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Several approaches were developed for the preparation of phosphorus-substituted 5- and 6-membered benzophostams. Carbodiimide-promoted cyclization of zwitterionic aminophosphinates derived from a nitrobenzene precursor accomplished the cyclization in good yields. Alternatively, a novel copper-catalyzed cross-coupling between a phosphonamide and a bromobenzene precursor produced the heterocycles in moderate to good yields. Three different methods are compared for the synthesis of the P-ethoxy-substituted 5-membered benzophostam.

Thiophosphorus acids R1R2P(S)OH constitute an important class of organophosphorus compounds, in which the phosphorus atom is intrinsically chiral if R1 ≠ R2. In connection with a project aimed at the preparation of chiral thiophosphorus acids, various available literature methods were considered, but few fit the requirement of odorless reagents. Herein, the results of our studies on the synthesis of thiophosphinic acids are reported. Ultimately, two major approaches were selected: (1) the Stec reaction of phosphorus amides with carbon disulfide; and (2) the one-pot synthesis of thiophosphorus acids from H-phosphinates, an organometallic nucleophile, and quenching with elemental sulfur. An application to the preparation of a potential chiral phosphorus organocatalyst is also reported.

Several approaches were developed for the preparation of phosphorus-substituted 5- and 6-membered benzophostams. Carbodiimide-promoted cyclization of zwitterionic aminophosphinates derived from a nitrobenzene precursor accomplished the cyclization in good yields. Alternatively, a novel copper-catalyzed cross-coupling between a phosphonamide and a bromobenzene precursor produced the heterocycles in moderate to good yields. Three different methods are compared for the synthesis of the

International audience; Ei-ichi Negishi will remain known for pioneering and promoting the development of transition-metal catalyzed reactions in organic synthesis as well as fostering excellence and critical thinking among his collaborators. During his lifetime, with his wife Sumire by his side, he conquered many continents: in the chemical world, his name is associated with cross-coupling, cascade reactions, carbopalladation, zirconocene chemistry, and asymmetric synthesis; in life, we remember him as a kind, generous, and approachable individual that mastered golfing, singing, and skiing, among other things.

The free-radical arylation of H-phosphinates and related compounds was examined. A practical catalytic process with the air as the oxidant could not be found. However, an inexpensive and robust methodology was developed, using catalytic Mn(II) as the radical initiator and excess Mn(IV) as the stoichiometric oxidant. Using these conditions, the inter- and intramolecular arylation of phosphinylidene compounds has a broad scope, including application to the synthesis of P-heterocycles. A full account of this methodology is presented including a discussion of its limitations.

The cost of reagents and catalysts employed in synthetic methodologies developed in academia is very rarely discussed. Yet these costs are very real as they represent a significant portion of any grant proposal budget. Herein, we wish to introduce the concept of Cost of Academic Methodologies (CAM) as an aspect, which should be considered when evaluating synthetic methodologies. We also introduce an associated concept: the Aggregate Molecular Weight (AMW). In order to illustrate these concepts, examples from various laboratories, including our own, are evaluated through the CAM/AMW lens.

Several major challenges still remain in organophosphorus chemistry. Organophosphorus compounds are currently synthesized from phosphorus trichloride (PCl3), even though the final consumer products (such as pesticides, flame-retardants, extractants) do not contain reactive phosphorus-chlorine bonds. In order to bypass phosphorus trichloride, significant interest has been devoted to functionalizing elemental phosphorus (P4, the precursor to PCl3), red phosphorus (Pred), or phosphine (PH3). Yet, phosphinates (ROP(O)H2) are already available on an industrial scale and are the most environmentally benign, but their use as phosphorus trichloride replacements has been completely overlooked until a few years ago. An overview of some of the methodologies developed in my laboratory for P–C and P–O bond-forming reactions through phosphinate chemistry, as well as some selected applications, are presented. Another significant challenge remains the synthesis of P-stereogenic compounds. My group’s recent progress in this area is also discussed. Based on menthol as an inexpensive chiral auxiliary, various menthyl phosphinates can be synthesized. These phosphinates are precursor to P-stereogenic phosphines through well-established literature transformations.

Carbon-phosphorus (C−P) bond-forming reactions via homolytic aromatic substitution (HAS) of non-functionalized substrates with phosphinylidene P(O)H compounds is becoming a useful synthetic tool for the preparation of aryl and heteroaryl phosphonates, phosphinates, and phosphine oxides. This review specifically covers recent work using manganese-mediated free radical processes. Several research groups employ expensive Mn(OAc)3, whereas our own contributions focus on the novel and inexpensive Mn(OAc)2/MnO2 system.

Easily prepared menthyl phosphinates of high diastereoisomeric purity provide versatile intermediates for the synthesis of P-stereogenic compounds. Previous efforts starting about fifty years ago have been hampered by a lack of generality so the menthyl route has been nearly abandoned. Herein we provide a general solution to this long-standing problem and describe a general synthesis of menthyl H-phosphinate and disubstituted phosphinate esters. The method to prepare these versatile precursors relies on a simple and inexpensive process avoiding the use of phosphorus trichloride, Grignard reagents, and complicated cryogenic crystallizations. Established protocols can then be employed to synthesize P-stereogenic secondary and tertiary phosphine oxides and therefore P-stereogenic phosphine ligands.

Pyrophosphate analogues are of great importance especially for the design of biologically active molecules. The phospha-Claisen condensation allows for the rapid synthesis of (phosphonomethyl)phosphinate pyrophosphate analogues and building blocks that can be employed in numerous applications.

Manganese catalyzed reactions of H-phosphinates with various alkenes give the corresponding alkylated products.

Literature published between 2008 and 2013 concerning the functionalization of carbon–hydrogen into carbon–phosphorus bonds is surveyed. The chapter is organized by reaction mechanism. The majority of methods still proceed via deprotonation of C–H into C–M (M=Li, Na, etc.) followed by reaction with a phosphorus electrophile P–X, where X is usually chlorine. A few examples of electrophilic aromatic substitution and related processes have also been reported, although this approach has not yet been developed significantly. Over the past 5 years a rapidly growing family of reactions includes transition metal “C–H activation” and formally related radical-based processes has been developed. The latter processes offer exciting prospects for the synthesis of organophosphorus compounds.

The Mn(II)/Mn(IV) system was used to achieve the bisfunctionalization of alkenes with phosphorus and chlorine in moderate to good yields. A variety of phosphinylidene-containing (P(O)H) compounds were examined. When the phosphorus reagent is limiting, the reaction yield is generally in the 40–50% range, although the structure of the organophosphorus starting material greatly influences it. The reaction is simple and inexpensive and the β-chloro-phosphinoyl products are versatile intermediates. For example, elimination with DBU gave the corresponding α,β-unsaturated phosphorus compound stereoselectively.

A new family of chiral auxiliaries designed on a conformationally restricted version of (-)-8-phenylmenthol has been developed. Both enantiomers are available from an inexpensive synthesis conducted on multigram scale. A first application has showed comparable diastereoselectivity between the novel auxiliary and (-)-8-phenylmenthol.

A process for the conversion of hypophosphorous acid (H3PO2, HPA) and alcohols into various H-phosphonate diesters [(RO)2P(O)H] is described. The new reaction provides a missing bridge between HPA and important H-phosphonates, completely avoiding the use of PCl3. Nickel chloride or nickel on silica catalyze the oxidative phosphorylation of alkyl phosphinates with various alcohols or water. The reaction is atom economic and avoids the formation of waste products. The previous need for both chlorine and base is completely avoided.

A great leap forward toward the general synthesis of P-stereogenic compounds: Heating H3 PO2 with (-)-menthol and paraformaldehyde gives easily crystallized menthyl hydroxymethyl-H-phosphinate (1). From this product, virtually any P-stereogenic compound can be synthesized.

Organophosphorus compounds are important in everyday applications ranging from agriculture to medicine and are used in flame retardants and other materials. Although organophosphorus chemistry is known as a mature and specialized area, researchers would like to develop new methods for synthesizing organophosphorus compounds to improve the safety and sustainability of these chemical processes. The vast majority of compounds that contain a phosphorus-carbon bond are manufactured using phosphorus trichloride (PCl3) as an intermediate. However, these reactions require chlorine, and researchers would like to avoid the use of PCl3 and develop safer chemistry that also decreases energy consumption and minimizes waste. Researchers have already proposed and discussed two primary strategies based on elemental phosphorus (P4 or Pred) or on phosphine (PH3) as alternatives to PCl3. However, phosphinates, an important class of phosphorus compounds defined as any compound with a phosphorus atom attached to two oxygens, R(1)R(2)P(O)(OR) (R(1)/R(2) = hydrogen/carbon), offer another option. This Account discusses the previously neglected potential of these phosphinates as replacements of PCl3 for the preparation of organophosphorus compounds. Because of their strong reductive properties, industry currently uses the simplest members of this class of compounds, hypophosphites, for one major application: electroless plating. In comparison with other proposed PCl3 surrogates, hypophosphorous derivatives can offer improved stability, lower toxicity, higher solubility, and increased atom economy. When their reducing power is harnessed to form phosphorus-carbon or phosphorus-oxygen bonds, these compounds are also rich and versatile precursors to organophosphorus compounds. This Account examines the use of transition metal-catalyzed reactions such as cross-coupling and hydrophosphinylation for phosphorus-carbon bond formation. Because the most important industrial organophosphorus compounds include compounds triply or quadruply bound to oxygen, I also discuss controlled transfer hydrogenation for phosphorus-oxygen bond formation. I hope that this Account will further promote research in this novel and exciting yet much underdeveloped area of phosphinate activation.

The room-temperature hydrophosphinylation of unactivated monosubstituted alkenes using phosphinates (ROP(O)H2) and catalytic NiCl2 in the presence of dppe is described. The method is competitive with prior palladium-catalyzed reactions and uses a much cheaper catalyst and simple conditions. The scope of the reaction is quite broad in terms of unactivated terminal olefins, proceeds at room temperature, often avoids chromatographic purification, and allows one-pot conversion to various organophosphorus compounds.

Two generally applicable systems have been developed for the cross-coupling of P(O)H compounds with Csp2X and related partners. Palladium catalysis using a ligand/additive combination, typically either xantphos/ethylene glycol or 1,1′-bis(diphenylphosphino)ferrocene/1,2-dimethoxyethane, with diisopropylethylamine as the base, proved to be generally useful for the synthesis of numerous PC containing compounds. Routinely, 2 mol% of catalyst are employed (less than half the amount typically employed in most other literature reports). In most cases, excellent results are obtained with a variety of electrophiles (RX, where R=alkenyl, allyl, alkynyl, etc.). The full account of our studies is disclosed, including tandem hydrophosphinylation/coupling and coupling/coupling for doubly catalytic phosphorus-carbon bond formation. The methodology compares favorably with any existing literature report. The use of an additive appears to be a generally useful strategy to control the reactivity of phosphinylidene compounds.

The vast majority of organophosphorus compounds is currently synthesized from phosphorus trichloride (PCl3), even though the final consumer products do not contain reactive phosphorus–chlorine bonds. In order to bypass phosphorus trichloride, significant interest has been devoted to functionalizing elemental phosphorus (P4, the precursor to PCl3), red phosphorus (Pred), or phosphine (PH3). Yet, other industrial-scale precursors are hypophosphorous derivatives (H3PO2 and its alkali salts), but their use as phosphorus trichloride replacements has been completely overlooked. Here, the case is made for an alternative approach to the industrial synthesis of organophosphorus compounds based on hypophosphites.

The alkylation of alkyl phosphinates and some H-phosphonate diesters is promoted by the base DBU. Only more reactive alkyl halides react in preparatively useful yields. However, the method provides easy access to important H-phosphinate building blocks, without the need for a protecting group strategy or metal catalysts. The reaction is conveniently conducted at, or below, room temperature. The preparation of methyl-H-phosphinate esters is particularly interesting as it avoids the heretofore more common use of methyldichlorophosphine MePCl2.

(Hydroxymethyl)phosphorus compounds are well-known and valuable compounds in general; however the use of (hydroxymethyl)phosphinates R(1)P(O)(OR(2))CH(2)OH in particular has been much more limited. The potential of this functionality has not yet been fully realized because the mild unmasking of the hydroxymethyl group was not available. The mild oxidative conversion of R(1)P(O)(OR(2))CH(2)OH into R(1)P(O)(OR(2))H using the Corey-Kim oxidation is described. Other reactions preserving the methylene carbon are also reported.

The first metal-catalyzed hydrophosphinylation of unsaturated hydrocarbons with H-phosphinic acids is described. A strategy to activate the PH bond through control of the tautomeric equilibrium using ethylene glycol is described. The reactions also avoid chromatographic purification.

The palladium-catalyzed cross-coupling reaction between H-phosphinate esters and chloroarenes or chloroheteroarenes is described. This reaction is the first general metal-catalyzed phosphorus-carbon bond-forming reaction between a phosphorus nucleophile and chloroarenes.

The regioselectivity of the palladium-catalyzed hydrophosphinylation of terminal alkynes was investigated. Complementary conditions to achieve the predominant formation of either the linear or the branched alkenyl- H -phosphinate products were identified. With Pd/xantphos in acetonitrile, the linear isomer is generally obtained with good to excellent selectivity, and E -stereospecificity. On the other hand, by using Pd/dppf in the non-polar solvent toluene, good selectivity for the branched alkenyl- H -phosphinate is typically observed. The role of various reaction parameters is studied.

Various heterocycles containing phosphorus and nitrogen are easily synthesized from readily available H-phosphinate building blocks. Aminomethylation of these H-phosphinates is followed by in situ cyclization through substitution or cross-coupling to produce novel heterocycles in moderate to good yields.

The design, synthesis, and evaluation of a series of novel inhibitors of aspartate transcarbamoylase (ATCase) are reported. Several submicromolar phosphorus-containing inhibitors are described, but all-carboxylate compounds are inactive. Compounds were synthesized to probe the postulated cyclic transition-state of the enzyme-catalyzed reaction. In addition, the associated role of the protonation state at the phosphorus acid moiety was evaluated using phosphinic and carboxylic acids. Although none of the synthesized inhibitors is more potent than N-phosphonacetyl-L-aspartate (PALA), the compounds provide useful mechanistic information, as well as the basis for the design of future inhibitors and/or prodrugs.

H-Phosphinates obtained through various methodologies are protected directly by the reaction with triethyl orthoacetate. The resulting products can be manipulated easily, andvarious synthetic reactions are presented. For example, application to the synthesis of aspartate transcarbamoylase (ATCase) or kynureninase inhibitors are illustrated. Other reactions, such as Sharpless' asymmetric dihydroxylation, or Grubbs' olefin cross-metathesis are also demonstrated. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Medicinal surface modification of silicon nanowires (SiNWs) with selected bisphosphonates, such as the known anti-osteoporotic drug alendronate, is described. In terms of specific assays relevant to orthopedic applications, the impact of selected bisphosphonates attachment on acellular calcification in simulated plasma is reported. To further investigate biocompatibility, proliferation assays of these modified nanowires were carried out using an orthopedically relevant cell line, mesenchymal stem cells derived from mouse stroma. It is found that the identity of the bisphosphonate ligand strongly and sensitively impacts their resultant cytotoxicity.

The syntheses and X-ray analyses of triphenylmethyl (trityl=Tr) phosphorus compounds are reported and the structural similarities, differences and 31P chemical shifts compared. A series of seven trityl-substituted phosphorus-containing compounds have been characterized by single crystal X-ray diffraction. Ph3CPPh2, 1, a bulky P(III) compound crystallizes in the triclinic space group $$ {\text{P}}\overline{1} $$ , a = 7.5624(6) A, b = 9.5470(8) A, c = 16.9722(14) A, α = 83.4720(10)°, β = 80.541(2)°, γ = 68.1580(10)°, the borane complex of 1, 2, Ph3CPPh2(BH3) crystallizes as monoclinic colorless crystals, P21/c, a = 10.0972(12) A, b = 9.6955(12) A, c = 25.197(3) A, β = 90.258(2)°. The analogous methyl substituted, 3, Ph3CPMe2(BH3) is monoclinic, C2/c, a = 15.628(3) A, b = 12.770(3) A, c = 18.406(4) A, β = 103.968(3)°. Compounds 4–7 are trityl substituted P(V) compounds: Ph3CP(Ph)(O)(OH), 4, crystallizes in the triclinic space group $$ {\text{P}}\overline{1} $$ , a = 8.9847(18) A, b = 9.7443(19) A, c = 12.786(3) A, α = 72.045(3)°, β = 72.031(3)°, γ = 78.769(3)°. Esterification of 4 affords TrCP(O)(Ph)OBn 5, space group, P21/c, a = 7.9196(5) A, b = 31.701(2) A, c = 19.8062(13) A, β = 99.7750(10)°. A phosphonate diester was also characterized, Ph3CP(O)(OEt)2, 6, triclinic, $$ {\text{P}}\overline{1} $$ , a = 7.9521(17) A, b = 9.2205(19) A, c = 14.471(3) A, α = 85.906(4)°, β = 83.031(4)°, γ = 68.283(4)°. Treatment of the trityl H-phosphinic acid, Ph3CPO2H2, with elemental selenium yields yellow crystals of 7, [Ph3CP(O)(OH)Se]2, P21/c, a = 9.0603(4) A, b = 22.3652(11) A, c = 16.9134(7) A, β = 107.035(2)°. In our efforts to isolate a nickel-phosphine complex, two Ni(II) complexes were crystallographically analyzed, [Ni(OP(H)Ph2)6]2BF4 − 8 and 9. Complex 8 with an uncoordinated BF4 − ion crystallizes as yellow orthorhombic crystals, Pbca, a = 18.8247(12) A, b = 18.5518(12) A, c = 21.0976(14) A, while crystals of 9 are trigonal, $$ {\text R} {\bar 3} {\text c} $$ , a = b = 13.1545(12) A, c = 68.461(9) A. The syntheses and X-ray analyses of triphenylmethyl (trityl=Tr) phosphorus compounds are reported and the structural similarities, differences and 31P chemical shifts compared.

The facile synthesis of various P–C–P compounds is described, based on the reaction of phosphorus carbenoids with organoboranes, followed by reaction with phosphorus electrophiles. Using this approach, symmetrically and differentially substituted 1,1-bisphosphorus compounds can be obtained in good yields. A number of novel P–C–P motifs are described for the first time.

Phosphonothioic and boranophosphonic acids have been structurally characterized for the first time by single X-ray crystallography. These two functional groups, and the corresponding phosphonic acid, were all conveniently synthesized in high yields from trityl H-phosphinic acid (Ph3CPO2H2). The resulting trityl-substituted series: Ph3CP(O)(OH)2, Ph3CP(S)(OH)2, Ph3CP(O)(BH3 −)(OH)]LH+ (L = Lewis base) is fully characterized by spectroscopic methods, and the structural characteristics are compared. The results indicate that boranophosphonic acids should be investigated anytime a bioactive phosphonic acid has been identified. The solid state arrangements of the synthesized compounds are also discussed.

The reactions of phosphinylidene-containing compounds with unactivated unsaturated hydrocarbons are reviewed. The review is organized by phosphorus-containing functional group types. Free-radical and metal-catalyzed additions of R1R2P(O)H to alkenes, alkynes, and related compounds deliver functionalized organophosphorus compounds RP(O)R1R2, including H-phosphinates, phosphinates, tertiary phosphane oxides, and phosphonates. The review covers the literature up to February 2008.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

The reaction between aminomethylphosphonic acid (ampa) and the metal salts of Zn, Cd, Hg, Pb, Ag, and Cu afforded seven metal-phosphonate polymers with unique structural features and includes the synthesis of a bimetallic metal-organic framework (Cu/Ag). The characterization of these metal phosphonates is reported by means of infrared spectroscopy, 1 H-NMR, 31 P-NMR, X-ray crystallography, energy dispersive X-ray (EDX), and thermogravimetric analysis (TGA). Individual structural features are compared based on the preferred coordination mode of ampa and the geometrical requirements for each metallic center that manipulates the structural motif.

The reactions of AlCl 3.6H 2O and GaCl 3 with 2-pyridylphosphonic acid (2PypoH 2) and 4-pyridylphosphonic acid (4PypoH 2) afford cyclic aluminum and gallium phosphonate structures of [(2PypoH) 4Al 4(OH 2) 12]Cl 8.6H 2O ( 1), [(4PypoH) 4Al 4(OH 2) 12]Cl 8.11H 2O ( 2), [(2PypoH) 4Al 4(OH 2) 12](NO 3) 8.7H 2O ( 3), [(2PypoH) 2(2Pypo) 4Ga 8Cl 12(OH 2) 4(thf) 2](GaCl 4) 2..8thf ( 4), and [(2PypoH) 2(2Pypo) 4Ga 8Cl 12(OH 2) 4(thf) 2](NO 3) 2.9thf ( 5). Structures 1- 3 feature four aluminum atoms bridged by oxygen atoms from the phosphonate moiety and show structural resemblance to the secondary building units found in zeolites and aluminum phosphates. The gallium complexes, 4 and 5, have eight gallium atoms bridged by phosphonate moieties with two GaCl 4 (-) counterions present in 4 and nitrate ions in 5. The cage structures 1- 3 are interlinked by strong hydrogen bonds, forming polymeric chains that, for aluminum, are thermally robust. Exchange of the phosphonic acid for the more flexible 4PyCH 2PO 3H 2 afforded a coordination polymer with a 1:1 Ga:P ratio, {[(4PyCH 2PO 3H)Ga(OH 2) 3](NO 3) 2.0.5H 2O} x ( 6). Complexes 1- 6 were characterized by single-crystal X-ray diffraction, NMR, and mass spectrometry and studied by TGA.

Hypophosphorous compounds (MOP(O)H(2), M = H, R(3)NH) effectively participate in metal-catalyzed C-P bond-forming reactions with allenes, dienes, and activated allylic electrophiles under mild conditions. The catalytic system Pd(2)dba(3)/xantphos is crucial to avoid or minimize the competitive reductive transfer-hydrogenation pathway available to hypophosphorous acid derivatives. Further investigation into the allylation mechanism provided access to the analogy allylic acetate-allylic phosphinate, which then led to the development of a Pd-catalyzed rearrangement of preformed allylic phosphinates esters and, ultimately, to a catalytic dehydrative allylation of hypophosphorous acid with allylic alcohols. The reactions disclosed herein constitute efficient synthetic approaches, not only to prepare allylic H-phosphinic acids but also their esters via one-pot tandem processes. In addition, the potential of H-phosphinates as useful synthons for the preparation of other organophosphorus compounds is demonstrated.

Organoboranes react with phosphorus-containing carbenoids to produce a variety of functionalized organophosphorus compounds under mild conditions. In some cases, selective migration of one group attached to boron can be observed. Phosphonite-borane complexes are introduced as novel synthons for the synthesis of phosphinic esters.

Five new metal pyridylphosphonate polymers have been prepared, fully characterized, and their room-temperature luminescence probed. The reaction of (2-pyridyl)phosphonic acid (2pypo) with ZnX2 (X = Br, Cl) afforded two-dimensional polymers [Zn(X)(2pypo)]n {X = Cl = (1), X = Br = (2)}, which feature cyclic 12-membered Zn–O–P cores that are interlinked by bridged oxygen atoms from the phosphonate moiety. From the room–temperature, aqueous reactions of 2pypo and the corresponding metal salts, the one-dimensional polymers [Cd(μ-Cl)2(2pypo)]n (3) and [Hg(2pypo)]n (4) were isolated in moderate yield. The one-dimensional structure of 3 is supported through bridging chlorides and two η2-phosphonate oxygen atoms, while 4 is a highly symmetrical polymer that exhibits pyridyl nitrogen coordination to the mercury center and uses two μ2-oxygen atoms to polymerize. Reaction of silver triflate (CF3SO3Ag) with 2pypo afforded a crystalline silver polymer that displays a zig-zag arrangement of silver atoms with argentophilic interactions and that is stablized through bridged triflate and phosphonate moieties. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

A novel approach to H-phosphonates from hypophosphorous acid using a transfer hydrogenation process was developed. This method is atom-economical, environmentally friendly, catalytic, and efficient, leading easily to H-phosphonate monoesters or ammonium salt in moderate to good yields.

An efficient and general procedure was developed for the direct alkylation of H-phosphinate esters with LHMDS at low temperature. The simplicity of the reaction allows the use of various H-phosphinate esters and takes place with a wide range of electrophiles. The approach can be employed to access some GABA analogues or precursors to GABA analogues. The isolated yields are moderate to good. This is the first report of an alkylation with a secondary iodide or a primary chloride.

The Mn(II)/Mn(IV) system was used to achieve the bisfunctionalization of alkenes with phosphorus and chlorine in moderate to good yields. A variety of phosphinylidene-containing (P(O)H) compounds were examined. When the phosphorus reagent is limiting, the reaction yield is generally in the 40–50% range, although the structure of the organophosphorus starting material greatly influences it. The reaction is simple and inexpensive and the β-chloro-phosphinoyl products are versatile intermediates. For example, elimination with DBU gave the corresponding α,β-unsaturated phosphorus compound stereoselectively.

Phosphinylidene compounds R1R2P(O)H are important functionalities in organophosphorus chemistry and display prototropic tautomerism. Quantifying the tautomerization rate is paramount to understanding these compounds’ tautomerization behavior, which may impact their reactivities in various reactions. We report a combined theoretical and experimental study of the initial tautomerization rate of a range of phosphinylidene compounds. Initial tautomerization rates are found to decrease in the order H3PO2 > Ph2P(O)H > (PhO)2P(O)H > PhP(O) (OAlk)H > AlkP(O)(OAlk)H ≈ (AlkO)2P(O)H, where “Alk” denotes an alkyl substituent. The combination of computational investigations with experimental validation establishes a quantitative measure for the reactivity of various phosphorus compounds, as well as an accurate predictive tool.