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The combination of a palladium complex with a chiral phosphoramidite ligand and a chiral phosphoric acid enables the first highly efficient asymmetric allylic alkylation of pyrazol-5-ones with allylic alcohols, affording multiply functionalized heterocyclic products in high yields with excellent enantioselectivities that would be of great potential in the synthesis of pharmaceutically interesting molecules.
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http://dx.doi.org/10.1021/ja402740q | DOI Listing |
Org Lett
September 2025
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, Maharashtra, India.
A concise and efficient asymmetric total synthesis of bicyclic-THP-lactone natural products passifetilactone D and cryptorigidifoliol I and four of the stereoisomers of proposed cryptorigidifoliol B has been achieved, enabled by Maruoka/Reetz or Maruoka/Brown allylations and Ghosez lactonization. Although the required diastereomers of cryptorigidifoliol B are synthesized now, with the mismatch of data to that of the natural isolate, its actual structure could not be ascertained, indicating a need for further structure revision.
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September 2025
State Key Laboratory of Precision and Intelligent Chemistry, Department of Chemistry, University of Science and Technology of China, Hefei 230026, P. R. China.
A novel palladium-catalyzed asymmetric aminomethylative pyridonation of conjugated dienes with -acetals and 2-hydroxypyridines was established, which provided a direct and reliable method for the synthesis of a wide range of γ-aminated N-substituted 2-pyridones with good to excellent enantioselectivities. The simple BF was identified as an effective cocatalyst to improve the reaction efficiency, and DFT calculations revealed that proton transfer between the aminomethylated allylic palladium species and 2-hydroxypyridine promoted by BF is crucial for obtaining good reactivity.
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September 2025
Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States.
An designed benzodioxin fused analogue of a des-(1-hydroxyethyl)-lincomycin analogue was synthesized in a asymmetric fashion from an achiral acylfuran, a 4-(-Pr)--methyl-proline, and catechol. The synthesis of the 6-amino-galactose portion of the lincomycin analogue necessitated the development of a novel stereospecific tandem Pd-glycosylation/1,4-addition reaction between catechol and an -Cbz-protected 6-amino-pyranone with a Pd-π-allyl leaving group at the -1 position. The desired -stereochemistry was installed by a subsequent stereoselective ketone reduction, alcohol elimination, and diastereoselective dihydroxylation of the -3/4 alkene.
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September 2025
School of Pharmaceutical Sciences & Institute of Materia Medica, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, Shandong, P. R. China.
In this work, we developed nucleophilic 2-aminoallyl cations guided by DFT calculations. Computational insights enabled a comprehensive analysis of factors governing N-nucleophilicity and an accurate prediction of cycloaddition reactivity with electron-deficient alkenes. Notably, this study represents the first asymmetric [3 + 2] cycloaddition of amino-allyl cations with exocyclic double bonds, enabling the efficient synthesis of -pyrrolidines with excellent diastereoselectivities and enantioselectivities.
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September 2025
Key Laboratory of Asymmetric Synthesis and Chirotechnology of Si-chuan Province, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China.
Based on a patented new concept of general chiral catalysis, a series of new chiral ligands integrating both a MacMillan imidazolinone organocatalyst and a chiral N,P-ligand scaffold has been designed and concisely prepared from commercially available chiral α-amino acids and 2-diphenylphosphino-benzaldehyde. These chiral ligands have shown good to excellent enantioselectivities (up to 97% ee) with satisfactory yields (up to 95%) in enantioselective Pd-catalyzed allylations with 1,3-dicarbonyls and amines.
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