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Synthesis of phosphine oxides

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Sodium exhibits better efficacy and selectivity than Li and K for converting Ph3P(O) to Ph2P(OM). A subsequent reaction with alkyl halides or with aryl halides in the presence of a Pd catalyst provides phosphine oxides in good to excellent yields.
J.-Q. Zhang, E. Ikawa, H. Fujino, Y. Naganawa, Y. Nakajima, L.-B. Han, J. Org. Chem., 2020, 85, 14166-14173.

An efficient Ni-catalyzed coupling of a wide range of arylboronic acids with H-phosphites, H-phosphinate esters, and H-phosphine oxides provides various aryl-phosphorus compounds, including valuable triarylphosphine oxides, in very good yield.
G. Hu, W. Chen, T. Fu, Z. Peng, H. Qiao, Y. Gao, Y. Zhao, Org. Lett., 2013, 15, 5363-5365.

A copper-catalyzed reaction of phosphorus nucleophiles with diaryliodonium salts at room temperature delivers products of a P-C bond formation in high yields within a short reaction time of 10 min. The method can be easily adapted to large-scale preparations. With unsymmetrical iodonium salts, nucleophilic substitution occurs preferentially on the sterically hindered aromatic ring or the more electron-deficient ring.
J. Xu, P. Zhang, Y. Gao, Y. Chen, G. Tang, Y. Zhao, J. Org. Chem., 2013, 78, 8176-8183.

A palladium-catalyzed C-P bond formation between dichloroheterocycles and secondary phosphine oxides provides heterocyclic compounds bearing two tertiary phosphine oxides in good yields. Extension of the methodology to monohalohetarenes and monohaloarenes was successfully carried out; the steric and electronic properties of the halides were varied widely.
G. G. Zajkirova, D: Y. Mladentsev, N. E. Borisova, Synthesis, 2019, 51, 2379-2386.

A broad range of aryl iodides are efficiently coupled with secondary phosphine oxides using low loadings of a catalyst formed in situ from tris(dibenzylideneacetone)dipalladium and Xantphos.
A. J. Bloomfield, S. B. Herzon, Org. Lett., 2012, 14, 4370-4373.

A convenient and efficient copper-catalyzed approach for P-arylation of organophosphorus compounds containing P-H uses the commercially available and inexpensive proline and pipecolinic acid as ligands. The method can provide an entry to arylphosphonates, arylphosphinates and arylphosphine oxides.
C. Huang, X. Tang, H. Fu, Y. Jiang, Y. Zhao, J. Org. Chem., 2006, 71, 5020-5022.

The combination of thioxanthen-9-one and a nickel catalyst mediates an efficient photocatalytic P(O)-C(sp2) coupling of (hetero)aryl halides with H-phosphine oxides or H-phosphites under the irradiation of visible light to provide arylphosphine oxides and arylphosphonates in good yields. This transformation tolerates a wide range of functional groups and proceeds efficiently on a gram scale.
D.-L. Zhu, S. Jiang, Q. Wu, H. Wang, L.-L. Chai, H.-Y. Li, H.-X. Li, Org. Lett., 2021, 23, 160-165.

A Pd/Xiao-Phos-catalyzed cross-coupling reaction of easily accessible secondary phosphine oxides and aryl bromides provides rapid access to P-chiral phosphine oxides. The reaction proceeds efficiently with a wide array of reaction partners to deliver various tertiary phosphine oxides.
Q. Dai, W. Li, Z. Li, J. Zhang, J. Am. Chem. Soc., 2019, 141, 20556-20564.

An iodide-accelerated, palladium-catalyzed C-P bond-forming reaction of aryl nonaflates provides a broad range of aryl phosphine oxides, aryl phosphonates and an aryl phosphinate. The straightforward synthesis of stable, isolable aryl nonaflates, allows facile preparation of aryl phosphorus target compounds from readily available phenol starting materials.
H. McErlain, L. M. Riley, A. Sutherland, J. Org. Chem., 2021, 86, 17036-17049.

Diacyl peroxides, generated in situ from aliphatic acids and H2O2, serve as a source for alkyl radicals and also an initiator for the generation of phosphorus radicals from H-P(O) compounds. A subsequent CuI-catalyzed cross-coupling of alkyl- and phosphorus-centered radicals provides alkylated phosphorous compounds in good yields.
C.-K. Li, Z.-K. Tao, A. Shoberu, W. Zhang, J.-P. Zou, Org. Lett., 2022, 24, 6083-6087.

A Cu-catalyzed enantioselective arylation of secondary phosphine oxides with diaryliodonium salts enables the synthesis of tertiary phosphine oxides with high enantiomeric excess. The process converts a wide range of substrates and leads to products that are well-established P-chiral catalysts and ligands.
R. Beaud, R. J. Phipps, M. J. Gaunt, J. Am. Chem. Soc., 2016, 138, 13183-13186.

NiCl2 • 6 H2O/Zn catalyzes the cross-coupling of aryl halides with diphenylphosphine oxide (Ph2P(O)H) and (RP)-(−)-menthyl benzylphosphinate in water under relatively mild conditions.
X. Zhang, H. Liu, X. Hu, G. Tang, J. Zhu, Y. Zhao, Org. Lett., 2011, 13, 3478-3481.

A novel and highly efficient Pd-catalyzed cross-coupling of triarylbismuths with various P(O)-H compounds proceeds smoothly without exclusion of moisture or air and provides valuable arylphosphonates, arylphosphinates, and arylphosphine oxides, with high atom-economy, operational simplicity of the procedure, and good to high yield.
T. Wang, S. Sang, L. Liu, H. Qiao, Y. Gao, Y. Zhao, J. Org. Chem., 2014, 79, 608-617.

In a Rh-catalyzed highly regio- and enantioselective synthesis of allylic phosphine oxides in the presence of a chiral bisoxazoline-phosphine ligand, the use of α-hydroxylalkylphosphine oxides as substrates to keep a low concentration of the secondary phosphine oxides is essential for the high yields.
B. Li, M. Liu, S. U. Rehman, C. Li, J. Am. Chem. Soc., 2022, 144, 2893-2898.

A combination of t-BuOK and 18-crown-6 enabled a coupling of a wide range of substituted benzyl ammonium salts with heteroatom nucleophiles, i.e. hydrogen phosphoryl compounds, alcohols, thiols, and amines. Good functional group tolerance was demonstrated.
L. Liu, Y. Tang, K. Wang, Z. Huang, T. Chen, J. Org. Chem., 2021, 86, 4159-4170.

A visible-light-driven redox-neutral phosphonoalkylation of alkene-bearing alkyl sulfonates provides a variety of organophosphorus-containing three-membered carbocyclic scaffolds. The transition-metal-free protocol displays good functional group tolerance, broad substrate scope, high yields, and mild reaction conditions.
Y.-M. Jiang, J. Liu, Q. Fu, Y.-M. Yu, D.-G. Yu, Synlett, 2021, 32, 378-382.

An efficient use of arynes for C-P bond construction enables a mild process for the synthesis of aryl-phosphonates, -phosphinates, and -phosphine oxides. The reaction circumvents the relatively harsh reaction conditions using transition-metal-catalyzed P-arylation (Arbuzov/Hirao reaction).
R. A. Dhokale, S. B. Mhaske, Org. Lett., 2013, 15, 2218-2221.

Pd-catalyzed phosphorylations of thioesters provide aryl or alkenyl phosphoryl compounds through decarbonylative coupling, whereas benzyl phosphoryl compounds were produced through deoxygenative coupling when the reactions were carried out in the presence of only a base.
K. Xu, L. Liu, Z. Li, T. Huang, K. Xiang, T. Chen, J. Org. Chem., 2020, 85, 14653-14663.

Pd-catalyzed phosphorylations of thioesters provide aryl or alkenyl phosphoryl compounds through decarbonylative coupling, whereas benzyl phosphoryl compounds were produced through deoxygenative coupling when the reactions were carried out in the presence of only a base.
K. Xu, L. Liu, Z. Li, T. Huang, K. Xiang, T. Chen, J. Org. Chem., 2020, 85, 14653-14663.

A nickel-catalyzed benzylic substitution of secondary phosphine oxide provides dialkylated P-stereogenic tertiary phosphine oxides with high enantioselectivities. The reaction was performed under mild conditions with commercially available benzyl chlorides and bench stable secondary phosphine oxides, exhibiting broad functional group tolerance.
W.-Q. Cai, Q. Wei, Q.-W. Zhang, Org. Lett., 2022, 24, 1258-1262.

A convenient rhodium-catalyzed regio- and stereoselective hydrophosphinylation of alkynes provides (E)-alkenylphosphine oxides in very good yields.
L.-B. Han, C.-Q. Zhao, M. Tanaka, J. Org. Chem., 2001, 66, 5929-5932.

In a decarboxylative cross-coupling of alkynyl acids in the presence of 10 mol % of CuCl without added ligand, base, and additive, various alkynyl acids reacted with H-phosphine oxides to afford E-alkenylphosphine oxides with operational simplicity, broad substrate scope, and absolute stereoselectivity.
G. Hu, Y. Gao, Y. Zhao, Org. Lett., 2014, 16, 4464-4467.

A radical-promoted decarboxylation enables a transition-metal-free phosphorylation of cinnamic acids with P(O)H compounds under mild conditions. This method provides simple, efficient, and versatile access to a broad range of valuable (E)-alkenylphosphine oxides in good yields.
L. Liu, D. Zhou, J. Dong, Y. Zhou, S.-F. Yin, L.-B. Han, J. Org. Chem., 2018, 83, 4190-4196.

A practical and efficient photoinduced decarboxylative/dehydrogenative coupling of α-fluoroacrylic acids with phosphine oxides provides monofluoroalkenyl phosphine oxides. Various α-fluoroacrylic acids and P(O)H compounds were converted into corresponding products with excellent E-stereoselectivity in good yields. Monofluoroalkenyl silanes can be obtained under similar conditions.
X.-Y. Lu, H.-Y. Pan, R. Huang, K. Yang, X. Zhang, Z.-Z. Wang, Q.-Q. Tao, G.-X. Yang, H.-P. Zhou, Org. Lett., 2023, 25, 2476-2481.

A palladium-catalyzed hydrophosphorylation of alkynes with P(O)-H compounds (i.e., H-phosphonates, H-phosphinates, secondary phosphine oxides, and hypophosphinic acid) provides Markovnikov adducts in high yields with high regioselectivity for both aromatic and aliphatic alkynes. The reaction tolerates a wide variety of functional groups.
T. Chen, C.-Q. Zhao, L.-B. Han, J. Am. Chem. Soc., 2018, 140, 3139-3155.

A silver-free palladium-catalyzed dehydrogenative phosphorylation of terminal alkynes with hydrogen phosphine oxides produces the corresponding value-added alkynylphosphine oxides in very good yields. This reaction could be easily conducted at gram scales without any decrease of efficiency.
J.-Q. Zhang, T. Chen, J.-S. Zhang, L.-B. Han, Org. Lett., 2017, 19, 4692-4695.

Efficient Cs2CO3-promoted phosphorylations or phosphinylations of various 1,1-dibromo-1-alkenes with readily available trialkyl phosphites, ethyl diphenylphosphinite, or diethyl phenylphosphonite under metal-free conditions provide valuable alkynylphosphonates, -phosphinates, and -phosphine oxides in very good yields.
Y. Wang, J. Gan, L. Liu, H. Yuan, Y. Gao, Y. Liu, Y. Zhao, J. Org. Chem., 2014, 79, 3678-3683.

A direct and convenient coupling of propargylic substrates with diphenylphosphine oxide in the presence of Tf2O and 2,6-lutidine provides attractive allenylphosphoryl skeletons with high atom and step economy under metal free conditions.
C.-H. Yang, H. Fan, H. Li, S. Hou, X. Sun, D. Luo, Y. Zhang, Z. Yang, J. Chang, Org. Lett., 2019, 21, 9438-9441.

A facile and efficient copper-catalyzed direct C-P cross-coupling of unprotected propargylic alcohols with P(O)H compounds provides valuable allenylphosphoryl frameworks with operational simplicity and high step- and atom-economy under ligand-, base-, and additive-free conditions.
G. Hu, C. Shan, W. Chen, P. Xu, Y. Gao, Y. Zhao, Org. Lett., 2016, 18, 6066-6069.

A catalyst- and solvent-free reaction between secondary phosphine oxides and aliphatic, aromatic and heteroaromatic ketones provides tertiary α-hydroxyphosphine oxides in excellent yield.
N. K. Gusarova, N. I. Ivanova, K. O. Khrapova, P. A. Volkov, A. A. Telezhkin, L. I. Larina, A. V. Afonin, D. V. Pavlov, B. A. Trofimov, Synthesis, 2020, 52, 2224-2232.

An efficient catalyst- and solvent-free addition of secondary phosphine chalcogenides to diverse aldehydes enables an almost quantitative synthesis of tertiary α-hydroxyphosphine chalcogenides under mild conditions (20-52 C, from 10 min to 5 h).
N. K. Gusarova, N. I. Ivanova, P. A. Volkov, K. O. Khrapova, L. I. Larina, V. I. Smirnov, T. N. Borodina, B. A. Trofimov, Synthesis, 2015, 47, 1611-1622.

Visible light mediates a P-H insertion reaction between acylsilanes and H-phosphorus oxides that, upon a subsequent acidic desilylation, delivers a wide variety of α-hydroxyphosphorus oxides in good yields. This method offers operational simplicity, mild conditions, and broad substrate scope.
X. Mo, Y. Xie, L. Wei, X. Gu, M. Zhang, X. Zhang, J. Jiang, Org. Lett., 2023, 25, 2338-2343.

Chlorosilanes mediate a direct coupling of hydrogen phosphine oxides and acyl chlorides for the synthesis of acylphosphine oxides. This new protocol is greener and safer, because it avoids the generation of volatile haloalkanes and the use of oxidants. Moreover, moisture-unstable acylphosphine oxides can also be generated.
J.-Q. Zhang, L.-B. Han, Org. Lett., 2020, 22, 4633-4637.

A general synthetic procedure using 2 eq. of BSA as silylating agent provides H-α-hydroxyphosphinates in very good yields in short times via Abramov reaction. The H-α-hydroxyphosphinates can easily be purified and obtained.
J. Dussart, J. Deschamp, M. Monteil, O. Gager, E. Migianu-Griffoni, M. Lecouvey, Synthesis, 2019, 51, 421-432.

A visible light-mediated photocatalytic decarboxylative oxyphosphorylation of cinnamic acids with diarylphosphine oxides provides the corresponding β-ketophosphine oxides under mild conditions.
H.-F. Qian, C.-K. Li, Z.-H. Zhou, Z.-K. Tao, A. Shoberu, J.-P. Zou, Org. Lett., 2018, 20, 5947-5951.

Potassium carbonate promotes a convenient hydrophosphonylation of alkenes with phosphites in good yields. The reaction offers easy handling, environmental friendliness, and the use of a mild base. A variety of alkenes are tolerated in this reaction.
Z. Huang, W. Liu, S. Li, Y. Yang, S. Guo, H. Cai, Synlett, 2020, 31, 1295-1297.

An asymmetric addition of diarylphosphines to β-substituted enones under mild conditions using a chiral pincer-palladium allows the synthesis of chiral phosphines with excellent enantioselectivity.
J.-J. Feng, X.-F. Chen, M. Shi, W.-L. Duan, J. Am. Chem. Soc., 2010, 132, 5562-5563.

A copper-catalyzed aerobic oxidative/decarboxylative phosphorylation of aryl acrylic acids with P(III)-nucleophiles via the Michaelis-Arbuzov rearrangement provides β-ketophosphine oxides, β-ketophosphinates, and β-ketophosphonates in very good yields. The present reaction could be conducted effectively without the use of a ligand and a base.
B. Xiong, L. Si, L. Zhu, Y. Liu, W. Xu, K.-W. Tang, S.-F. Yin, P.-C. Qian, W.-Y. Wong, J. Org. Chem., 2023, 88, 12502-12518.

Chiral PCN pincer Pd(II) complexes were examined as enantioselective catalysts for the hydrophosphination of enones. Hydrophosphination of 2-alkenoylarenes with diphenylphosphine followed by oxidation with hydrogen peroxide afforded the corresponding chiral phosphine oxides in good yields with very good enantioselectivities.
X.-Q. Hao, J.-J. Huang, T. Wang, J. Lv, J.-F. Gong, M.-P. Song, J. Org. Chem., 2014, 79, 9512-9530.

An efficient acid-catalyzed direct coupling of a wide range of unprotected 2,3-allenols with arylphosphine oxides provides structurally diverse γ-ketophosphine oxides with remarkable functional group tolerance and complete atom-economy under metal- and additive-free conditions. Mechanistic studies showed that this transformation involved a rearrangement and a phospha-Michael reaction.
R. Zhao, X. Huang, M. Wang, S. Hu, Y. Gao, P. Xu, Y. Zhao, J. Org. Chem., 2020, 85, 8185-8195.

Several E and Z configured α,β-unsaturated carbonyl and carboxyl acceptors (including imides) as well as nitroalkenes participate in a palladium(II)-catalyzed conjugate transfer of diphenyl-, dicyclohexyl-, and di-tert-butylphosphinyl groups from silylphosphines in high chemical yields.
V. T. Trepohl, S. Mori, K. Itami, M. Oestreich, Org. Lett., 2009, 11, 1091-1094.

A bis(imidazoline)-phosphoric acid catalyzes an enantioselective hydrophosphonylation of ketimines with phosphine oxides to provide chiral α-quaternary aminophosphorous compounds having a primary amino group in excellent yields and enantioselectivities. Based on experimental results and DFT calculation, transition states were proposed to explain the stereoselectivity of the reaction.
K. Ogura, I. Isozumi, T. Takehara, T. Suzuki, S. Nakamura, Org. Lett., 2022, 24, 8088-8092.


A Pd(OAc)2/Xantphos-based catalyst enabled a deprotonative cross-coupling process between benzyl diphenyl or dicyclohexyl phosphine oxide derivatives and aryl bromides to prepare diarylmethyl phosphine oxides in very good yields.
S. Montel, T. Jia, P. J. Walsh, Org. Lett., 2014, 16, 130-133.