Primary Phosphines and Phosphine Oxides with a Stereogenic Carbon Center Adjacent to the Phosphorus Atom: Synthesis and Anti-Markovnikov Radical Addition to Alkenes

Organophosphorus compounds with stereogenic phosphorus and carbon atoms have received increasing attention. In this regards, primary phosphines with a stereogenic carbon atom adjacent to the phosphorus atom were synthesized by the reduction in phosphonates and phosphonoselenoates with a binaphthyl group. Their oxidized products, i.e., phosphine oxides with a stereogenic tetrasubstituted carbon atom, were found to undergo BEt3-mediated radical addition to cyclohexene to give P-stereogenic secondary phosphine oxides with a diastereoselectivity of 91:9. The products were characterized by ordinary analytical methods, such as Fourier transform infrared spectroscopy; 1H, 13C, and 31P NMR spectroscopies; and mass spectroscopy. Computational studies on the phosphorus-centered radical species and the obtained product implied that the thermodynamically stable radical and the adduct may be formed as a major diastereomer. The radical addition to a range of alkenes took place in an anti-Markovnikov fashion to give P-stereogenic secondary phosphine oxides. A variety of functional groups in the alkenes were tolerated under the reaction conditions to afford secondary phosphine oxides in moderate yields. Primary phosphines with an alkenyl group, which were generated in situ, underwent intramolecular cyclization to give five- and six-membered cyclic phosphines in high yields after protection by BH3.

Electron-Deficient Acetylenes as Three-Modal Adjuvants in SNH Reaction of Pyridinoids with Phosphorus Nucleophiles

Publications covering a new easy metal-free functionalization of pyridinoids (pyridines, quinolines, isoquinolines, acridine) under the action of the system of electron-deficient acetylenes (acetylenecarboxylic acid esters, acylacetylenes)/P-nucleophiles (phosphine chalcogenides, H-phosphonates) are reviewed. Special attention is focused on a SNH reaction of the regioselective cross-coupling of pyridines with secondary phosphine chalcogenides triggered by acylacetylenes to give 4-chalcogenophosphorylpyridines. In these processes, acetylenes act as three-modal adjuvants (i) activating the pyridine ring towards P-nucleophiles, (ii) deprotonating the P-H bond and (iii) facilitating the nucleophilic addition of the P-centered anion to a heterocyclic moiety followed by the release of the selectively reduced acetylenes (E-alkenes).

Secondary Phosphine Oxide-Activated Nickel Catalysts for Site-Selective Alkene Isomerization and Remote Hydrophosphination

Catalytic systems that are readily modifiable to achieve olefin migration or remote functionalization are highly sought-after in chemical synthesis. Here, we show that the combination of a commercially available nickel(II) pre-catalyst and a secondary phosphine oxide ligand enables site- and stereoselective alkene transposition for up to nine double-bond migrations within terminal and internal olefins under mild reductive conditions. Substrates bearing diverse functionalities including Brønsted acidic and reducible carbonyl groups are tolerated. Mechanistic and spectroscopic studies revealed the in situ generation of a catalytically active nickel-hydride species triggered by oxidative addition of the phosphine oxide. The reaction is amenable to regioconvergent isomerization as well as β-selective remote hydrophosphination when stoichiometric secondary phosphine oxide/base were employed.

Asymmetric Synthesis of P-Stereogenic Secondary Phosphine Oxides (SPOs)

P-stereogenic secondary phosphine oxides (SPOs, PHRR’(O)), valuable ligands for metal complexes in asymmetric catalysis, are also building blocks for other chiral phosphorus derivatives. This short review summarizes methods used for asymmetric synthesis of P-stereogenic SPOs.

Heterogeneous Catalytic Method for the Copper(II)-Catalysed Addition of H-Phosphinates and Secondary Phosphine Oxides to Phenylacetylene

Copper(II) on 4 Å molecular sieve was found to be an efficient heterogeneous catalyst in the addition of different H-phosphinates and secondary phosphine oxides to phenylacetylene. All hydrophosphinylation reactions were completely regioselective, as only β-isomers were formed, and the E-alkenylphosphinates and E-alkenylphosphine oxides were synthesized in moderate to excellent yields. The catalyst could be reused multiple times in the reaction. Graphic Abstract