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. 2024 Mar 8;9(11):12657-12664.
doi: 10.1021/acsomega.3c07948. eCollection 2024 Mar 19.

New Strategy for the Synthesis of Some Valuable Chiral 1,3-Diols with High Enantiomeric Purity: New Organocatalyst, Asymmetric Aldol Reaction, and Reduction

Tülay Yıldız  1 , Belma Hasdemir  1 , Hasniye Yaşa  1 , Hatice Başpınar Küçük  1
Affiliations

New Strategy for the Synthesis of Some Valuable Chiral 1,3-Diols with High Enantiomeric Purity: New Organocatalyst, Asymmetric Aldol Reaction, and Reduction

Tülay Yıldız et al. ACS Omega. .

Abstract

Chiral 1,3-diols are highly valuable molecules used in industries such as pharmaceuticals, cosmetics, and agriculture. Therefore, in this study, a new strategy was developed to synthesize enantiomerically pure (>99% ee) 1,3-diols. New chiral 1,3-diols (5a-5q) with high enantiomeric purity were synthesized from aldol products chiral 1,3-keto alcohols (4a-4q), which are aldol products with different structures. Chiral 1,3-keto alcohols (4a-4q) were synthesized by a new asymmetric aldol method in the first step. This method was developed using a new proline-derived organocatalyst (3g) and Cu(OTf)2 as an additive in DMSO-H2O for the first time. Almost >99% ee was obtained using our developed aldol procedure. In the second step, original chiral diols (5a-5q) of high enantiomeric purity were obtained by asymmetric reduction of chiral keto alcohols with chiral oxazaborolidine reagents. In this way, a two-step asymmetric reaction was developed for chiral 1,3-diol enantiomers with high enantiomeric purity. The structures of all the original chiral compounds obtained were elucidated by infrared and nuclear magnetic resonance spectroscopy, mass spectrometry, and elemental analysis methods. Their enantiomeric excesses were determined by the chiral high-performance liquid chromatography method. Both keto alcohols and their corresponding chiral diols synthesized can be used as chiral starting materials and chiral source materials or intermediates in the synthesis of many biologically active molecules, or they can be used as chiral ligands in asymmetric synthesis, serving as organocatalysts.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Some important applications of chiral 1,3-diols.
Figure 2
Figure 2
Organocatalysts used for the asymmetric aldol reactions.
Figure 3
Figure 3
Postulated mechanism of the new aldol method.
See this image and copyright information in PMC

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