Enantiodivergent Formation of C-P Bonds: Synthesis of P-Chiral Phosphines and Methylphosphonate Oligonucleotides.

Dongmin Xu, Nazaret Rivas-Bascón, Natalia M Padial, Kyle W Knouse, Bin Zheng, Julien C Vantourout, Michael A Schmidt, Martin D Eastgate, Phil S Baran

Journal of the American Chemical Society 2020 Mar 25

filter terms:

Phosphorus Incorporation (PI, abbreviated Π) reagents for the modular, scalable, and stereospecific synthesis of chiral phosphines and methylphosphonate nucleotides are reported. Synthesized from trans-limonene oxide, this reagent class displays an unexpected reactivity profile and enables access to chemical space distinct from that of the Phosphorus-Sulfur Incorporation reagents previously disclosed. Here, the adaptable phosphorus(V) scaffold enables sequential addition of carbon nucleophiles to produce a variety of enantiopure C-P building blocks. Addition of three carbon nucleophiles to Π, followed by stereospecific reduction, affords useful P-chiral phosphines; introduction instead of a single methyl group reveals the first stereospecific synthesis of methylphosphonate oligonucleotide precursors. While both Π enantiomers are available, only one isomer is required-the order of nucleophile addition controls the absolute stereochemistry of the final product through a unique enantiodivergent design.

Citation

Dongmin Xu, Nazaret Rivas-Bascón, Natalia M Padial, Kyle W Knouse, Bin Zheng, Julien C Vantourout, Michael A Schmidt, Martin D Eastgate, Phil S Baran. Enantiodivergent Formation of C-P Bonds: Synthesis of P-Chiral Phosphines and Methylphosphonate Oligonucleotides. Journal of the American Chemical Society. 2020 Mar 25;142(12):5785-5792