Asymmetric organocatalysis has been recognized as one of the "top 10 emerging technologies" in chemistry by IUPAC in 2019. Its potential to make chemical processes more sustainable is promising, but there are still challenges that need to be addressed. Developing new and reliable enantioselective processes for reproducing batch reactions on a large scale requires a combination of chemical and technical solutions. In this manuscript, we combine a robust immobilized chiral phosphoric acid with a new packed-bed reactor design. This combination allows scaling up of the enantioselective addition of thiols to imines from a few milligrams to a multi-decagram scale in a continuous flow process without physical or chemical degradation of the catalyst.
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http://dx.doi.org/10.1039/d4gc00019f | DOI Listing |
Org Lett
January 2025
School of Chemistry and Chemical Engineering/State Key Laboratory Incubation Base for Green Processing of Chemical Engineering, Shihezi University, Shihezi, Xinjiang 832003, China.
A chiral phosphoric acid-catalyzed efficient, operationally simple, general method for straightforward syntheses of axially chiral arylpyrazole employing -alkyl of 3-aryl-5-aminopyrazoles reacting with azonaphthalenes was achieved. A wide variety of axially chiral heterobiaryl diamines in generally good yields with excellent enantioselectivities were obtained under mild conditions. In addition, a scaled-up experiment and postmodification of the chiral product further highlighted the synthetic utility.
View Article and Find Full Text PDFOrg Lett
January 2025
Pingyuan Laboratory, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, People's Republic of China.
An asymmetric photoredox catalytic Minisci-type reaction between α-bromide amides and imine-containing azaarenes has been successfully developed. This catalyst system employs a chiral phosphoric acid alongside 3DPAFIPN as a photosensitizer. The reaction produces a diverse array of valuable amides, featuring azaarene-substituted tertiary carbon stereocenters at the β-position, in high yields (up to 85%) and good to excellent enantioselectivities (up to >99% enantiomeric excess (ee)).
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Frontiers Science Center for Transformative Molecules, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
Direct synthesis of enantioenriched scaffolds with multiple adjacent stereocenters remains an important yet challenging task. Herein, we describe a highly diastereo- and enantioselective Cu-catalyzed alkylboration of cyclopropenes, with less reactive alkyl iodides as electrophiles, for the efficient synthesis of -substituted borylated cyclopropanes bearing three consecutive stereocenters. This protocol features mild conditions, a broad substrate scope, and good functional group tolerance, affording an array of chiral borylated cyclopropanes in good to high yields with excellent diastereo- and enantioselectivities.
View Article and Find Full Text PDFAnal Chem
January 2025
School of Petrochemical Engineering, Liaoning Petrochemical University, Fushun 113001, China.
Chiral discrimination is an indispensable tool that has pivotal importance in the assignment of absolute configuration and determination of enantiomeric excess in chiral compounds. A series of enantiomerically pure -1,2-diaminocyclohexane (-DACH)-derived benzamides were first synthesized by simple chemical steps, and 14 variated derivatives have been assessed as NMR chiral solvating agents (CSAs) for discrimination of the signals of mandelic acid (MA) in H NMR analysis. The highly efficient chiral recognition of CSA on different substrates, including MAs, carboxylic acids, amino acid derivatives, and phosphoric acids (32 examples), was expanded via H, F, and P NMR spectroscopy.
View Article and Find Full Text PDFSpectrochim Acta A Mol Biomol Spectrosc
January 2025
Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, 160 00 Prague, Czech Republic. Electronic address:
Model P-chirogenic phosphonates derived from isopinocampheol, offering an excellent experimental system for studying chirality on the phosphorus chiral center, were studied using a set of chiroptical methods including ECD, VCD and ROA. Thanks to their rigidity, limiting the number of possible conformers, we successfully correlated the experimental UV-vis/ECD, IR/VCD and Raman/ROA results with DFT calculations. This allowed us to confidently assign the absolute configuration of our models, and our assignment is consistent with X-ray diffraction (XRD) data.
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