Preparation of Enantiomerically Pure β,β‐Diaryl β‐Hydroxy‐α‐Amino Acids and Evaluation of Their Potential as Organocatalysts

Abstract

A general synthetic procedure was developed for enantiomerically pure β,β‐diaryl β‐hydroxy‐α‐amino acids 5, starting from readily available oxazolidine ester 1 and a wide variety of Grignard reagents. The problematic oxidative decomposition of β‐aminodiols 3, due to their instability in the presence of metallic oxidants, was successfully suppressed using Parikh‐Doering oxidation and subsequent Pinnick oxidation. Additionally, the organocatalytic ability of β,β‐diaryl β‐hydroxy‐α‐amino acids 5 was evaluated with respect to asymmetric fluorination of 2‐phenylpropionaldehyde 6, and moderate enantioselectivity, 61%, was achieved using compound 5 f.

Stereoselective Synthesis and Catalytical Application of Perillaldehyde-Based 3-Amino-1,2-diol Regioisomers

“…For example, cytoxazone, a microbial metabolite isolated from Streptomyces species, is a selective modulator of the secretion of TH2 cytokine [14,15]. Besides their biological interest, aminodiols have also been applied as starting materials in asymmetric syntheses or as chiral auxiliaries and ligands in enantioselective transformations [1,[16][17][18]. To develop new, efficient, and commercially available chiral catalysts, chiral natural products including (+)-and (−)-α-pinene [19,20], (−)-nopinone [21], (+)carene [22,23], (+)-sabinol [24], (−)-pulegone [25], or camphore and fenchon [26] can serve as important starting materials for the synthesis of aminodiols.…”

Enantioselective Fluorination of α-Substituted β-Diketones Using β,β-Diaryl Serines

“…Although many enantioselective reactions using amino acids as organocatalysts have been developed so far, the structural variation of primary amino acids is strictly limited to proteogenic amino acids; therefore, some reactions still yield unsatisfactory results. Recently, we have developed a new synthesis of β,β-diaryl serines, which can easily modify the steric and electronic properties of primary amino acids . In this light, we aimed to explore the enantioselective fluorination of α-substituted β-diketones using our developed β,β-diaryl serines as a bifunctional primary amine catalyst.…”

“…Recently, we have developed a new synthesis of β,β-diaryl serines, which can easily modify the steric and electronic properties of primary amino acids. 17 In this light, we aimed to explore the enantioselective fluorination of α-substituted β-diketones using our developed β,β-diaryl serines as a bifunctional primary amine catalyst.…”