Catalysis of Reactions by Amino Acids

Xie

Hayes

Gathergood

2009

Amino Acids, Peptides and Proteins in Organic Chemistry

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j283 processes (Figure 7.2) [8]. As a result, proline has been studied as an effective catalyst and investigated for several powerful asymmetric transformations, such as the Aldol, Mannich, and Michael reactions. In addition, to provide opportunities for a better understanding of the origin of homochirality [9][10][11], amino acids as fundamental building blocks of organisms need to be investigated for their possible asymmetric transformation and amplification into prebiotic units such as sugars.Although amino acids, especially (S)-proline, have shown high efficiency in many valuable organic transformations affording corresponding products with high regio-, diastereo-, and enantioselectivities, sometimes such transformations suffered drawbacks. These include high catalyst loading, excess of nucleophile, long reaction times, and low solubility of catalyst in organic reaction media. To overcome these drawbacks and improve the catalytic performance of proline, some modifications to the structure of (S)-proline have been reported, thus allowing the fine-tuning of catalytic properties and improving the activities and conditions. Illustrated examples of modified amino acids are included in this chapter; however, several excellent recent reviews cover these derivatives in more detail [9-11].Scheme 7.2 Hajos-Parrish-Eder-Sauer-Wiechert reactions. Aldol Reaction j285Scheme 7.4 Organocatalytic transformation of 1,3-diketones into optically active cyclohexanones. 286j 7 Catalysis of Reactions by Amino Acids R 2 = Me, Et R 3 = H, Me Scheme 7.6 Asymmetric organocatalytic synthesis of cissubstituted dihydrobenzofuranols via intramolecular Aldol reactions. 7.2 Aldol Reaction j287 288j 7 Catalysis of Reactions by Amino Acids R 1 Scheme 7.9 (S)-Proline-catalyzed intermolecular Aldol reactions.290j 7 Catalysis of Reactions by Amino Acids Scheme 7.11 Organocatalytic enantioselective synthesis of a-hydroxy phosphonates. Aldol Reaction j291Scheme 7.14 Proline-catalyzed intermolecular Aldol reaction. Aldol Reaction j293Scheme 7.15 Two-step carbohydrate synthesis: iterative aldehyde aldol.294j 7 Catalysis of Reactions by Amino Acids D-sugars in most cases with >99% e.e. This two-step Aldol strategy opens up a novel route to enantiomerically pure d-lactones from simple aldehydes. For example, the hexoses obtained can be quantitatively converted into d-lactones by oxidation with MnO 2 (Scheme 7.18).

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Section: Mechanismsmentioning

confidence: 99%

Catalysis of Reactions by Amino Acids

Xie

Hayes

Gathergood

2009

Amino Acids, Peptides and Proteins in Organic Chemistry

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“…3 The first example of a direct organocatalytic three-component Mannich reaction was reported by List, 4 and followed by the excellent work of several groups. [5][6][7][8][9][10][11][12] Besides (S)-proline, 4-9 proline-derived tetrazole, 10 acylic amino acids and their derivatives, 11 and chiral phosphoric acids 12 were developed as enantioselective organocatalysts for the direct one-pot three component Mannich reactions. Although 1,2-amino alcohol can be constructed via Mannich reaction of hydroxyketone to imines, hydroxyacetone was seldom used as a donor in the asymmetric catalyzed direct Mannich reactions.…”

Section: Introductionmentioning

confidence: 99%

Organocatalytic Direct Asymmetric Mannich Reactions of Hydroxyacetone by (2S,5S)‐Pyrrolidine‐2,5‐dicarboxylic Acid

Gong

Jin

et al. 2008

Chin. J. Chem.

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“…Highly enantioselective Mannich reactions of dioxanone catalyzed by proline or its derivative were recently achieved; however, only syn-Mannich products were produced in those reactions (Scheme 1). [5,6] In addition, these reactions are limited in scope to the single DHA derivative 2,2-dimethyl-1,3-dioxane-5-one. Herein, we disclose a significant elaboration of our organocatalytic carbohydrate strategy as we describe the first organocatalytic anti-Mannich reactions of protected and unprotected DHA derivatives with a variety of aromatic and aliphatic aldehyde-derived imines.…”

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confidence: 99%

“…The use of DHA and DHA derivatives as C 3 synthons in organocatalytic Mannich reactions promise efficient syntheses of amine-containing sugars. [5,6] Despite considerable attention afforded to the catalytic asymmetric aldol reactions of DHA and DHA derivatives, [4] these substrates are not well explored in organocatalytic Mannich and Mannich-type reactions. Highly enantioselective Mannich reactions of dioxanone catalyzed by proline or its derivative were recently achieved; however, only syn-Mannich products were produced in those reactions (Scheme 1).…”

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Organocatalytic anti‐Mannich Reactions with Dihydroxyacetone and Acyclic Dihydroxyacetone Derivatives: A Facile Route to Amino Sugars

Zhang¹,

Ramasastry²,

Tanaka³

et al. 2008

Adv Synth Catal

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Abstract:The first primary amine-containing amino acid-catalyzed anti-Mannich reactions of dihydroxy-A C H T U N G T R E N N U N G acetone and acyclic dihydroxyacetone derivatives with a variety of imines have been developed. This approach complements proline-based strategies in the preparation of amino sugars.Keywords: acyclic dihydroxyacetone derivatives; anti-Mannich reaction; dihydroxyacetone; primary amine-containing amino acids Amino and imino sugars are of significant interest not only for use as tools in glycobiology but also for the treatment of a range of human diseases ranging from HIV-1 and hepatitis C infections to genetic disorders like Gauchers disease and other inborn errors of metabolism. Consequently, there has been significant interest in the development of efficient syntheses of these types of compounds. [1,2] Typically, these sugars require multistep syntheses.[3] The most expedient de novo syntheses use aldolase enzymes or organocatalytic aldol reactions involving dihydroxyacetone (DHA) derivatives.[4] Although aldol-based DHA routes are efficient, this approach is limited with respect to the placement of the amino functionality within the target sugar. Enzyme-based strategies based on DHA are limited to the aldol reaction since the enzymes do not accept Mannich imine acceptors.Direct catalytic asymmetric Mannich reactions have emerged as a powerful class of C À C bond-forming reactions that provide access to optically enriched nitrogen-containing compounds. The use of DHA and DHA derivatives as C 3 synthons in organocatalytic Mannich reactions promise efficient syntheses of amine-containing sugars. [5,6] Despite considerable attention afforded to the catalytic asymmetric aldol reactions of DHA and DHA derivatives, [4] these substrates are not well explored in organocatalytic Mannich and Mannich-type reactions. Highly enantioselective Mannich reactions of dioxanone catalyzed by proline or its derivative were recently achieved; however, only syn-Mannich products were produced in those reactions (Scheme 1). [5,6] In addition, these reactions are limited in scope to the single DHA derivative 2,2-dimethyl-1,3-dioxane-5-one. Herein, we disclose a significant elaboration of our organocatalytic carbohydrate strategy as we describe the first organocatalytic anti-Mannich reactions of protected and unprotected DHA derivatives with a variety of aromatic and aliphatic aldehyde-derived imines.As one part of our ongoing program to meet the stereochemical challenges in Mannich chemistry that are not addressed with proline and its derivatives, we have recently developed efficient anti-Mannich strategies. [7,8] In our previous anti-Mannich studies, we demonstrated an efficient route to highly enantiomerically enriched anti-1,2-amino alcohols by employing unmodified hydroxyacetone and proposed the intermediacy of a hydrogen bond-stabilized (Z)-enamine Scheme 1.

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Asymmetric Synthesis of Selectively Protected Amino Sugars and Derivatives by a Direct Organocatalytic Mannich Reaction

Cited by 170 publications

References 64 publications

Catalysis of Reactions by Amino Acids

Catalysis of Reactions by Amino Acids

Organocatalytic Direct Asymmetric Mannich Reactions of Hydroxyacetone by (2S,5S)‐Pyrrolidine‐2,5‐dicarboxylic Acid

Organocatalytic anti‐Mannich Reactions with Dihydroxyacetone and Acyclic Dihydroxyacetone Derivatives: A Facile Route to Amino Sugars

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