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Enantiodivergent Formation of C–P Bonds: Synthesis of P‑Chiral Phosphines and Methylphosphonate Oligonucleotides
journal contribution
posted on 2020-03-13, 20:04 authored by Dongmin Xu, Nazaret Rivas-Bascón, Natalia M. Padial, Kyle W. Knouse, Bin Zheng, Julien C. Vantourout, Michael A. Schmidt, Martin D. Eastgate, Phil S. BaranPhosphorus 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 requiredthe
order of nucleophile addition controls the absolute stereochemistry
of the final product through a unique enantiodivergent design.