Catalysis of Reactions by Amino Acids

Abstract

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).

Pd‐Catalyzed δ‐C(sp3)−H Thiolation of Amino Acid Derivatives

“…Amino acids (AAs) are bio-renewable, chiral C-and N-containing raw materials with many different applications. [1] Besides their biological function as building blocks of proteins, AAs with bulky side chains are important structural motifs in a broad range of organocatalysts, [2] ligands [3] and optimal structural backbones in pharmaceuticals [4] and agrochemicals. [5] Therefore, incorporating new functionalities into their structure is extremely useful to fine-tune their physicochemical properties [6] and physiological activity.…”

6-Alkynyl- and 6-Aryl-Substituted (R)-Pipecolic Acid Derivatives

“…Amino acids are versatile chiral pool building blocks in peptide chemistry, organic synthesis, and organocatalysis …”