Direct Organocatalytic Asymmetric Aldol Reactions of α-Amino Aldehydes:  Expedient Syntheses of Highly Enantiomerically Enriched <i>a</i><i>nti</i>-β-Hydroxy-α-amino Acids

Thayumanavan, Rajeswari; Tanaka, Fujie; Barbas, Carlos F.

doi:10.1021/ol0485417

Cited by 149 publications

(51 citation statements)

References 57 publications

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“…[19,20] But its incorporation into multidentate ligands that leads to five-membered chelate rings upon complexation has not yet been attempted. In the domains of medicinal chemistry and drug design, [21,22] and lately also more frequently in organocatalysis, [23][24][25][26] the tetrazole moiety is of particular interest as a carboxylic acid "isoster". [27] Here, it is usually established in situ with the corresponding inconveniences (reactant incompatibility, yield).…”

Section: Resultsmentioning

confidence: 99%

A Tetrakis(tetrazolyl) Analogue of EDTA

2009

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International audienceThe tetrazole moiety is usually established in situ with the corresponding inconveniences, such as reactant incompatibility, yield. In most of these cases, the tetrazole is formed in its nonprotected form. Subsequent protection is unattractive because of the promiscuous formation of two regioisomers. No particular protecting group has seen widespread use. The growing field of site-selective oxidation of unactivated hydrocarbons makes use of metal complexes based on multidentate ligands displaying nitrogen coordination sites. We have characterized an easily accessible, benzyl-protected synthon that allows the convergent introduction of the tetrazolylmethyl moiety and its smooth deprotection by catalytic hydrogenation. With the straightforward synthesis of the new hexadentate ligand EDTT, we have demonstrated the utility of this synthon for the fields of coordination, medicinal, and organocatalytic chemistry

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Section: Resultsmentioning

confidence: 99%

A Tetrakis(tetrazolyl) Analogue of EDTA

2009

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“…The reaction of a glycine aldehyde derivative with an excess of different aldehydes gave an anti-b-hydroxy-a-amino aldehyde as the main product [36].…”

Section: Intermolecular Aldol Reactionmentioning

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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“…L-Proline-catalyzed asymmetric cross-aldol reactions The proline-catalyzed asymmetric cross-aldol reaction is also effective with N-protected aminoacetaldehydes as an aldehyde donor, and provides an expedient way to anti-β-hydroxy-α-amino acid derivatives (Scheme 19). 60 The application of an asymmetric cross-aldol reaction of this type in conjunction with other methods of forming carbon-carbon bonds, such as metal-mediated allylations, On the other hand, Pearson and coworkers developed a much more ingenious strategy based on intramolecular asymmetric aldol reactions of meso-dialdehydes for preparing tropane alkaloid skeletons (Scheme 21). 63 Thus, a 5-step conversion of the aldol adduct gave the total synthesis of (+)-cocaine with 86% ee.…”

Section: Cross-aldol Reactionsmentioning

confidence: 99%

Organocatalytic Asymmetric Synthesis Using Proline and Related Molecules. Part 2.

Kotsuki¹,

Ikishima²,

Okuyama³

2008

HETEROCYCLES

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-Organocatalytic asymmetric synthesis has been extensively studied and several important procedures for preparing optically active organic compounds have been developed. Research in this area has progressed rapidly in the last ten years. This review addresses the most significant advances in asymmetric synthesis using proline and related chiral organocatalysts mainly focusing on aldol reactions from the viewpoint of synthetic interests. This includes (1) proline-catalyzed aldol reactions, (2) proline-related chiral catalysts, and (3) other types of amino acid catalysts.

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Direct Organocatalytic Asymmetric Aldol Reactions of α-Amino Aldehydes: Expedient Syntheses of Highly Enantiomerically Enriched anti-β-Hydroxy-α-amino Acids

Cited by 149 publications

References 57 publications

A Tetrakis(tetrazolyl) Analogue of EDTA

A Tetrakis(tetrazolyl) Analogue of EDTA

Catalysis of Reactions by Amino Acids

Organocatalytic Asymmetric Synthesis Using Proline and Related Molecules. Part 2.

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