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Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Stereocontrolled Substitution at P(III) Centers Enabled by Pyridine N-Oxide Catalysis
Bingbing Dong1,2, Zhongxian Li1, Yuanyuan Yin1
1High & New Technology Research Center, Henan Academy of Sciences, Zhengzhou 450002, P. R. China.
None:
A P(III)-based stereoselective substitution of phosphorodiamidites catalyzed by chiral pyridine N-oxide catalysts is disclosed. Unlike acid-promoted systems that suffer from stereorandom products and phosphites via uncontrolled multiple substitutions, this approach enables selective monosubstitution to deliver configurationally defined phosphoramidites (up to 4:96 dr). This enables stereoselective phosphitylation of various bioactive molecules, such as simvastatin, estradiol, uridine, and adenosine. Mechanistic studies supported by DFT calculations reveal a water-assisted covalent catalytic pathway.
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