A highly efficient and asymmetric process to achieve spirocyclic 4-aminopyrazolone derivatives through a cascade Michael addition/cyclization reaction of 4-isothiocyanato pyrazolones with 3-ylideneoxindoles was developed. This reaction forged multicyclic dispiro[pyrazolone-pyrrolidinethione-oxindole] core structures bearing three contiguous stereogenic centers, including two spiro-quaternary stereocenters with excellent diastereo- and enantioselectivities (up to 99% ee, >20 : 1 dr). The product can be readily diversified to expand the chemical space of spiropyrazolone species. A plausible mechanism to account for the stereochemical course of the cascade process was proposed.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1039/d0cc04215c | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Enantioselective construction of silicon-stereogenic vinylsilanes from simple alkenes.
Nat Commun
January 2025
State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Frontiers Science Center for New Organic Matter, Haihe Laboratory of Sustainable Chemical Transformations, Nankai University 94 Weijin Road, Tianjin, China.
The diverse utility of acyclic vinylsilanes has driven the interest in the synthesis of enantioenriched vinylsilanes bearing a Si-stereogenic center. However, the predominant approaches for catalytic asymmetric generation of Si-stereogenic vinylsilanes have mainly relied on transition metal-catalyzed reactions of alkynes with different silicon sources. Here we successfully realize the enantioselective synthesis of linear silicon-stereogenic vinylsilanes with good yields and enantiomeric ratios from simple alkenes under rhodium catalysis.
View Article and Find Full Text PDFTaming Highly Enolizable Aldehydes via Enzyme Catalysis for Enantiocomplementary Construction of β-Hydroxyphosphonates.
J Am Chem Soc
January 2025
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
Taming highly enolizable aldehydes for catalytic asymmetric C-C coupling with nucleophiles remains an elusive challenge compared to widely explored simple alkyl or aryl aldehydes. Herein, we use ThDP-dependent enzymes to realize the direct C-C coupling of highly enolizable 2-phosphonate aldehydes with in situ-generated dynamically reversible nucleophiles (acyl anions). Unlike NHC-mediated reactions that yield complex mixtures of multiple adducts, our enzymatic process selectively produces biologically active β-hydroxy phosphonates with high yields (up to 95%) and excellent enantioselectivities (up to 99% ee).
View Article and Find Full Text PDFEngineered enzymes for enantioselective nucleophilic aromatic substitutions.
Nature
January 2025
Manchester Institute of Biotechnology, The University of Manchester, Manchester, UK.
Nucleophilic aromatic substitutions (SAr) are amongst the most widely used processes in the pharmaceutical and agrochemical industries, allowing convergent assembly of complex molecules through C-C and C-X (X = O, N, S) bond formation. SAr reactions are typically carried out using forcing conditions, involving polar aprotic solvents, stoichiometric bases and elevated temperatures, which do not allow for control over reaction selectivity. Despite the importance of SAr chemistry, there are only a handful of selective catalytic methods reported that rely on small organic hydrogen-bonding or phase-transfer catalysts.
View Article and Find Full Text PDFStrained Dehydro-[2,2]-paracyclophane Enabled Planar Chirality Construction and [2.2]Paracyclophane Functionalization.
Angew Chem Int Ed Engl
January 2025
Shandong University, Department of Chemistry, 27 South Shanda Road, 250100, Jinan, CHINA.
Planar chirality found tremendous use in many fields, such as chemistry, optics, and materials science. In particular, planar chiral [2.2]paracyclophanes (PCPs) are a type of structurally interesting and practically useful chiral compounds bearing unique electronic and photophysical properties and thus have been widely used in π-stacking polymers, organic luminescent materials, and as a valuable toolbox for developing chiral ligands or organocatalysts.
View Article and Find Full Text PDFCFH-synthon enables asymmetric radical difluoroalkylation for synthesis of chiral difluoromethylated amines.
Nat Commun
January 2025
Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
The difluoromethyl group is a crucial fluorinated moiety with distinctive biological properties, and the synthesis of chiral CF₂H-containing analogs has been recognized as a powerful strategy in drug design. To date, the most established method for accessing enantioenriched difluoromethyl compounds involves the enantioselective functionalization of nucleophilic and electrophilic CF₂H synthons. However, this approach is limited by lower reactivity and reduced enantioselectivity.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!