13468-89-8

Upstream product

• 824-72-6 P,P-dichlorophenylphosphine oxide 
• 107-21-1 ethylene glycol 
• 1006-83-3 2-phenyl-[1,3,2]dioxaphospholane 
• 936-51-6 2-phenyl-1,3-dioxolane 
• 58816-54-9 1-(methoxy-phenyl-phosphinoyl)-5-phenyl-1H-pyrazole-3-carboxylic acid methyl ester 
• 1571-33-1 phenylphosphonate 
• 4129-17-3 diphenylphosphoranyl azide 
• 644-97-3 Dichlorophenylphosphine 
• 78133-06-9 C₁₄H₁₆NO₃P 
• 34736-73-7 5-phenyl-1,4,6,9-tetraoxa-5-phosphaspiro<4.4>nonane 
• 58816-57-2 O-Methyl-O-β-hydroxyaethyl-phenylphosphonat 
• 59259-22-2 bis(2-hydroxyethyl) phenylphosphonate 
• 75-21-8 oxirane 
• 55861-16-0 phenyl dioxophosphorane 

Downstream Products

• 10311-08-7 dimethyl(phenyl)phosphine oxide 

Relevant academic research and scientific papers

Direct conversion of phosphonates to phosphine oxides: An improved synthetic route to phosphines including the first synthesis of methyl JohnPhos

The synthesis of tertiary phosphine oxides from phosphonates was achieved reliably and in good to excellent yields using stoichiometric amounts of alkyl or aryl Grignard reagents and sodium trifluoromethanesulfonate (NaOTf). In the absence of the NaOTf additive, covalent coordination oligomers of magnesium and phosphorus species dominate the reaction, producing very low yields of phosphine oxide, but high conversions of the phosphonate starting material. Mechanistic studies revealed that a five-coordinate phosphorus species - not a phosphinate - is the reaction intermediate. A diverse array of phosphonates was converted to phosphine oxides using a variety of Grignard reagents for direct carbon-phosphorus functionalization. This new methodology especially simplifies the synthesis of dimethylphosphino (RPMe2)-type phosphines by using air-, water-, and silica-stable intermediates. To highlight this reaction, a new Buchwald-type ligand ([1,1′-biphenyl]-2-yldimethylphosphine, or methyl JohnPhos) and a classic bidentate phosphine, bis(diphenylphosphino)propane (dppp), were synthesized in excellent yields.

Part I: The development of the catalytic wittig reaction

We have developed the first catalytic (in phosphane) Wittig reaction (CWR). The utilization of an organosilane was pivotal for success as it allowed for the chemoselective reduction of a phosphane oxide. Protocol optimization evaluated the phosphane oxide precatalyst structure, loading, organosilane, temperature, solvent, and base. These studies demonstrated that to maintain viable catalytic performance it was necessary to employ cyclic phosphane oxide precatalysts of type 1. Initial substrate studies utilized sodium carbonate as a base, and further experimentation identified N,N-diisopropylethylamine (DIPEA) as a soluble alternative. The use of DIPEA improved the ease of use, broadened the substrate scope, and decreased the precatalyst loading. The optimized protocols were compatible with alkyl, aryl, and heterocyclic (furyl, indolyl, pyridyl, pyrrolyl, and thienyl) aldehydes to produce both di- and trisubstituted olefins in moderate-to-high yields (60-96 %) by using a precatalyst loading of 4-10 mol %. Kinetic E/Z selectivity was generally 66:34; complete E selectivity for disubstituted α,β-unsaturated products was achieved through a phosphane-mediated isomerization event. The CWR was applied to the synthesis of 54, a known precursor to the anti-Alzheimer drug donepezil hydrochloride, on a multigram scale (12.2 g, 74 % yield). In addition, to our knowledge, the described CWR is the only transition-/heavy-metal-free catalytic olefination process, excluding proton-catalyzed elimination reactions. A point of difference: By utilizing an organosilane to chemoselectively reduce a phosphane oxide precatalyst to a phosphane (see scheme), the first catalytic (in phosphane) Wittig reaction has been developed. The methodology has been applied to the synthesis of 22 disubstituted and 24 trisubstituted olefins, including a multigram synthesis of a precursor to the anti-Alzheimer drug donepezil hydrochloride.

Conversions of 2-phenyl-1,3,2-dioxaphospholane under the action of hydrogen chloride

The reaction of 2-phenyl-1,3,2-dioxaphospholane with HCl gives a mixture of phenylphosphinic acid, bis(2-chloroethyl) phenylphosphonate, and phenylphosphine; therewith, intermediate oligomeric phosphonites, hydrophosphoryl compounds, and phosphoranes were detected. Thermal treatment of the reaction mixture results in formation of ethylene phenylphosphonate and (2-chloroethyl)phenylphosphinate.

Reaction of dichlorophosphines with glycidol. New data on the transformations of cyclic phosphonates

Reaction of dichlorophosphines with glycidol yields 2-R-4-chloromethyl-1,3,2-dioxaphospholanes as primary products, which under the reaction conditions or under the action of HC1 surprisingly readily undergo redox transformations yielding 2-R-4-chloromethyl-1,3,2-dioxaphospholane 2-oxides, dichloropropyl R-phosphinates, bis(dichloropropyl) R-phosphonates, and phosphines RPH2.

Simple method for cleavage of phosphonic acid diesters to monoesters

Phosphonic acid dialkyl or diaryl esters give, on treatment with alkali azide or alkali iodide in DMF at 100°C, quantitatively and specifically the corresponding monoesters. The reaction is applied in a series of acyclic nucleotide analogs for the preparation of PMEA monoesters and related compounds.

Kinetics and mechanism of the hydrolysis of a (5,6)-spirophosphorane. Thermodynamics of the hydrolysis of cyclic five-membered and six-membered phosphonium ions

The cyclic five-membered phosphonium ion 2b (2-(2'-hydroxyethoxy)-2-phenyl-1,3,2-dioxaphospholan-2-ylium) derived from ring opening of the (5,5)-spirophosphorane 1b (5-phenyl-1,4,6,9-tetraoxa-5-phosphaspirononane) has been observed in neat CF3SO3H and at >85percent H2SO4.The cation undergoes hydrolysis in the latter solutions, and an extrapolation has been carried out to obtain an estimate for reactivity in 100percent water.Hydrolysis rate constants for phenyltrialkoxyphosphonium ions in water are 107, 100, and 5*10-3 s-1 for cyclic five-membered, cyclic six-membered, and acyclic derivatives re spectively; these show an excellent correlation with rate constants for a similar series of phosphate esters.An investigation of the hydrolysis of the (5,6)-spirophosphorane 5 (5-phenyl-8,8-dimethyl-1,4,6,10-tetraoxa-5-phosphaspirodecane) provides a clue as to the origins of these rate differences.This phosphorane can in principle hydrolyze via two isomeric cyclic phosphonium ions, the six-membered 14 and the five-membered 15.The former is thermodynamically more stable, being the only cation observed under equilibrating conditions of strong acid.However, the hydrolysis of the spirophosphorane, as well as the hydrolysis of fully formed 14, channels through the cyclic five-membered 15.A thermodynamic breakdown reveals that the 9.5 kcal mol-1 difference in activation free energy for the hydrolysis of five- and six-membered cyclic phosphonium ions is due to a combination of a higher free energy (2.5-4.5 kcal mol-1) for the five membered cation, and a lower free energy (7-5 kcal mol-1) for the pentacoordinate transition state with the five membered ring.This analysis also shows that a (5,6)-spirophosphorane is 6-8 kcal mol-1 more stable than a (6,6)-spirophosphorane.Thus, a five-membered ring has a significant stabilizing effect on a pentacoordinated phosphorus structure.The accelerated hydrolysis of cyclic phosphonium ions and phosphate esters with five-membered rings is caused by combination of this stabilizing effect in the transition state and a destabilizing effect in the ground state associated with ring strain. Key words: phosphorane, hydrolysis, phosphate, phosphonium.

Contribution of Ring Strain and the Stereoelectronic Effect of the Hydrolysis of Cyclic Five-Membered Ring Phosphorus Esters

The rate of base catalyzed hydrolysis of cyclic five-membered ring 2-oxo-2-phenyl-1,2-oxaphospholan, 1, and 2-oxo-2-phenyl-1,3,2-dioxaphospholan, 2, and their acyclic analogues ethyl ethylphenylphosphinate, 3, and diethyl phenylphosphonate, 4, were measur

Hydrolysis of Spirobicyclic Oxophosphoranes. Associative and Dissociative Reactions

The hydrolysis reactions of three aryl-substituted spirobicyclic oxyphosphoranes (Ia-c) have been studied in aqueous solution.These are characterized by an H+-catalyzed reaction extending to about pH 9.54 sharply changing there to an OH--catalyzed reaction.The acid reaction is general acid catalyzed (α=0.74) and appears to be a dissociative process directly analogous to the general acid catalyzed hydrolysis of an acetal or ortho ester.Features indicative of this type of reaction include a negative ρ value based on the variation of the aromatic substituent, a near-zero entropy of activation, and a slightly inverse solvent isotope effect.The hydroxide ion reaction appears to be an associative process proceeding through a hexacoordinated phosphoroxanide ion.Evidence for this includes a positive ρ value (+2.5) and a significantly negative entropy of activation.General base catalysis is also observed; this also appears to be an associative process on the basis of a positive ρ value.

PHOTOLYTIC REARRANGEMENT OF PHOSPHORUS AZIDE : EVIDENCE FOR A TRANSIENT METAPHOSPHONIMIDATE.

Photolysis of the oxide of diphenylphosphine azide gives rise to a transient metaphisphonimidate, a new tricoordinated pentavalent phosphorus compound.Evidence for this species was given by trapping reactions on a variety of substrates.