A silver-free palladium-catalyzed dehydrogenative phosphorylation of terminal alkynes with hydrogen phosphine oxides has been developed. Both aromatic and aliphatic terminal alkynes including those bearing functional groups coupled readily with hydrogen phosphine oxides, producing the corresponding value-added alkynylphosphine oxides in good to excellent yields. This reaction could be easily conducted at gram scales (10 mmol) without any decrease of the reaction efficiency, showing highly potential synthetic value in organic synthesis. A plausible Pd(0)/Pd(II) mechanism is proposed.

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.

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.

An air-induced double addition of diphenyl phosphine oxide to various alkynes is reported. This reaction can proceed efficiently under metal- and solvent-free conditions, and is a clean and practically useful method for the preparation of the valuable 1,2-bisphosphorylethanes.

An air-induced double addition of diphenyl phosphine oxide to various alkynes is reported. This reaction can proceed efficiently under metal- and solvent-free conditions, and is a clean and practically useful method for the preparation of the valuable 1,2-bisphosphorylethanes.

A novel and efficient t-BuOK-mediated reductive addition of P(O)–H compounds to terminal alkynes was developed. A variety of β-arylphosphine oxides including the valuable β-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.

Trimethyl phosphine was used as an efficient catalyst for the addition of P(O)-H compounds to electron-deficient alkenes. The addition reactions were generally conducted using a catalytic amount of Me3P under mild reaction conditions. Both 1 to 1 and 1 to 2 adducts were obtained.Download high-res image (94KB)Download full-size image

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.

An efficient Ni-catalyzed synthesis of (E)-olefins using the readily available benzylic alcohol derivatives and arylacetonitriles is described. This transformation should proceed via a tandem process involving nickel-catalyzed cross coupling via C–O activation and subsequent stereoselective E2 elimination.

A novel Cu-catalysed substitution reaction of propargyl acetates with P(O)H compounds is developed to afford allenylphosphoryl compounds via C–P bond coupling in high yields under mild conditions. A plausible mechanism involving the nucleophilic interception of the Cu-allenylidene intermediates is proposed.

Because of the unique properties and wide applications, continuing efforts have been devoted to developing simpler and cleaner methods for the synthesis of organophosphorus compounds. Recently, transition metal-catalysed dehydrogenative coupling has been emerging as one of the powerful methodologies for constructing chemical bonds. Herein, we highlight the recent progress in the preparation of organophosphorus compounds via transition metal-catalysed dehydrogenative couplings of P(O)H compounds with Z–H compounds.

An efficient P–C bond-formation through iron-catalyzed cross coupling of P–H/C–O bonds is developed for the first time. This reaction proceeds efficiently to produce the corresponding valuable α-alkoxyphosphorus compounds under mild conditions with a wide generality.

•An efficient base-catalyzed (transition metal-free) double addition of H-phosphine oxides to alkynes is developed.•In the presence of a catalytic amount of t-BuOLi, various 1,2-bisphosphoryl compounds were produced in high yields.•This method provides an easy direct way to prepare bisphosphine oxides that are of high importance in organic synthesis.An efficient base-catalyzed double addition of H-phosphine oxides to alkynes is developed. In the presence of a catalytic amount of a base, the addition of various H-phosphine oxides to both aromatic and aliphatic alkynes took place efficiently to produce the corresponding bisphosphoryl compounds in excellent yields. This method provides an easy direct way to prepare bisphosphine oxides that are of high importance in organic synthesis.

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.

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.

The first Ni-catalyzed C–O/P–H cross-coupling producing organophosphorus compounds is disclosed. This method features wide generality in regard to both C–O and P–H compounds: for C–O compounds, the readily available alcohol derivatives of aryl, alkenyl, benzyl, and allyl are applicable, and for P–H compounds, both >PV(O)H compounds (secondary phosphine oxide, H-phosphinate, and H-phosphonate) and hydrogen phosphines (>PIIIH) can be used as the substrates. Thus, a variety of valuable C(sp2)–P and C(sp3)–P compounds can be readily obtained in good to excellent yields by this new strategy.

The Ni-catalyzed direct C–H/C–O cross couplings of benzylic alcohol derivatives with fluorobenzenes and heteroarenes are disclosed. This transformation provides a straightforward and efficient method for the synthesis of these valuable heteroatom-containing compounds.

Nickel-catalysed P–H/C–CN cross coupling reactions take place efficiently under mild reaction conditions affording the corresponding sp2C–P bonds. This transformation provides a convenient method for the preparation of arylphosphines and arylphosphine oxides from the readily available P–H compounds and arylnitriles.

The dehydrogenative coupling of terminal alkynes with secondary phosphine oxides is developed. In the presence of a silver additive, palladium acetate could efficiently catalyze the dehydrocoupling of secondary phosphine oxides with a variety of terminal alkynes to produce the corresponding alkynylphosphine oxides in high yields. A reaction mechanism is proposed.

P,C-Stereogenic 1,3-bisphosphinylpropanes 3 that have up to five stereogenic centers could be obtained stereoselectively in high yields by a one-step reaction of (RP)-menthylphenylphosphine oxide 1 with α,β-unsaturated aldehydes 2 catalyzed by KOH at room temperature. A mechanism was proposed as to involve a stereoselective intermolecular 1,3′-phosphorus migration from the 1,2-adduct of 1 with 2 to another 2 generating a 1,4-adduct that subsequently reacts with 1 to produce 3.

Chloroform-based Atherton–Todd-type reactions of alcohols and thiols with secondary phosphine oxides, generating phosphinothioates and phosphinates, respectively, are described. Various valuable phosphinothioates and phosphinates including those with functional groups are readily prepared under mild reaction conditions.

Under an oxygen atmosphere, the copper-mediated direct C3-cyanation of indole C–H bonds, using cheap and safe DMF as a CN source, took place selectively to produce the corresponding C3-cyanoindoles in good yields. A possible mechanism for this selective cyanation was proposed.Under an oxygen atmosphere, the copper-mediated direct C3-cyanation of indole C–H bonds, using cheap and safe DMF as a CN source, took place selectively to produce the corresponding C3-cyanoindoles in good yields. A possible mechanism for this selective cyanation was proposed.

A convenient and versatile method was developed for the preparation of 1,2-bisphosphorylethanes. Thus, in the presence of a catalytic amount of trimethylphosphine, a variety of >P(O)H compounds efficiently add to vinylphosphoryl compounds to produce the corresponding 1,2-bisphosphorylethanes in high yields. In most cases, the trimethylphosphine catalyst was simply removed under vacuum leaving spectroscopically pure adducts. The present method provided a halogen and metal-free clean process for the preparation of 1,2-bisphosphorylethanes.

The mechanism of the palladium-catalyzed cross dehydrogenative coupling of P(O)–H compounds with terminal alkynes was studied. Successive ligand-exchange reactions of Pd(OAc)2 with a hydrogen phosphoryl compound and a terminal alkyne take place readily to replace the two acetates on palladium, producing the corresponding (phosphoryl) (alkynyl)palladium complexes, which upon heating decomposed to the corresponding alkynylphosphorus compound. It is also confirmed that in the stoichiometric reactions of the complexes, the configuration at phosphorus is retained. On the basis of these stoichiometric reactions, an efficient synthesis of P-chiral alkynylphosphoryl compounds via palladium-catalyzed stereoselective cross dehydrogenative coupling of P-chiral P(O)–H compounds with terminal alkynes was developed. The key palladium complexes and the stereochemistry of the chiral phosphorus compounds are all unambiguously determined by single-crystal X-ray analysis.

An efficient one-pot synthesis of α-acyloxyphosphoryl compounds from aldehydes and hydrogen phosphoryl compounds has been developed using a facile base-mediated redox strategy. This redox transformation is applicable to synthesize a wide range of valuable α-acyloxyphosphoryl compounds with high atom- and step-economic efficiency.

•A rapid ligand exchange takes place by treating [(R2P)2O(CuOAc)2]2 with aqueous NH4Cl to generate [(R2P)2O(CuCl)2]2 in good yields.•The geometry of [(R2P)2O(CuCl)2]2 varies with the R group of the phosphorus units.•Whereas [(R2P)2O(CuOAc)2]2 is air sensitive, [(R2P)2O(CuCl)2]2 is stable under air.The reaction of secondary phosphine oxides R2P(O)H 1 with Cu(OAc)2 under nitrogen atmosphere produced complexes [(R2P)2O(CuOAc)2]22. A rapid ligand exchange took place when treating complexes 2 with NH4Cl to generate [(R2P)2O(CuCl)2]23 in good yields. The structures of 3 were determined by X-ray crystallography, showing that the geometries of these tetranuclear copper complexes vary with the R group of the phosphorus units. Compared to complexes 2 which are air sensitive, complexes 3 are stable under air.The reaction of secondary phosphine oxides R2P(O)H 1 with Cu(OAc)2 under nitrogen atmosphere produced complexes [(R2P)2O(CuOAc)2]22. A rapid ligand exchange took place when treating complexes 2 with NH4Cl to generate [(R2P)2O(CuCl)2]23 in good yields. The structures of 3 were determined by X-ray crystallography, showing that the geometries of these tetranuclear copper complexes vary with the R group of the phosphorus units. Compared to complexes 2 which are air sensitive, complexes 3 are stable under air.

A Brønsted acid Ph2P(O)OH can efficiently catalyze the reaction of a Pd(0) complex with an alkyne to produce a novel alkenyl(alkynyl)palladium complex via selective hydropalladation and ligand exchange processes. On the basis of this finding, an efficient Pd(0)/Ph2P(O)OH mediated head-to-tail dimerization of alkynes was disclosed.

Trimethylphosphine efficiently catalyzed the dimerization reaction of vinylphosphorus compounds to selectively afford the linear non-branched tail-to-tail β,β-dimerization dimers via umpolung of the substrates.

A facile, highly stereo- and regioselective hydrometalation of alkynes generating alkenylmetal complex is disclosed for the first time from a reaction of alkyne, carboxylic acid, and a zerovalent group 10 transition metal complex M(PEt3)4 (M = Ni, Pd, Pt). A mechanistic study showed that the hydrometalation does not proceed via the reaction of alkyne with a hydridometal generated by the protonation of a carboxylic acid with Pt(PEt3)4, but proceeds via a reaction of an alkyne coordinate metal complex with the acid. This finding clarifies the long proposed reaction mechanism that operates via the generation of an alkenylpalladium intermediate and subsequent transformation of this complex in a variety of reactions catalyzed by a combination of Brϕnsted acid and Pd(0) complex. This finding also leads to the disclosure of an unprecedented reduction of alkynes with formic acid that can selectively produce cis-, trans-alkenes and alkanes by slightly tuning the conditions.

A new oxapalladacycle 3 can be conveniently prepared via direct ortho palladation of diphenylphosphinic acid with palladium acetate. Catalysts derived from 3 can efficiently catalyze Markovnikov-type additions of E–H bonds (P(O)–H, S–H and spC–H) to alkynesvia a unique catalytic cycle.

The reaction of H-phosphinates and secondary phosphine oxides with amines and alcohols proceeds highly stereospecifically to give the corresponding coupling products with inversion of configuration at the phosphorus center under the Atherton−Todd reaction conditions. This finding leads to the establishment of a general and efficient method for the synthesis of a variety of optically active organophosphorus acid derivatives from the easily available chiral H-phosphinates and secondary phosphine oxides.

A general and efficient method for the preparation of optically active Z1Z2P(O)Cl from the easily prepared optically active H-phosphinates and H-phosphine oxides was reported. H-Phosphinates and H-phosphine oxides react stereospecifically with CuCl2 to produce the corresponding optically active Z1Z2P(O)Cl with retention of configuration at the phosphorus center. Optically active Z1Z2P(O)Cl reacts easily with a variety of nucleophiles to produce other chiral organophosphorus acid derivatives with inversion of configuration at phosphorus.

Copper catalyzed the aerobic oxidative coupling of terminal alkynes with H-phosphonates to afford alkynylphosphonates in high yields.

An efficient oxygen–phosphoryl bond-forming reaction via iron-catalyzed cross dehydrogenative coupling has been developed. This transformation proceeds efficiently under oxidant- and halide-free reaction conditions with H2 liberation, and represents a straightforward method to prepare valuable organophosphoryl compounds from the readily available alcohols and P(O)–H compounds.

The first nickel-catalyzed phosphinylation of C–S bonds forming C–P bonds is developed. This transformation can proceed readily with the simple Ni(cod)2 at a loading down to 0.1 mol% at the 10 mmol scale. A variety of aryl sulfur compounds, i.e. sulfides, sulfoxides and sulfones all couple with P(O)–H compounds to produce the corresponding organophosphorus compounds in high yields, which provides an efficient new method for the construction of C–P bonds.

A novel CuI-catalyzed cross-coupling of propargyl epoxides with P(O)H compounds is disclosed. The reaction proceeded efficiently under mild conditions to give 4-phosphoryl 2,3-allenols in good to high yields with excellent selectivity. The utility of the products was demonstrated and a plausible mechanism was also proposed.

A novel and efficient t-BuOK-mediated reductive addition of P(O)–H compounds to terminal alkynes was developed. A variety of β-arylphosphine oxides including the valuable β-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.

An efficient Ni-catalyzed synthesis of (E)-olefins using the readily available benzylic alcohol derivatives and arylacetonitriles is described. This transformation should proceed via a tandem process involving nickel-catalyzed cross coupling via C–O activation and subsequent stereoselective E2 elimination.

A novel Cu-catalysed substitution reaction of propargyl acetates with P(O)H compounds is developed to afford allenylphosphoryl compounds via C–P bond coupling in high yields under mild conditions. A plausible mechanism involving the nucleophilic interception of the Cu-allenylidene intermediates is proposed.

Nickel-catalysed P–H/C–CN cross coupling reactions take place efficiently under mild reaction conditions affording the corresponding sp2C–P bonds. This transformation provides a convenient method for the preparation of arylphosphines and arylphosphine oxides from the readily available P–H compounds and arylnitriles.

A Brønsted acid Ph2P(O)OH can efficiently catalyze the reaction of a Pd(0) complex with an alkyne to produce a novel alkenyl(alkynyl)palladium complex via selective hydropalladation and ligand exchange processes. On the basis of this finding, an efficient Pd(0)/Ph2P(O)OH mediated head-to-tail dimerization of alkynes was disclosed.

Because of the unique properties and wide applications, continuing efforts have been devoted to developing simpler and cleaner methods for the synthesis of organophosphorus compounds. Recently, transition metal-catalysed dehydrogenative coupling has been emerging as one of the powerful methodologies for constructing chemical bonds. Herein, we highlight the recent progress in the preparation of organophosphorus compounds via transition metal-catalysed dehydrogenative couplings of P(O)H compounds with Z–H compounds.

An efficient P–C bond-formation through iron-catalyzed cross coupling of P–H/C–O bonds is developed for the first time. This reaction proceeds efficiently to produce the corresponding valuable α-alkoxyphosphorus compounds under mild conditions with a wide generality.

A new oxapalladacycle 3 can be conveniently prepared via direct ortho palladation of diphenylphosphinic acid with palladium acetate. Catalysts derived from 3 can efficiently catalyze Markovnikov-type additions of E–H bonds (P(O)–H, S–H and spC–H) to alkynesvia a unique catalytic cycle.

The dehydrogenative coupling of terminal alkynes with secondary phosphine oxides is developed. In the presence of a silver additive, palladium acetate could efficiently catalyze the dehydrocoupling of secondary phosphine oxides with a variety of terminal alkynes to produce the corresponding alkynylphosphine oxides in high yields. A reaction mechanism is proposed.