Beyond Triphenylphosphine: Advances on the Utilization of Triphenylphosphine Oxide.

Triphenylphosphine oxide is a well-known industrial waste byproduct, and thousands of tons of it are generated every year. Due to its chemical stability and limited applications, settlement of this waste issue has drawn extensive attention from chemists. The reduction of triphenylphosphine oxide to triphenylphosphine is heretofore the most employed solution, and is well reviewed. In view of our recent studies on the selective and efficient conversion of Ph3P(O) to other valuable organophosphorus chemicals by using sodium, the present perspective mainly highlights the advances on the utilization of Ph3P(O) to prepare a diverse range of functional organophosphorus compounds, except Ph3P, via selective P-C, C-H, and P-O bond cleavages.

Reductive Coupling of P(O)-H Compounds and Aldehydes for the General Synthesis of Phosphines and Phosphine Oxides.

A novel strategy for the selective construction of a C(sp3)-P(III) or -P(V) bond from >P(O)-H compounds and aldehydes is disclosed. By using the H3PO3/I2 system, various secondary phosphine oxides could react with both aromatic and aliphatic aldehydes to afford valuable phosphines (isolated as sulfides) and phosphine oxides in good yields. This method features a wide substrate scope and simple reaction conditions and avoids the use of toxic halides and metals.

Ligand-Free Iron-Catalyzed Construction of C-P Bonds via Phosphorylation of Alcohols: Synthesis of Phosphine Oxides and Phosphine Compounds.

An efficient method for the construction of C-P(V) and C-P(III) bonds via the iron-catalyzed phosphorylation of alcohols under ligand-free conditions is disclosed. This strategy represents a straightforward process to prepare a series of phosphine oxides and phosphine compounds in good to excellent yields from the readily available alcohols and P-H compounds. A plausible mechanism is also proposed. We anticipate that this mode of transforming simple alcohols would apply in chemical synthesis widely.

Reduction of Triphenylphosphine Oxide to Triphenylphosphine by Phosphonic Acid.

A novel method for the iodine-mediated reduction of phosphine oxides (sulfides) to phosphines using phosphonic acid under solvent-free conditions is described. By using a combination of H3PO3 and I2, both tertiary monophosphine oxides and bis-phosphine oxides were reduced under this system, readily producing monodentate and bidentate phosphines, respectively, in good yields. Notably, chiral (R)-(+)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl dioxide could be also tolerated without racemization. This new approach is inexpensive and features simple conditions and a wide substrate scope.

Conversion of Aryl Aldehydes to Benzyl Iodides and Diarylmethanes by H3PO3/I2.

For the first time, H3PO3 was used as both the reducing reagent and the promotor in the reductive benzylation reactions with aryl aldehydes. By using a H3PO3/I2 combination, various aromatic aldehydes underwent iodination reactions and Friedel-Crafts type reactions with arenes via benzyl iodide intermediates, readily producing benzyl iodides and diarylmethanes in good yields. Intramolecular cyclization reactions also took place, giving the corresponding cyclic compounds. This new strategy features easy-handling, low-cost, and metal-free conditions.

Three-Component Reactions of α-Amino Acids, p-Quinone Monoacetals, and Diarylphosphine Oxides to Selectively Afford 3-(Diarylphosphinyl)anilides and N-Aryl-2-diarylphosphinylpyrrolidines.

The three-component reactions of α-amino acids, p-quinone monoacetals (or p-quinol ethers), and diarylphosphine oxides have been developed for the synthesis of 3-(diarylphosphinyl) anilides and N-aryl-2-diarylphosphinylpyrrolidines. The transformations may involve the in situ generation of conjugated azomethine ylides or 2-azaallyl anion species from the reaction of α-amino acids and p-quinone monoacetals, which are further trapped by diarylphosphine oxides.

Selective C-P(O) Bond Cleavage of Organophosphine Oxides by Sodium.

Sodium exhibits better efficacy and selectivity than Li and K for converting Ph3P(O) to Ph2P(OM). The destiny of PhNa co-generated is disclosed. A series of alkyl halides R4X and aryl halides ArX all react with Ph2P(ONa) to produce the corresponding phosphine oxides in good to excellent yields.

Wet and Dry Processes for the Selective Transformation of Phosphonates to Phosphonic Acids Catalyzed by Brønsted Acids.

A "wet" process and two "dry" processes for converting phosphonate esters to phosphonic acids catalyzed by a Brønsted acid have been developed. Thus, in the presence of water, a range of alkyl-, alkenyl-, and aryl-substituted phosphonates can be generally hydrolyzed to the corresponding phosphonic acids in good yields catalyzed by trifluoromethyl sulfonic acid (TfOH) at 140 °C (the wet process). On the other hand, with specific substituents of the phosphonate esters, the conversion to the corresponding phosphonic acids can be achieved under milder conditions in the absence of water (the dry process). Thus, the conversion of dibenzyl phosphonates to the corresponding phosphonic acids took place smoothly at 80 °C in toluene or benzene in high yields. Moreover, selective conversion of benzyl phosphonates RP(O)(OR')(OBn) to the corresponding mono phosphonic acids RP(O)(OR')(OH) can also be achieved under the reaction conditions. The dealkylation via the generation of isobutene of di-tert-butyl phosphonate, and the related catalysis by TfOH took place even at room temperature to give the corresponding phosphonic acids in good to high yields. Nafion also shows high catalytic activity for these reactions. By using Nafion as the catalyst, phosphonic acids could be easily prepared on a large scale via a simple process.

Zinc-catalyzed regioselective C-P coupling of p-quinol ethers with secondary phosphine oxides to afford 2-phosphinylphenols.

The zinc triflate-catalyzed highly regioselective C-P cross coupling reaction of p-quinol ethers with secondary phosphine oxides is reported. The reaction provides a facile alternative method for the synthesis of 2-phosphinylphenols in good to high yields. Mechanistically, zinc triflate may serve as an oxophilic σ-Lewis acid to activate the C-O bond in p-quinol ether first. Then the regioselective attack of the phosphorus nucleophile at the α-carbon position takes place to form the C-P bond and give the product. In addition, α-alkynyl substituted p-quinol ethers also react with secondary phosphine oxides in the same reaction mode to give 6-alkynyl 2-phosphinylphenols in the presence of the zinc catalyst.

Hydrophosphorylation of Alkynes Catalyzed by Palladium: Generality and Mechanism.

We carried out a comprehensive study on the generality, scope, limitations, and mechanism of the palladium-catalyzed hydrophosphorylation of alkynes with P(O)-H compounds (i.e., H-phosphonates, H-phosphinates, secondary phosphine oxides, and hypophosphinic acid). For H-phosphonates, Pd/dppp was the best catalyst. Both aromatic and aliphatic alkynes, with a variety of functional groups, were applicable to produce the Markovnikov adducts in high yields with high regioselectivity. Aromatic alkynes showed higher reactivity than aliphatic alkynes. Terminal alkynes reacted faster than internal alkynes. Sterically crowded H-phosphonates disfavored the addition. For H-phosphinates and secondary phosphine oxides, Pd/dppe/Ph2P(O)OH was the catalyst of choice, which led to highly regioselective formation of the Markovnikov adducts. By using Pd(PPh3)4 as the catalyst, hypophosphinic acid added to terminal alkynes to give the corresponding Markovnikov adducts. Phosphinic acids, phosphonic acid, and its monoester were not applicable to this palladium-catalyzed hydrophosphorylation. Mechanistic studies showed that, with a terminal alkyne, (RO)2P(O)H reacted, like a Brønsted acid, to selectively generate the α-alkenylpalladium intermediate via hydropalladation. On the other hand, Ph(RO)P(O)H and Ph2P(O)H gave a mixture of α- and ß-alkenylpalladium complexes. In the presence of Ph2P(O)OH, hydropalladation with this acid took place first to selectively generate the α-alkenylpalladium intermediate. A subsequent ligand exchange with a P(O)H compound gave the phosphorylpalladium intermediate which produced the Markovnikov adduct via reductive elimination. Related intermediates in the catalytic cycle were isolated and characterized.

Oxidative Dephosphorylation of Benzylic Phosphonates with Dioxygen Generating Symmetrical trans-Stilbenes.

Under a dioxygen atmosphere, benzylphosphonates and related phosphoryl compounds can readily produce the corresponding trans-stilbenes in high yields with high selectivity upon treatment with bases. Various functional groups were tolerable under the reaction conditions.

Transition-Metal-Free C-P Bond Formation via Decarboxylative Phosphorylation of Cinnamic Acids with P(O)H Compounds.

A novel, transition-metal-free phosphorylation of cinnamic acids with P(O)H compounds has been developed via radical-promoted decarboxylation under mild conditions. This method provides simple, efficient, and versatile access to valuable ( E)-alkenylphosphine oxides in satisfactory yields with a wide variety of substrates.

Radical Hydrophosphorylation of Alkynes with R2P(O)H Generating Alkenylphosphine Oxides: Scope and Limitations.

Radical hydrophosphorylation of aliphatic terminal alkynes with H-phosphine oxides can produce the corresponding anti-Markovnikov alkenylphosphorus adducts in moderate yields. This method is a cleaner approach for the preparation of the corresponding alkenylphosphine oxides, since it avoids the use of a metal catalyst that sometimes is difficult to remove from the products.

Direct C-OH/P(O)-H dehydration coupling forming phosphine oxides.

A t-BuONa-mediated C-OH/P(O)-H cross dehydration coupling to produce alkylphosphine oxides is developed. This reaction employed readily available alcohols and P(O)-H compounds as the starting materials, providing an efficient alternative method for constructing sp3 C-P bonds. A reasonable reaction path involving dehydration and subsequent regio-selective hydrophosphorylation of the resulting alkenes was proposed.

Reinvestigation of the Substitutions Reaction of Stereogenic Phosphoryl Compounds: Stereochemistry, Mechanism, and Applications.

Nucleophilic substitutions at P centers are of high importance in biological processes and asymmetric synthesis. However, detailed studies on this topic are rare. P-Stereogenic compounds containing P-Cl, P-O, and P-S bonds were diastereoselectively prepared and then used to study the substitution of Cl, O, and S at phosphorus centers with organometallic reagents. It was proposed that with alkynyl metallic reagents an SN2-like mechanism (route A1) and a Berry pseudorotation (BPR) of pentacoordinated phosphorus intermediates (route B1) were involved and afforded P-inverted and P-retained products, respectively. The P-inverted conversion of a P-Cl functionality to a P-C functionality can be controlled by either the temperature or the order of addition of the starting materials. The introduction of a P-Cl bond using an alkyl metallic reagent proceeded through routes A2 and A2'. At higher temperatures, P-inverted products were predominantly afforded via SN2-like route A2. At lower temperatures, bis-substituted products were formed via route A2' and cleavage of the P-O bond. The P-S bonds were accompanied by the epimerization of the starting materials, triggered by the alkylthio anion, via route C. The epimerization can be suppressed by the use of a poorly soluble magnesium alkylthiolate, and the P-retained compounds will be formed as the major products via route B3 and BPR of the intermediates.

t-BuOK-mediated reductive addition of P(O)-H compounds to terminal alkynes forming ß-arylphosphine oxides.

A novel and efficient t-BuOK-mediated reductive addition of P(O)-H compounds to terminal alkynes was developed. A variety of ß-arylphosphine oxides including the valuable ß-heteroarylphosphine oxides were produced in moderate to high yields under mild reaction conditions. This reaction may proceed via a tandem process involving regio-selective double addition and subsequent transfer hydrogenation.

Efficient Pd-Catalyzed Dehydrogenative Coupling of P(O)H with RSH: A Precise Construction of P(O)-S Bonds.

A Pd-catalyzed dehydrogenative phosphorylation of thiols is developed. A variety of thiols dehydrogenatively couple readily with all three kinds of P(O)-H compounds, i.e., H-phosphonates, H-phosphinates, and secondary phosphine oxides, providing a general access to the valuable phosphorothioates including the P-chiral compounds. A plausible mechanism is proposed.

Rhodium- and Iridium-Catalyzed Asymmetric Addition of Optically Pure P-Chiral H-Phosphinates to Aldehydes Leading to Optically Active α-Hydroxyphosphinates.

Optically active α-hydroxyphosphinates with both C- and P-stereogenic centers are obtained by rhodium- or iridium-catalyzed substrate-directed stereoselective addition of the optically pure H-phosphinates to aldehydes. The reaction most probably proceeds by a transition-metal-catalyzed mechanism with hydridometal complexes as key intermediates in the catalytic cycle.

Nickel-Catalyzed Phosphorylation of Phenol Derivatives via C-O/P-H Cross-Coupling.

An efficient nickel-catalyzed phosphorylation of phenol derivatives with P(O)-H compounds via C-O/P-H cross-coupling is described. Under the reaction conditions, various phenyl pivalates coupled readily with hydrogen phosphoryl compounds to afford the corresponding coupling products aryl phosphonates and aryl phosphine oxides in good to high yields.

Stereospecific Preparations of P-Stereogenic Phosphonothioates and Phosphonoselenoates.

P-Stereogenic phosphonothioates and phosphonoselenoates were readily prepared utilizing RP-menthyl phenylphosphite 1 by two methods. The first method used elemental sulfur or selenium to react with 1, followed by alkylation of the intermediates with alkyl halides. The second used 1 to react with disulfide or diselenide. Both methods stereospecifically produced the title compounds in nearly quantitative yields under mild conditions. Stereospecific chalcogenation of the phosphoryl was proposed as the key step in these reactions.