The catalytic enantioselective diorganozinc additions to cyclic diketones including pyrazolin-4,5-diones and isatins have been developed. In the presence of morpholine-containing chiral amino alcohol ligand, the corresponding chiral cyclic tertiary alcohols were produced in good to excellent yields (up to 97 %) and enantioselectivities (up to 95 % ee). The notable feature of this protocol includes its mild reaction conditions, Lewis acid additives free and broad functional group tolerance.
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http://dx.doi.org/10.1002/chem.202005081 | DOI Listing |
Nat Commun
January 2025
Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, China.
Flow chemistry has many advantages over batch synthesis of organic small-molecules in terms of environmental compatibility, safety and synthetic efficiency when scale-up is considered. Herein, we report the 10-step chemo-biocatalytic continuous flow asymmetric synthesis of cyproterone acetate (4) in which 10 transformations are combined into a telescoped flow linear sequence from commercially available 4-androstene-3, 17-dione (11). This integrated one-flow synthesis features an engineered 3-ketosteroid-Δ-dehydrogenase (ReM2)-catalyzed Δ-dehydrogenation to form the C1, C2-double bond of A ring, a substrate-controlled Co-catalyzed Mukaiyama hydration of 9 to forge the crucial chiral C17α-OH group of D ring with excellent stereoselectivity, and a rapid flow Corey-Chaykovsky cyclopropanation of 7 to build the cyclopropyl core of A ring.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
Shanghai Jiao Tong University, Frontiers Science Center for Transformative Molecules, 800 Dongchuan Road, 200240, Shanghai, CHINA.
Along with the renaissance of radical chemistry, the past decade has witnessed rapid development in radical-mediated rearrangement reactions. A wide diversity of radical approaches harnessing functional-group migration (FGM) have been devised to enhance both synthetic efficiency and molecular complexity. However, the application of FGM reactions to construct stereogenic centers remains underexplored owing to the inherent challenges of asymmetric radical reactions.
View Article and Find Full Text PDFOrg Lett
January 2025
Institute of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8571, Japan.
Multiple Diels-Alder reactions are a powerful method to construct large asymmetric scaffolds, but these reactions often produce numerous isomers. We now report a triple Diels-Alder reaction between a cyclic furan trimer and -substituted maleimides, achieving selective synthesis of a single asymmetric tris-adduct. The stereoselectivity of cycloaddition to π-extended furan derivatives was clarified by the experimental analysis of intermediates and theoretical calculations.
View Article and Find Full Text PDFEnzymatic asymmetric synthesis of l-phenylglycine by amino acid dehydrogenases has potential for industrial applications; however, this is hindered by their low catalytic efficiency toward high-concentration substrates. We identified and characterized a novel leucine dehydrogenase (LeuDH) with a high catalytic efficiency for benzoylformic acid via directed metagenomic approaches. Further, we obtained a triple-point mutant LeuDH-EER (D332E/G333E/L334R) with improved stability and catalytic efficiency through the rational design of distal loop 13.
View Article and Find Full Text PDFChem Soc Rev
January 2025
Pingyuan Laboratory, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, 453007, Henan, P. R. China.
The use of olefins in the construction of cyclic compounds represents a powerful strategy for advancing the pharmaceutical industry. Photocycloaddition has attracted significant interest from chemists due to its ability to exploit simple and readily available olefins along with their reaction patterns under mild conditions. Moreover, the sustainable and versatile pathways for generating highly reactive intermediates can greatly enrich both substrate diversity and reaction patterns.
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