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.