Palladium-Catalyzed Asymmetric Hydrophosphination of Internal Alkynes: Highly Regio- and Stereoselective Construction of Axially Chiral Phosphines

Palladium-catalyzed unprecedented atroposelective hydrophosphination of internal alkynes has been realized using diarylphosphines, affording C-N axially chiral trisubstituted olefins (vinylphosphines) in excellent regioselectiviry, (E)-selectivity, and enantioselectivity. The axial chirality was established via integration of hydrophosphination and dynamic kinetic transformation of the alkynes, with both symmetrical and nonsymmetrical secondary phosphines being applicable. In the latter case, additional P-central chirality has been constructed in good diastereoselectivity.

Enantiodivergent Formation of C–P Bonds: Synthesis of P-Chiral Phosphines and Methyl-phosphonate Oligonucleotides

<p>A simple limonene-derived P(V)-based reagent for the modular, scalable, and stereospecific synthesis of chiral phosphines and methyl-phosphonate oligonucleotide (MPO) building blocks is presented. Built on a translimonene oxide (TLO) core, this formally triply electrophilic reagent class displays starkly differing reactivity from the cis-limonene oxide derived reagents reported previously [dubbed phosphorus-sulfur incorporation reagents or Ψ (PSI) for short]. These new phosphorus-incorporation reagents (PI, abbreviated as Π) access distinctly different chemical space than Ψ. The P(V)-manifold disclosed herein permits the stereochemically controlled sequential addition of carbon-based nucleophiles (from one to three) to produce a variety of enantiopure C–P bearing building blocks. When three carbon nucleophiles are added, useful P-chiral phosphines can be accessed after stereospecific reduction. When a single methyl group is added, the remaining nucleophiles can be nucleosides thus opening the door to the first stereospecific access to MPO-based oligonucleotide building blocks. Although both enantiomers of Π are available, only one isomer is required as the order of nucleophile addition controls the absolute stereochemistry of the final product through a unique enantiodivergent design.</p>

Enantiodivergent Formation of C–P Bonds: Synthesis of P-Chiral Phosphines and Methyl-phosphonate Oligonucleotides

<p>A simple limonene-derived P(V)-based reagent for the modular, scalable, and stereospecific synthesis of chiral phosphines and methyl-phosphonate oligonucleotide (MPO) building blocks is presented. Built on a translimonene oxide (TLO) core, this formally triply electrophilic reagent class displays starkly differing reactivity from the cis-limonene oxide derived reagents reported previously [dubbed phosphorus-sulfur incorporation reagents or Ψ (PSI) for short]. These new phosphorus-incorporation reagents (PI, abbreviated as Π) access distinctly different chemical space than Ψ. The P(V)-manifold disclosed herein permits the stereochemically controlled sequential addition of carbon-based nucleophiles (from one to three) to produce a variety of enantiopure C–P bearing building blocks. When three carbon nucleophiles are added, useful P-chiral phosphines can be accessed after stereospecific reduction. When a single methyl group is added, the remaining nucleophiles can be nucleosides thus opening the door to the first stereospecific access to MPO-based oligonucleotide building blocks. Although both enantiomers of Π are available, only one isomer is required as the order of nucleophile addition controls the absolute stereochemistry of the final product through a unique enantiodivergent design.</p>

Synthesis of P-chiral phosphine compounds by palladium-catalyzed C–P coupling reactions

An efficient C–P coupling reactions of enantiopure tert-butylmethylphosphine-boranes with aryl and heteroaryl halides is developed by using Pd(OAc)2/dppf as a catalyst, affording a series of P-chiral phosphines (up to 99% ee).