Enantiodivergent Formation of C–P Bonds: Synthesis of P‑Chiral Phosphines and Methylphosphonate Oligonucleotides

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.