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Article

Pd-Catalyzed Direct Diarylation of Sodium Hypophosphite Enables the Synthesis of Diarylphosphonates

by
Jin Yang
1,
Dangwei Qian
1,
Gangwei Wang
1 and
Shangdong Yang
1,2,*
1
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China
2
State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China
*
Author to whom correspondence should be addressed.
Molecules 2025, 30(7), 1564; https://doi.org/10.3390/molecules30071564
Submission received: 27 February 2025 / Revised: 24 March 2025 / Accepted: 28 March 2025 / Published: 31 March 2025
(This article belongs to the Special Issue Recent Progress in Organophosphorus Chemistry)
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Abstract

:
A facile and efficient method for synthesizing diarylphosphinates from alcohols and aryl halides, using stable, green, and readily available sodium hypophosphite as a phosphorus source, is disclosed herein for the first time. This method offers high-efficiency and excellent functional group tolerance, providing a straightforward approach to synthesizing a broad range of diarylphosphinates from green starting materials with moderate to excellent yields.

1. Introduction

Diarylphosphinates are a class of functional molecules with significant applications in pharmaceuticals [1,2], agrochemicals [3,4], flame retardants [5], ligand scaffolds [6,7], and organic synthesis [8,9]. Representative molecules are illustrated in Scheme 1a. Traditional synthetic methods primarily rely on the moisture-sensitive and toxic phosphorus oxychloride (POCl3) as a phosphorus source (Scheme 1b). These methods generally follow two transformation pathways: First, phosphorus oxychloride reacts with alcohol to yield dichlorophosphates, which subsequently undergo reactions with aryl magnesium bromide reagents to form diarylphosphinates [10,11]. Second, phosphorus oxychloride first reacts with aryl lithium to generate diarylphosphonyl chloride, which then undergoes nucleophilic substitution with alcohol under basic conditions to produce diarylphosphinates [12,13,14]. Furthermore, phosphorus trichloride (PCl3) has also been explored as the starting material, with the synthesis of diaryl phosphine oxide as a key intermediate. This intermediate can then react with alcohol through various strategies, such as the Atherton–Todd process [15,16,17,18], transition-metal-catalyzed coupling [19,20,21,22,23,24], Selectfluor mediated reactions [25], and electro-catalysis [26,27,28,29], to afford diarylphosphinates (Scheme 1c). Although the reactions described above provide useful methods for the synthesis of diarylphosphinates, they have several drawbacks. These include the use of moisture-sensitive and toxic P(O)Cl3 and PCl3 as starting materials, the use of highly reactive aryllithium and aryl magnesium bromide reagents, which lead to poor selectivity and complex operations, poor step economy, and the generation of numerous halide salts, which limit the green and environmentally friendly nature of the process. Therefore, the development of a simple and efficient protocol for the preparation of diarylphosphinates remains highly desirable.
Sodium hypophosphite (NaH2PO2) is a green, safe, stable, and cost-effective phosphorus source, making it a promising substitute for traditional phosphorus trichloride. Using NaH2PO2 in the construction of organophosphorus compounds is more economical in terms of steps and significantly reduces the overall cost—both financially and environmentally [30]. Building on previous research [31,32,33,34,35], we directly utilized sodium hypophosphite as a phosphorus source and achieved the synthesis of diarylphosphinates through a palladium-catalyzed coupling reaction in a “one-pot” manner (Scheme 1d). Compared to previous methods, our approach is more step-efficient, simpler, and more economical, enabling the construction of three new bonds in a single pot.

2. Results and Discussion

2.1. Reaction Condition Optimization

In the initial study, we selected NaH2PO2, isopropyl alcohol, and bromobenzene as standard substrates to identify optimal conditions for the diarylphosphonates’ synthesis (Table 1; see Supplementary Materials for more details). Building on previous work, we first screened activators for sodium hypophosphite in the reaction. However, the target product was not observed when no activator was used, or when benzoyl chloride or sulfonyl chloride served as an activator. Notably, when trimethylacetyl chloride (PivCl) was used as an activator, the target product 3a was obtained with an 83% yield (Table 1, entry 1–4). After identifying the optimal activator, we focused on investigating the influence of bases on the reaction. Through systematic screening, we found that inorganic bases yielded unsatisfactory results, whereas other organic bases such as DBU, Et3N, and DIPEA were all capable of catalyzing the reaction. However, DABCO remained the optimal choice (Table 1, entry 5–9). Subsequently, we investigated the effect of reaction concentration on the process. The reaction proceeded smoothly across a range of concentrations; however, optimal reaction efficiency and economic viability were achieved at a concentration of 0.1 mol/L (Table 1, entry 10–11). During catalyst optimization, we found that Pd(dppe)Cl2 and Pd(PPh3)2Cl2 also promoted the reaction, but with less efficiency than Pd(dppf)Cl2. Inexpensive metal salts such as nickel and cobalt did not exhibit catalytic activity (Table 1, entry 12–15). Solvent screening revealed that PhMe was the optimal solvent, yielding 83% of the target product 3a. When THF and EtOAc were used as solvents, the yields of 3a were 51% and 63%, respectively (Table 1, entry 16–18).

2.2. Expansion of Aryl Halide Substrates and Alcohol Substrates

After establishing the protocol for the direct conversion of NaH2PO2 to arylphosphonate compounds, we next explored the scope of aryl halide coupling partners (Scheme 2). Bromobenzene was initially used as the coupling reagent, yielding isopropyl diphenylphosphonate 3a in 83%. We then investigated the electronic and steric effects of substituents on the benzene ring. The results revealed that steric hindrance significantly affects the reaction. When o-methylbromobenzene, m-methylbromobenzene, and p-methylbromobenzene were used as substrates, only a small amount of the target product was obtained with o-methylbromobenzene. However, increasing the reaction temperature to 120 °C increased the yield of 3b to 42%. The corresponding products (3c, 3d) were obtained in 80% and 87% yields for m-methylbromobenzene and p-methylbromobenzene, respectively. When stronger electron-donating substituents, such as methoxy, were used, product 3e was obtained with an 80% yield. Based on the aforementioned results, we observed that electron-donating substituents exhibited minimal influence on the reaction yields. Next, the effect of electron-withdrawing substituents in the para position of the benzene ring was investigated. The reaction showed good functional group compatibility, with trifluoromethyl, phenyl, ester, acetyl, and cyano groups all compatible. Diarylphosphonates (3f–3j) were obtained in good yields, indicating that electronic effects had minimal impact on the reaction outcome. Notably, when the aromatic ring carried aldehyde and vinyl groups in the para position, products 3k and 3l were obtained in 63% and 58% yields, respectively. Aromatic halides other than the benzene ring also proved suitable for the reaction, as demonstrated by the successful synthesis of biarylphosphates (3m, 3n) from 1-naphthyl triflate and 5-bromoacenaphthene, yielding 80% and 71%, respectively. It is noteworthy that halogenated heteroaromatics can also participate in this reaction. For example, 2-iodothiophene, 5-bromobenzothiophene, 5-bromobenzofuran, and 4-bromo-1,2-methylenedioxybenzene yield the corresponding phosphonate products (3o–3r) in medium to excellent yields under the standard reaction conditions. However, 5-bromoindole does not undergo the reaction under these conditions. Interestingly, 5-bromoquinoline also reacts to yield product 3s under standard conditions. Additionally, unprotected nitrogen heterocyclic substrates lead to products 3t and 3u with moderate to high yields. When naphthone and indenone are used as substrates, products 3v and 3w are obtained with yields of 81% and 89%, respectively. However, alkyl halides are not suitable for this reaction.
After assessing the applicability of aryl halide substrates, we next investigated the scope of alcohol substrates (Scheme 3). The results showed that primary alcohols are highly compatible with this reaction. Short-chain ethanol, long-chain n-octanol, sterically hindered neopentyl alcohol, and cyclopropanol all participated effectively, yielding the corresponding diarylphosphinates (4a–4d) with excellent yields. The reaction also proceeds smoothly when secondary alcohols are used as substrates. Cyclobutanol, with high ring tension, and cyclohexanol, with low ring tension, both participate in the reaction, yielding products 4e and 4f in 59% and 84% yields, respectively. Increasing the steric hindrance of the secondary alcohol, 3-pentanol, leads to the target product 4g with a medium to high yield. Tertiary alcohols with high steric hindrance are not suitable for this reaction, as no reaction occurs when tert-butanol is used as a substrate. We then investigated alcohols containing various functional groups, including methoxy, chlorine, terminal olefins, trifluoromethyl, and ester groups. We found that the functional groups in the alcohol molecules exhibit good compatibility in this reaction and are well-preserved, enabling further conversion of the products (4i–4m). Alcohols containing sulfur atoms, such as 2-methylthioethanol, were also identified as suitable substrates for this reaction (4n). When tetrahydrofurfuryl alcohol and chiral (R)-(-)-glyceroacetone aldehyde participate in the reaction, the corresponding target products (4o, 4p) are obtained with moderate yields. It is gratifying that this reaction can introduce phosphorus atom into drug molecules, such as alcohols derived from xanthene-9-carboxylic acid, ibuprofen, and naproxen, yielding target products 4q, 4r, and 4s with yields of 68%, 69%, and 77%, respectively. This product may have potential medicinal value. Surprisingly, alcohol substrates with complex structures also react smoothly, yielding product 4t. Finally, we investigated the effect of nitrogen atoms on the reaction and found that the target product 4u, with a yield of 64%, can still be obtained under standard conditions when chromol containing active nitrogen–hydrogen participates in the reaction. When N-(3-hydroxypropyl) phthalimide is used, the desired product 4v is obtained with an 83% yield.

2.3. Gram-Scale Reaction of 3a and Related Transformations

To demonstrate the practical applicability of this strategy in synthetic chemistry, a reaction on a 14.0 mmol scale was performed under standard conditions, yielding 3a in 76% (Scheme 4).

2.4. Syntheses of Proposed Reaction Intermediates

Based on the reported literature and our understanding of the system [36,37,38], we believe that hypophosphite esters and aryl H-phosphonates are key intermediates in this reaction. To verify the validity of this hypothesis, several control experiments were conducted (Scheme 5). Initially, a toluene solution of isopropyl phosphinate was prepared by refluxing the aniline salt of hypophosphorous acid with isopropyl silicate in toluene under an argon atmosphere [39], which was subsequently used as a stock solution for further reactions. The nuclear magnetic resonance (NMR) conversion of isopropyl phosphinate 9 was determined to be 100% using triphenylphosphine as the internal standard (Scheme 5a). During the optimization of reaction conditions, it was also found that using diisopropylethylamine as a base, instead of triethylenediamine, yields isopropyl phenylphosphinate 10 (Scheme 5b). Subsequently, isopropyl phosphinate 9 and isopropyl phenylphosphinate 10 were used as substrates in coupling reactions with bromobenzene, yielding isopropyl diphenylphosphinate product 3a in both cases (Scheme 5c,d). This result supports the hypothesis that hypophosphite esters and arylphosphonic acid esters are key intermediates in the reaction.

2.5. Possible Mechanisms

Based on our understanding of the coupling reaction catalyzed by transition metals, along with the results from controlled experiments, we propose a possible reaction mechanism (Scheme 6). First, sodium hypophosphite reduces the divalent palladium catalyst in situ to a zero-valent palladium catalyst, which undergoes oxidative addition with the aryl bromide substrate, forming the divalent palladium intermediate (Int-A). Next, isopropyl phosphinate 9, generated in situ from sodium hypophosphite, trimethylacetyl chloride, and isopropanol, acts as a nucleophilic reagent and reacts with the divalent palladium intermediate (Int-A) in the presence of a base to form a new divalent palladium intermediate (Int-B). The divalent palladium intermediate (Int-B) then undergoes a reductive elimination reaction to generate aryl phosphonate 10 and release the zero-valent palladium catalyst. Next, aryl phosphonate 10 reacts with the divalent palladium intermediate (Int-A) in the presence of a base, forming another divalent palladium intermediate (Int-C). Finally, the divalent palladium intermediate (Int-C) undergoes reductive elimination to generate the isopropyl diphenylphosphinate 3a, releasing the zero-valent palladium catalyst to continue the catalytic cycle.

3. Conclusions

In summary, we have developed a palladium-catalyzed multi-component reaction for the simultaneous construction of two carbon–phosphine bonds and one oxygen–phosphine bond, using stable, green, inexpensive, and abundant sodium hypophosphite as a phosphorus source. This method enables the synthesis of a series of diaryl phosphonates. The simple and efficient synthesis of diaryl phosphonates with high functional group tolerance demonstrates the potential of this approach for applications in biologically active molecules, catalytic ligands, and organophosphorus compounds.

4. Materials and Methods

General: 1H NMR, 13C NMR, 31P NMR, and 19F NMR spectra were recorded at room temperature using an Avance-400 instruments (Bruker, Billerica, MA, USA) (1H NMR at 400 MHz, 13C NMR at 101 MHz, 31P NMR at 162 MHz, and 19F NMR at 376 MHz). NMR spectra of all products were reported in ppm with reference to solvent signals [1H NMR: CD(H)Cl3 (7.26 ppm), 13C NMR: CD(H)Cl3 (77.00 ppm)]. Signal patterns are indicated as s, singlet; d, doublet; dd, doublets of doublet; t, triplet; and m, multiplet. The mass spectrometry was performed in the positive electrospray ionization (ESI+) mode. Reactions were monitored by thin-layer chromatography. Column chromatography (petroleum ether/ethyl acetate) was performed on silica gel (200–300 mesh). Analytical grade solvents and commercially available reagents were purchased from commercial sources and used directly without further purification unless otherwise stated.
Typical Procedure for Synthesis of Diarylphosphonates: To a 10 mL reaction tube, aryl halide (0.2 mmol, 1.0 eq.), sodium hypophosphite (0.4 mmol, 2.0 eq.), and Pd(dppf)Cl2 (0.005 mmol, 2.5 mol%) were added. The reaction tube was sealed with a rubber stopper, and the air was replaced with argon three times. Anhydrous THF (2 mL), alcohol (1.6 mmol, 8.0 eq.), and PivCl (0.8 mmol, 4.0 eq.) were then added by syringe. The mixture was stirred in a 100 °C oil bath for 28 h until the complete consumption of the starting material was confirmed by TLC analysis. After the reaction, the solution was filtered and washed with ethyl acetate. The combined filtrates were concentrated under reduced pressure, and the crude product was purified by silica-gel column chromatography (eluent: petroleum ether/ethyl acetate = 2/1–1/1), yielding the desired product.
Isopropyl diphenylphosphinate (3a) [40]. Colorless oil. Isolated yield: 83% (21.6 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.87–7.77 (m, 4H), 7.52–7.47 (m, 2H), 7.45–7.41 (m, 4H), 4.85–4.40 (m, 1H), 1.35 (d, J = 6.2 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 133.13 (s), 131.93 (d, J = 2.8 Hz), 131.77 (s), 131.62 (d, J = 10.0 Hz), 128.41 (d, J = 13.0 Hz), 70.20 (d, J = 6.0 Hz), 24.32 (d, J = 4.2 Hz). 31P NMR (162 MHz, CDCl3) δ 29.73 (s). HRMS (ESI): [M + H]+ calcd for C15H18O2P+ 261.1039; found 261.1037.
Isopropyl di-o-tolylphosphinate (3b). Colorless oil. Isolated yield: 42% (12.1 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 8.09–7.85 (m, 2H), 7.39 (t, J = 7.5 Hz, 2H), 7.33–7.23 (m, 2H), 7.20–7.12 (m, 2H), 4.82–4.56 (m, 1H), 2.33 (s, 6H), 1.33 (d, J = 6.2 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 141.42 (d, J = 11.3 Hz), 133.46 (d, J = 9.7 Hz), 132.04 (d, J = 2.7 Hz), 131.30 (d, J = 12.6 Hz), 130.16 (s), 125.41 (d, J = 12.6 Hz), 69.85 (d, J = 5.8 Hz), 24.18 (d, J = 4.1 Hz), 21.18 (d, J = 4.3 Hz). 31P NMR (162 MHz, CDCl3) δ 29.82 (s). HRMS (ESI): [M + H]+ calcd for C17H22O2P+ 289.1352; found 289.1353.
Isopropyl di-m-tolylphosphinate (3c) [41]. Colorless oil. Isolated yield: 80% (23.0 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 12.6 Hz, 2H), 7.61–7.56 (m, 2H), 7.41–7.24 (m, 4H), 4.69–4.61 (m, 1H), 2.37 (s, 6H), 1.35 (d, J = 6.2 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 138.22 (d, J = 13.0 Hz), 132.89 (s), 132.73 (d, J = 2.9 Hz), 132.13 (d, J = 10.1 Hz), 128.66 (d, J = 10.0 Hz), 128.29 (d, J = 13.8 Hz), 70.15 (d, J = 6.0 Hz), 24.33 (d, J = 4.2 Hz), 21.38 (s). 31P NMR (162 MHz, CDCl3) δ 30.62 (s). HRMS (ESI): [M + H]+ calcd for C17H22O2P+ 289.1352; found 289.1343.
Isopropyl di-p-tolylphosphinate (3d) [40]. Colorless oil. Isolated yield: 87% (25.0 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.69 (dd, J = 12.0, 8.0 Hz, 4H), 7.32–7.15 (m, 4H), 4.68–4.60 (m, 1H), 2.37 (s, 6H), 1.33 (d, J = 6.2 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 142.29 (d, J = 2.9 Hz), 131.62 (d, J = 10.4 Hz), 130.07 (s), 129.12 (d, J = 13.5 Hz), 128.68 (s), 69.90 (d, J = 6.0 Hz), 24.33 (d, J = 4.1 Hz), 21.59 (d, J = 1.0 Hz). 31P NMR (162 MHz, CDCl3) δ 30.77 (s). HRMS (ESI): [M + H]+ calcd for C17H22O2P+ 289.1352; found 289.1352.
Isopropyl bis(4-methoxyphenyl)phosphinate (3e) [42]. Colorless oil. Isolated yield: 80% (25.6 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.73 (dd, J = 11.5, 8.7 Hz, 4H), 6.94 (d, J = 6.7 Hz, 4H), 4.62 (td, J = 12.3, 6.2 Hz, 1H), 3.83 (s, 6H), 1.32 (d, J = 6.1 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 162.36 (d, J = 2.6 Hz), 133.47 (d, J = 11.3 Hz), 130.95 (s), 128.88–128.83 (m), 124.83 (s), 123.40 (s), 113.90 (d, J = 14.0 Hz), 69.68 (d, J = 5.6 Hz), 55.31 (s), 24.35 (d, J = 3.9 Hz). 31P NMR (162 MHz, CDCl3) δ 30.61 (s). HRMS (ESI): [M + H]+ calcd for C17H22O4P+ 321.1250; found 321.1249.
Isopropyl bis(4-(trifluoromethyl)phenyl)phosphinate (3f) [40]. Colorless oil. Isolated yield: 65% (25.7 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.96 (dd, J = 11.9, 8.0 Hz, 4H), 7.73 (dd, J = 8.1, 2.6 Hz, 4H), 4.81–4.66 (m, 1H), 1.39 (d, J = 6.2 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 135.95 (d, J = 135.7 Hz), 134.93–133.20 (m), 132.11 (d, J = 10.4 Hz), 126.01–125.08 (m), 123.47 (d, J = 272.6 Hz). 31P NMR (162 MHz, CDCl3) δ 25.96 (s). 19F NMR (376 MHz, CDCl3) δ -63.25 (d, J = 26.9 Hz). HRMS (ESI): [M + H]+ calcd for C17H16F6O2P+ 397.0787; found 397.0793.
Isopropyl di([1,1’-biphenyl]-4-yl)phosphinate (3g). Colorless oil. Isolated yield: 73% (30.1 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.95–7.90 (m, 4H), 7.67 (dd, J = 8.2, 3.1 Hz, 4H), 7.62–7.54 (m, 4H), 7.46–7.42 (m, 4H), 7.41–7.33 (m, 2H), 4.91–4.55 (m, 1H), 1.40 (d, J = 6.2 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 144.80 (d, J = 2.9 Hz), 140.04 (s), 132.18 (d, J = 10.4 Hz), 131.75 (s), 130.37 (s), 128.95 (s), 128.12 (s), 127.28 (d, J = 2.2 Hz), 127.14 (s), 70.41 (d, J = 6.0 Hz), 24.43 (d, J = 4.2 Hz). 31P NMR (162 MHz, CDCl3) δ 29.93 (s). HRMS (ESI): [M + H]+ calcd for C27H26O2P+ 413.1665; found 413.1660.
Isopropyl bis(4-ethyl formatephenyl)phosphinate (3h) [41]. Colorless oil. Isolated yield: 73% (29.5 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 8.11 (dd, J = 8.1, 3.1 Hz, 4H), 7.90 (dd, J = 11.9, 8.2 Hz, 4H), 4.83–4.62 (m, 1H), 3.93 (s, 6H), 1.37 (d, J = 6.2 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 166.16 (s), 137.32 (s), 135.98 (s), 133.43 (d, J = 2.9 Hz), 131.66 (d, J = 10.4 Hz), 129.52 (d, J = 13.2 Hz), 71.20 (d, J = 6.0 Hz), 52.46 (s), 24.27 (d, J = 4.2 Hz). 31P NMR (162 MHz, CDCl3) δ 27.23 (s). HRMS (ESI): [M + H]+ calcd for C21H26O6P+ 405.1462; found 405.1466.
Isopropyl bis(4-acetylphenyl)phosphinate (3i) [41]. Colorless oil. Isolated yield: 81% (27.9 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 8.09–7.97 (m, 4H), 7.93 (dd, J = 11.6, 8.0 Hz, 4H), 4.88–4.51 (m, 1H), 2.63 (s, 6H), 1.38 (d, J = 6.2 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 197.42 (s), 139.72 (d, J = 2.8 Hz), 137.37 (s), 136.03 (s), 131.93 (d, J = 10.3 Hz), 128.16 (d, J = 13.2 Hz), 71.30 (d, J = 6.1 Hz), 26.79 (s), 24.28 (d, J = 4.2 Hz). 31P NMR (162 MHz, CDCl3) δ 27.00 (s). HRMS (ESI): [M + H]+ calcd for C19H22O4P+ 345.1250; found 345.1246.
Isopropyl bis(4-cyanophenyl)phosphinate (3j). Colorless oil. Isolated yield: 84% (26.0 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.95–7.90 (m, 4H), 7.84–7.68 (m, 4H), 4.84–4.64 (m, 1H), 1.39 (d, J = 6.2 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 137.34 (s), 135.99 (s), 132.34 (s), 132.20 (d, J = 0.8 Hz), 132.10 (s), 117.66 (d, J = 1.3 Hz), 116.24 (d, J = 3.2 Hz), 72.15 (d, J = 6.0 Hz), 24.26 (d, J = 4.2 Hz). 31P NMR (162 MHz, CDCl3) δ 24.54 (s). HRMS (ESI): [M + H]+ calcd for C17H16N2O2P+ 311.0944; found 311.0944.
Isopropyl bis(4-formylphenyl)phosphinate (3k). Colorless oil. Isolated yield: 63% (19.9 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 10.08 (s, 2H), 8.16–7.79 (m, 8H), 4.76 (qd, J = 12.4, 6.2 Hz, 1H), 1.39 (d, J = 6.2 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 191.58 (s), 138.70 (d, J = 2.6 Hz), 137.38 (s), 132.30 (d, J = 10.3 Hz), 129.56 (d, J = 13.3 Hz), 71.62 (d, J = 6.1 Hz), 24.33 (d, J = 4.2 Hz). 31P NMR (162 MHz, CDCl3) δ 26.27 (s). HRMS (ESI): [M + H]+ calcd for C17H18O4P+ 317.0937; found 317.0943.
Isopropyl bis(4-vinylphenyl)phosphinate (3l). Colorless oil. Isolated yield: 58% (18.1 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.76 (dt, J = 18.5, 9.3 Hz, 4H), 7.46 (dd, J = 8.1, 2.9 Hz, 4H), 6.72 (dd, J = 17.6, 10.9 Hz, 2H), 5.83 (d, J = 17.6 Hz, 2H), 5.36 (d, J = 10.9 Hz, 2H), 4.67 (qd, J = 12.3, 6.1 Hz, 1H), 1.35 (d, J = 6.1 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 141.01 (d, J = 2.9 Hz), 136.01 (s), 131.93 (d, J = 10.4 Hz), 126.18 (d, J = 13.5 Hz), 116.40 (s), 70.27 (d, J = 5.9 Hz), 24.35 (d, J = 4.1 Hz). 31P NMR (162 MHz, CDCl3) δ 29.63 (s). HRMS (ESI): [M + H]+ calcd for C19H22O2P+ 313.1352; found 313.1350.
Isopropyl di(naphthalen-1-yl)phosphinate (3m). White solid. Isolated yield: 80% (28.8 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 8.64–8.52 (m, 2H), 8.22–8.16 (m, 2H), 8.00 (d, J = 8.2 Hz, 2H), 7.89–7.80 (m, 2H), 7.54–7.42 (m, 6H), 4.90–4.77 (m, 1H), 1.34 (d, J = 6.2 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 134.05 (d, J = 10.2 Hz), 133.69 (d, J = 10.7 Hz), 133.41 (d, J = 3.1 Hz), 132.98 (d, J = 10.5 Hz), 129.27 (s), 128.85 (d, J = 1.5 Hz), 127.15 (s), 126.81 (d, J = 4.9 Hz), 126.25 (s), 124.65 (d, J = 14.8 Hz), 70.95 (d, J = 6.0 Hz), 24.33 (d, J = 4.2 Hz). 31P NMR (162 MHz, CDCl3) δ 32.00 (s). HRMS (ESI): [M + H]+ calcd for C23H22O2P+ 361.1352; found 361.1349.
Isopropyl bis(1,2-dihydroacenaphthylen-5-yl)phosphinate (3n). White solid. Isolated yield: 71% (29.3 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 8.14 (dd, J = 16.1, 7.9 Hz, 4H), 7.42 (dd, J = 8.3, 7.1 Hz, 2H), 7.35–7.21 (m, 4H), 4.82–4.74 (m, 1H), 3.36 (s, 8H), 1.34 (d, J = 6.2 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 152.00 (d, J = 3.0 Hz), 146.44 (d, J = 1.8 Hz), 139.27 (d, J = 11.9 Hz), 135.66 (d, J = 11.4 Hz), 131.41 (d, J = 11.0 Hz), 128.93 (s), 124.69 (s), 123.33 (s), 122.27 (d, J = 3.5 Hz), 119.93 (s), 118.52 (d, J = 14.8 Hz), 70.33 (d, J = 5.9 Hz), 30.32 (d, J = 12.9 Hz), 24.44 (d, J = 4.2 Hz). 31P NMR (162 MHz, CDCl3) δ 29.36 (s). HRMS (ESI): [M + H]+ calcd for C27H26O2P+ 413.1665; found 413.1652.
Isopropyl bis(1,2-dihydroacenaphthylen-5-yl)phosphinate (3o). White solid. Isolated yield: 79% (21.5 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.70–7.68 (m, 2H), 7.65 (dd, J = 7.8, 3.6 Hz, 2H), 7.19–7.12 (m, 2H), 4.82–4.53 (m, 1H), 1.38 (d, J = 6.2 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 136.26 (d, J = 12.1 Hz), 133.93 (s), 133.53 (d, J = 6.4 Hz), 132.31 (s), 128.16 (d, J = 16.5 Hz), 71.41 (d, J = 5.9 Hz), 24.29 (d, J = 4.3 Hz). 31P NMR (162 MHz, CDCl3) δ 16.86 (s). HRMS (ESI): [M + H]+ calcd for C11H14O2PS2+ 273.0167; found 273.0164.
Isopropyl bis(benzo[b]thiophen-5-yl)phosphinate (3p). Colorless oil. Isolated yield: 80% (29.8 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 8.38 (d, J = 13.3 Hz, 2H), 7.93 (dd, J = 8.3, 2.9 Hz, 2H), 7.76–7.71 (m, 2H), 7.49 (d, J = 5.5 Hz, 2H), 7.39 (d, J = 5.5 Hz, 2H), 4.78–4.69 (m, 1H), 1.39 (d, J = 6.2 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 143.28 (d, J = 2.9 Hz), 139.24 (d, J = 14.9 Hz), 128.97 (s), 127.87 (d, J = 10.7 Hz), 127.68 (s), 126.16 (d, J = 11.6 Hz), 124.21 (s), 122.73 (d, J = 14.2 Hz), 70.39 (d, J = 5.9 Hz), 24.42 (d, J = 4.1 Hz). 31P NMR (162 MHz, CDCl3) δ 31.23 (s). HRMS (ESI): [M + H]+ calcd for C19H18O2PS2+ 373.0480; found 373.0474.
Isopropyl di(benzofuran-5-yl)phosphinate (3q). Colorless oil. Isolated yield: 89% (30.3 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 8.16 (dd, J = 12.6, 0.8 Hz, 2H), 7.78–7.73 (m, 2H), 7.67 (d, J = 2.2 Hz, 2H), 7.56 (dd, J = 8.5, 2.4 Hz, 2H), 6.84–6.74 (m, 2H), 4.84–4.55 (m, 1H), 1.37 (d, J = 6.2 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 156.76 (d, J = 3.1 Hz), 146.11 (s), 127.68 (d, J = 7.3 Hz), 127.54 (d, J = 12.2 Hz), 126.32 (s), 125.92 (d, J = 11.6 Hz), 111.70 (d, J = 14.7 Hz), 106.86 (d, J = 1.0 Hz), 70.15 (d, J = 5.9 Hz), 24.38 (d, J = 4.2 Hz). 31P NMR (162 MHz, CDCl3) δ 31.47 (s). HRMS (ESI): [M + H]+ calcd for C19H18O4P+ 341.0937; found 341.0932
Isopropyl bis(benzo[d][1,3]dioxol-5-yl)phosphinate (3r). Colorless oil. Isolated yield: 60% (20.9 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.35 (dd, J = 12.9, 7.9 Hz, 1H), 7.19 (d, J = 11.8 Hz, 1H), 6.86 (dd, J = 7.9, 2.7 Hz, 1H), 6.00 (s, 1H), 4.76–4.53 (m, 1H), 1.34 (d, J = 6.2 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 150.76 (d, J = 3.1 Hz), 147.80 (d, J = 19.8 Hz), 127.02 (d, J = 11.1 Hz), 125.71 (d, J = 143.5 Hz), 111.01 (d, J = 12.6 Hz), 108.59 (d, J = 16.4 Hz), 101.52 (s), 70.15 (d, J = 5.9 Hz), 24.31 (d, J = 4.1 Hz). 31P NMR (162 MHz, CDCl3) δ 29.58 (s). HRMS (ESI): [M + H]+ calcd for C17H18O6P+ 349.0836; found 349.0828.
Isopropyl di(quinolin-5-yl)phosphinate (3s). White solid. Isolated yield: 67% (24.3 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 8.96 (dd, J = 12.8, 5.8 Hz, 4H), 8.31 (d, J = 8.5 Hz, 2H), 8.16 (dd, J = 15.2, 7.1 Hz, 2H), 7.77 (td, J = 7.9, 3.3 Hz, 2H), 7.43 (dd, J = 8.6, 4.2 Hz, 2H), 4.88 (qd, J = 12.4, 6.2 Hz, 1H), 1.37 (d, J = 6.2 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 150.86 (s), 148.26 (d, J = 10.7 Hz), 135.06 (d, J = 3.0 Hz), 134.71 (d, J = 4.7 Hz), 134.02 (d, J = 9.8 Hz), 129.90 (d, J = 211.1 Hz), 129.79 (s), 128.59–128.38 (m), 128.28 (d, J = 15.6 Hz), 122.03 (s), 71.61 (d, J = 6.0 Hz), 24.35 (d, J = 4.2 Hz). 31P NMR (162 MHz, CDCl3) δ 29.37 (s). HRMS (ESI): [M + H]+ calcd for C21H20N2O2P+ 363.1257; found 363.1252.
Isopropyl di(indolin-4-yl)phosphinate (3t). Colorless oil. Isolated yield: 74% (25.3 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 8.26 (dd, J = 8.3, 2.7 Hz, 2H), 7.73–7.52 (m, 4H), 4.62 (qd, J = 12.3, 6.1 Hz, 1H), 4.26 (t, J = 8.3 Hz, 4H), 3.15 (t, J = 8.2 Hz, 4H), 1.33 (d, J = 6.2 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 177.11 (s), 147.91 (d, J = 3.0 Hz), 131.64 (d, J = 11.0 Hz), 131.12 (d, J = 14.3 Hz), 127.57 (d, J = 11.2 Hz), 127.08 (d, J = 141.4 Hz),117.88 (d, J = 13.8 Hz), 69.86 (d, J = 5.9 Hz), 49.70 (s), 40.39 (s), 28.98 (s), 24.37 (d, J = 4.1 Hz). 31P NMR (162 MHz, CDCl3) δ 30.50 (s). HRMS (ESI): [M + H]+ calcd for C19H24N2O2P+ 343.1570; found 343.1572.
Isopropyl di(9H-carbazol-1-yl)phosphinate (3u). White solid. Isolated yield: 73% (32.0 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 10.26 (s, 2H), 8.21 (d, J = 7.7 Hz, 2H), 8.06 (d, J = 7.8 Hz, 2H), 7.72 (dd, J = 13.1, 7.5 Hz, 2H), 7.51 (d, J = 8.1 Hz, 2H), 7.45 (t, J = 7.3 Hz, 2H), 7.24 (dd, J = 9.6, 5.0 Hz, 4H), 4.74 (ddt, J = 12.3, 8.9, 6.2 Hz, 1H), 1.42 (d, J = 6.1 Hz,6H). 13C NMR (101 MHz, CDCl3) δ 141.97 (d, J = 6.1 Hz), 139.73 (s), 128.73 (d, J = 8.3 Hz), 126.65 (s), 124.63 (d, J = 2.6 Hz), 124.26 (d, J = 9.5 Hz), 122.27 (s), 120.41 (s), 119.77 (s), 118.83 (d, J = 12.5 Hz), 111.64 (d, J = 142.4 Hz), 111.24 (s), 71.40 (d, J = 6.1 Hz), 24.43 (d, J = 4.2 Hz). 31P NMR (162 MHz, CDCl3) δ 35.30 (s). HRMS (ESI): [M + H]+ calcd for C27H24N2O2P+ 439.1570; found 439.1567.
Isopropyl bis(8-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)phosphinate (3v). White solid. Isolated yield: 81% (32.1 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 8.38 (dd, J = 12.8, 1.0 Hz, 2H), 8.08–7.85 (m, 2H), 7.36 (dd, J = 7.8, 2.9 Hz, 2H), 4.68 (qd, J = 12.3, 6.2 Hz, 1H), 3.00 (t, J = 5.9 Hz, 4H), 2.83–2.44 (m, 4H), 2.28–1.94 (m, 4H), 1.36 (d, J = 6.2 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 197.24 (s), 148.35 (d, J = 2.6 Hz), 135.94 (d, J = 10.5 Hz), 135.01 (d, J = 140.4Hz), 132.55 (d, J = 12.5 Hz), 130.66 (d, J = 11.4 Hz), 129.36 (d, J = 12.5 Hz), 70.81 (d, J = 6.0 Hz), 39.04 (s), 29.82 (s), 24.35 (d, J = 4.1 Hz), 22.79 (s). 31P NMR (162 MHz, CDCl3) δ 27.82 (s). HRMS (ESI): [M + H]+ calcd for C23H26O4P+ 397.1563; found 397.1561.
Isopropyl bis(1-oxo-2,3-dihydro-1H-inden-4-yl)phosphinate (3w). Colorless oil. Isolated yield: 89% (32.8 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 8.18 (dd, J = 12.4, 7.4 Hz, 2H), 7.95 (d, J = 7.6 Hz, 2H), 7.56 (dd, J = 7.3, 6.0 Hz, 2H), 4.85 (dq, J = 12.5, 6.2 Hz, 1H), 3.22 (dt, J = 17.9, 5.7 Hz, 2H), 3.08 (dt, J = 11.5, 5.6 Hz, 2H), 2.64 (t, J = 5.9 Hz, 4H), 1.41 (d, J = 6.1 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 205.78 (s), 157.64 (d, J = 11.6 Hz), 138.41 (d, J = 9.8 Hz), 137.99 (d, J = 11.1 Hz), 129.95 (d, J = 135.7 Hz), 127.95 (d, J = 2.7 Hz), 127.59 (d, J = 11.6 Hz), 71.30 (d, J = 5.9 Hz), 35.86 (s), 26.12 (d, J = 2.2 Hz), 24.37 (d, J = 4.1 Hz). 31P NMR (162 MHz, CDCl3) δ 24.53 (s). HRMS (ESI): [M + H]+ calcd for C21H22O4P+ 369.1250; found 369.1250.
Ethyl diphenylphosphinate (4a) [40]. Colorless oil. Isolated yield: 91% (22.4 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.88–7.77 (m, 4H), 7.55–7.48 (m, 2H), 7.48–7.41 (m, 4H), 4.11 (p, J = 7.1 Hz, 2H), 1.37 (t, J = 7.0 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 132.11 (d, J = 2.7 Hz), 131.68 (d, J = 137.4 Hz), 131.63 (d, J = 10.1 Hz), 128.52 (d, J = 13.1 Hz), 61.12 (d, J = 5.9 Hz), 16.52 (d, J = 6.7 Hz). 31P NMR (162 MHz, CDCl3) δ 31.33 (s). HRMS (ESI): [M + H]+ calcd for C14H16O2P+ 247.0882; found 247.0892.
Octyl diphenylphosphinate (4b) [42]. White solid. Isolated yield: 92% (30.4 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.89–7.77 (m, 4H), 7.55–7.47 (m, 2H), 7.44 (dt, J = 8.5, 4.5 Hz, 4H), 4.03 (q, J = 6.6 Hz, 2H), 1.79–1.66 (m, 2H), 1.38 (d, J = 6.6 Hz, 2H), 1.26 (d, J = 3.3 Hz, 8H), 0.87 (t, J = 6.5 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 132.08 (d, J = 2.7 Hz), 131.63 (d, J = 10.1 Hz), 131.60 (d, J = 138.3 Hz), 128.50 (d, J = 13.1 Hz), 65.06 (d, J = 6.1 Hz), 31.75 (s), 30.52 (d, J = 6.6 Hz), 29.12 (d, J = 5.1 Hz), 27.27 (s), 25.60 (s), 22.62 (s), 14.10 (s). 31P NMR (162 MHz, CDCl3) δ 31.22 (s). HRMS (ESI): [M + H]+ calcd for C20H28O2P+ 331.1821; found 331.1821.
Neopentyl diphenylphosphinate (4c) [42]. White solid. Isolated yield: 77% (22.2 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.82 (dd, J = 12.2, 7.2 Hz, 4H), 7.56–7.49 (m, 2H), 7.45 (dt, J = 10.2, 5.2 Hz, 4H), 3.67 (d, J = 4.8 Hz, 2H), 0.99 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 132.07 (d, J = 2.8 Hz), 131.69 (d, J = 137.4 Hz), 131.66 (d, J = 10.0 Hz), 128.52 (d, J = 13.1 Hz), 73.84 (d, J = 6.5 Hz), 32.26 (d, J = 7.4 Hz), 26.28 (s). 31P NMR (162 MHz, CDCl3) δ 30.62 (s). HRMS (ESI): [M + H]+ calcd for C17H22O2P+ 289.1352; found 289.1351.
Cyclopropylmethyl diphenylphosphinate (4d). Colorless oil. Isolated yield: 85% (23.1 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.90–7.77 (m, 4H), 7.51 (dd, J = 10.5, 4.2 Hz, 2H), 7.48–7.37 (m, 4H), 3.89 (t, J = 7.4 Hz, 2H), 1.18 (ddd, J = 10.2, 7.8, 4.0 Hz, 1H), 0.54 (q, J = 5.2 Hz, 2H), 0.26 (q, J = 5.1 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 132.21 (d, J = 2.8 Hz), 131.72 (d, J = 10.2 Hz), 131.46 (d, J = 137.4Hz), 128.53 (d, J = 13.2 Hz), 71.73 (d, J = 6.7 Hz), 63.74 (d, J = 5.9 Hz), 58.95 (s). 31P NMR (162 MHz, CDCl3) δ 31.09 (s). HRMS (ESI): [M + H]+ calcd for C16H18O2P+ 273.1039; found 273.0996.
Cyclobutyl diphenylphosphinate (4e). Colorless oil. Isolated yield: 59% (16.0 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.87–7.74 (m, 4H), 7.55–7.47 (m, 2H), 7.48–7.35 (m, 4H), 4.91–4.67 (m, 1H), 2.23 (dd, J = 17.1, 8.6 Hz, 4H), 1.81–1.63 (m, 1H), 1.53–1.36 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 132.06 (d, J = 2.8 Hz), 131.96 (d, J = 137.4 Hz), 131.63 (d, J = 10.2 Hz), 128.45 (d, J = 13.1 Hz), 69.17 (d, J = 7.5 Hz), 32.35 (d, J = 4.5 Hz), 12.86 (s). 31P NMR (162 MHz, CDCl3) δ 29.67 (s). HRMS (ESI): [M + H]+ calcd for C16H18O2P+ 273.1039, found 273.1034.
Cyclohexyl diphenylphosphinate (4f) [40]. Colorless oil. Isolated yield: 84% (25.2 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.88–7.74 (m, 4H), 7.54–7.47 (m, 2H), 7.43 (ddd, J = 7.1, 5.5, 2.7 Hz, 4H), 4.53–4.34 (m, 1H), 1.99–1.82 (m, 2H), 1.74 (dd, J = 10.1, 4.8 Hz, 2H), 1.60 (dt, J = 12.6, 6.3 Hz, 2H), 1.47 (dd, J = 9.5, 4.1 Hz, 1H), 1.37–1.25 (m, 3H). 13C NMR (101 MHz, CDCl3) δ 133.26 (s), 131.92 (d, J = 2.8 Hz), 131.62 (d, J = 10.1 Hz), 128.41 (d, J = 13.1 Hz), 74.97 (d, J = 6.2 Hz), 33.95 (d, J = 3.7 Hz), 25.21 (s), 23.60 (s). 31P NMR (162 MHz, CDCl3) δ 29.78 (s). HRMS (ESI): [M + H]+ calcd for C18H22O2P+ 301.1352; found 301.1350.
Pentan-3-yl diphenylphosphinate (4g). Colorless oil. Isolated yield: 66% (19.0 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.89–7.75 (m, 4H), 7.55–7.47 (m, 2H), 7.43 (td, J = 7.3, 3.4 Hz, 4H), 4.49–4.29 (m, 1H), 1.79–1.59 (m, 4H), 0.88 (t, J = 7.4 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 132.69 (d, J = 137.4 Hz), 131.87 (d, J = 2.7 Hz), 131.64 (d, J = 10.1 Hz), 128.36 (d, J = 13.1 Hz), 79.28 (d, J = 6.6 Hz), 27.28 (d, J = 3.8 Hz), 9.13 (s). 31P NMR (162 MHz, CDCl3) δ 29.45 (s). HRMS (ESI): [M + H]+ calcd for C17H22O2P+ 289.1352; found 289.1349.
2-Methoxyethyl diphenylphosphinate (4i). Colorless oil. Isolated yield: 83% (22.9 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.91–7.78 (m, 4H), 7.51 (dd, J = 10.5, 4.0 Hz, 2H), 7.45 (td, J = 7.3, 3.4 Hz, 4H), 4.18 (td, J = 7.5, 4.8 Hz, 2H), 3.79–3.56 (m, 2H), 3.36 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 132.07 (d, J = 2.8 Hz), 131.83 (d, J = 137.4 Hz), 131.67 (d, J = 10.1 Hz), 128.49 (d, J = 13.1 Hz), 69.87 (d, J = 5.8 Hz), 11.48 (d, J = 7.2 Hz), 3.58 (s). 31P NMR (162 MHz, CDCl3) δ 32.41 (s). HRMS (ESI): [M + H]+ calcd for C15H18O3P+ 277.0988; found 277.0990.
3-Chloropropyl diphenylphosphinate (4j). Colorless oil. Isolated yield: 76% (22.3 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.88–7.75 (m, 4H), 7.57–7.50 (m, 2H), 7.46 (ddd, J = 7.1, 5.6, 2.8 Hz, 4H), 4.19 (dd, J = 12.9, 5.9 Hz, 2H), 3.71 (t, J = 6.3 Hz, 2H), 2.23–2.13 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 132.32 (d, J = 2.8 Hz), 131.63 (d, J = 10.1 Hz), 131.20 (d, J = 137.4 Hz), 128.64 (d, J = 13.2 Hz), 61.52 (d, J = 5.7 Hz), 40.98 (s), 33.38 (d, J = 6.5 Hz). 31P NMR (162 MHz, CDCl3) δ 32.07 (s). HRMS (ESI): [M + H]+ calcd for C15H17ClO2P+ 295.0649; found 295.0652.
Pent-4-en-1-yl diphenylphosphinate (4k). Colorless oil. Isolated yield: 56% (16.0 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.81 (dd, J = 11.4, 7.7 Hz, 4H), 7.58–7.49 (m, 2H), 7.45 (dt, J = 10.2, 5.1 Hz, 4H), 5.67–5.47 (m, 1H), 5.48–5.28 (m, 1H), 4.02 (qd, J = 6.9, 3.1 Hz, 2H), 2.45 (dq, J = 31.7, 6.8 Hz, 2H), 1.65 (d, J = 6.2 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 132.11 (d, J = 2.6 Hz), 131.68 (d, J = 10.1 Hz), 128.51 (d, J = 13.1 Hz), 128.35 (s), 125.99 (s), 64.57 (d, J = 6.1 Hz), 33.93 (d, J = 6.6 Hz), 18.05 (s). 31P NMR (162 MHz, CDCl3) δ 31.24 (s). HRMS (ESI): [M + H]+ calcd for C17H20O2P+ 287.1195; found 287.1200.
4,4,4-Trifluorobutyl diphenylphosphinate (4l). Colorless oil. Isolated yield: 67% (22.0 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.88–7.73 (m, 4H), 7.55 (t, J = 7.4 Hz, 2H), 7.47 (td, J = 7.3, 3.5 Hz, 4H), 4.09 (dd, J = 12.7, 6.3 Hz, 2H), 2.34–2.21 (m, 2H), 1.99 (dt, J = 16.1, 6.1 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 132.38 (d, J = 2.8 Hz), 131.58 (d, J = 10.2 Hz), 131.12 (d, J = 137.4 Hz), 128.67 (d, J = 13.2 Hz), 63.09 (d, J = 5.7 Hz), 30.49 (q, J = 29.3 Hz), 23.44 (dd, J = 6.6, 3.1 Hz). 31P NMR (162 MHz, CDCl3) δ 32.18 (s). 19F NMR (376 MHz, CDCl3) δ -66.29 (s). HRMS (ESI): [M + H]+ calcd for C16H17F3O2P+ 329.0913; found 329.0908.
2-((Diphenylphosphoryl)oxy)ethyl pivalate (4m). Colorless oil. Isolated yield: 38% (13.1 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.88–7.74 (m, 4H), 7.57–7.50 (m, 2H), 7.46 (td, J = 7.4, 3.5 Hz, 4H), 4.38–4.30 (m, 2H), 4.26–4.19 (m, 2H), 1.21 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 178.30 (s), 132.34 (d, J = 2.7 Hz), 131.63 (d, J = 10.2 Hz), 131.15 (d, J = 137.4Hz), 128.61 (d, J = 13.2 Hz), 63.17 (d, J = 7.7 Hz), 62.51 (d, J = 5.6 Hz), 38.78 (s), 27.13 (d, J = 6.4 Hz). 31P NMR (162 MHz, CDCl3) δ 32.39 (s). HRMS (ESI): [M + H]+ calcd for C19H24O4P+ 347.1407; found 347.1403.
2-(Methylthio)ethyl diphenylphosphinate (4n). Colorless oil. Isolated yield: 64% (18.7 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.84 (dd, J = 11.9, 7.6 Hz, 4H), 7.58–7.50 (m, 2H), 7.47 (dd, J = 7.1, 3.0 Hz, 4H), 4.17 (dd, J = 14.2, 7.1 Hz, 2H), 2.83 (t, J = 6.8 Hz, 2H), 2.10 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 132.30 (d, J = 2.8 Hz), 131.68 (d, J = 10.2 Hz), 131.26 (d, J = 137.4 Hz), 128.61 (d, J = 13.2 Hz), 63.38 (d, J = 5.8 Hz), 34.38 (d, J = 6.8 Hz), 15.83 (s). 31P NMR (162 MHz, CDCl3) δ 32.04 (s). HRMS (ESI): [M + H]+ calcd for C15H18O2PS+ 293.0760; found 293.0757.
(Tetrahydrofuran-2-yl)methyl diphenylphosphinate (4o). Colorless oil. Isolated yield: 70% (21.1 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.92–7.73 (m, 4H), 7.51 (d, J = 6.8 Hz, 2H), 7.45 (s, 4H), 4.25–4.14 (m, 1H), 4.04 (d, J = 4.8 Hz, 1H), 4.00–3.91 (m, 2H), 3.90–3.76 (m, 1H), 2.03–1.95 (m, 1H), 1.93–1.84 (m, 1H), 1.76–1.67 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 132.21 (s), 131.75 (dd, J = 10.0, 5.8 Hz), 128.55 (d, J = 13.0 Hz), 68.56 (s), 66.55 (d, J = 5.9 Hz), 27.84 (s), 25.73 (s). 31P NMR (162 MHz, CDCl3) δ 32.21 (s). HRMS (ESI): [M + H]+ calcd for C17H20O3P+ 303.1145; found 303.1144.
(R)-(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl diphenylphosphinate (4p). Colorless oil. Isolated yield: 45% (19.4 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.83 (dd, J = 10.8, 8.7 Hz, 4H), 7.58–7.50 (m, 2H), 7.47 (dd, J = 7.3, 3.1 Hz, 4H), 4.44–4.35 (m, 1H), 4.13–4.07 (m, 1H), 4.07–3.98 (m, 2H), 3.89 (dd, J = 8.4, 5.6 Hz, 1H), 1.38 (d, J = 17.0 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 132.37 (d, J = 2.8 Hz), 131.75 (d, J = 4.0 Hz), 131.65 (d, J = 4.0 Hz), 128.62 (d, J = 13.2 Hz), 109.83 (s), 74.46 (d, J = 7.5 Hz), 66.24 (s), 64.85 (d, J = 5.9 Hz), 26.71 (s), 25.27 (s). 31P NMR (162 MHz, CDCl3) δ 32.76 (s). HRMS (ESI): [M + H]+ calcd for C18H22O4P+ 333.1250; found 333.1251.
(9H-Xanthen-9-yl)methyl diphenylphosphinate (4q). White solid. Isolated yield: 68% (28.0 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.60–7.40 (m, 6H), 7.33 (ddd, J = 6.9, 5.4, 2.6 Hz, 4H), 7.30–7.20 (m, 4H), 7.15–7.02 (m, 4H), 4.33 (t, J = 5.7 Hz, 1H), 4.07 (t, J = 5.5 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 152.49 (s), 132.05 (d, J = 2.8 Hz), 131.53 (d, J = 10.2 Hz), 131.04 (d, J = 137.4 Hz), 129.43 (s), 128.54 (s), 128.41 (s), 123.31 (s), 121.17 (s), 116.50 (s), 69.59 (d, J = 6.2 Hz), 40.26 (d, J = 8.1 Hz). 31P NMR (162 MHz, CDCl3) δ 31.81 (s). HRMS (ESI): [M + H]+ calcd for C26H22O3P+ 413.1301; found 413.1302.
2-(4-Isobutylphenyl)propyl diphenylphosphinate (4r). White solid. Isolated yield: 69% (27.0 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.75–7.59 (m, 4H), 7.49 (t, J = 7.3 Hz, 2H), 7.44–7.33 (m, 4H), 7.10 (q, J = 8.2 Hz, 4H), 4.16–3.88 (m, 2H), 3.25–3.06 (m, 1H), 2.46 (d, J = 7.2 Hz, 2H), 1.95–1.78 (m, 1H), 1.35 (d, J = 7.0 Hz, 3H), 0.90 (d, J = 6.6 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 140.08 (d, J = 16.2 Hz), 132.05 (d, J = 2.6 Hz), 131.65 (t, J = 9.8 Hz), 129.17 (s), 128.46 (d, J = 13.1 Hz), 127.26 (s), 69.75 (d, J = 6.2 Hz), 45.05 (s), 40.15 (d, J = 7.3 Hz), 30.29 (s), 22.40 (d, J = 2.5 Hz), 17.59 (s). 31P NMR (162 MHz, CDCl3) δ 31.03 (s). HRMS (ESI): [M + H]+ calcd for C25H30O2P+ 393.1978; found 393.1984.
(S)-2-(7-Methoxynaphthalen-2-yl)propyl diphenylphosphinate (4s). White solid. Isolated yield: 77% (32.0 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.71–7.63 (m, 4H), 7.59 (dd, J = 11.0, 6.3 Hz, 3H), 7.44 (dd, J = 15.1, 7.6 Hz, 2H), 7.32 (ddd, J = 18.8, 9.2, 3.4 Hz, 5H), 7.17–7.10 (m, 2H), 4.22–4.09 (m, 2H), 3.91 (s, 3H), 3.40–3.25 (m, 1H), 1.42 (d, J = 7.0 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 157.47 (s), 138.00 (s), 133.59 (s), 132.05 (s), 131.73 (s), 131.62 (s), 131.52 (s), 130.72 (d, J = 26.9 Hz), 129.17 (s), 129.00 (s), 128.45 (dd, J = 13.1, 2.2 Hz), 126.93 (s), 126.56 (s), 125.90 (s), 118.90 (s), 105.56 (s), 69.68 (d, J = 6.2 Hz), 55.33 (s), 40.47 (d, J = 7.2 Hz), 17.66 (s). 31P NMR (162 MHz, CDCl3) δ 31.26 (s). HRMS (ESI): [M + H]+ calcd for C26H26O3P+ 417.1614; found 417.1612.
Adamantan-1-ylmethyl diphenylphosphinate (4t). White solid. Isolated yield: 82% (30.0 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.82 (dd, J = 12.0, 7.2 Hz, 4H), 7.56–7.48 (m, 2H), 7.45 (dt, J = 10.1, 5.1 Hz, 4H), 3.57 (d, J = 4.9 Hz, 2H), 2.00 (s, 3H), 1.73 (d, J = 12.1 Hz, 3H), 1.65 (d, J = 12.0 Hz, 3H), 1.59 (s, 6H). 13C NMR (101 MHz, CDCl3) δ 132.05 (d, J = 2.8 Hz), 131.71 (d, J = 10.0 Hz), 131.71 (d, J = 138.4 Hz), 128.52 (d, J = 13.1 Hz), 74.16 (d, J = 6.5 Hz), 39.09 (s), 36.96 (s), 34.01 (d, J = 7.4 Hz), 28.03 (s). 31P NMR (162 MHz, CDCl3) δ 30.79 (s). HRMS (ESI): [M + H]+ calcd for C23H28O2P+ 367.1821; found 367.1816.
2-(1H-indol-2-yl)ethyl diphenylphosphinate (4u). Colorless oil. Isolated yield: 64% (23.1 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 8.42 (s, 1H), 7.81–7.69 (m, 4H), 7.53–7.44 (m, 3H), 7.44–7.35 (m, 4H), 7.30 (d, J = 34.1 Hz, 1H), 7.17 (t, J = 7.5 Hz, 1H), 7.06 (t, J = 7.4 Hz, 1H), 7.01 (s, 1H), 4.28 (q, J = 7.1 Hz, 2H), 3.20 (t, J = 7.1 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 136.20 (s), 132.13 (d, J = 2.6 Hz), 131.67 (d, J = 10.1 Hz), 130.75 (s), 128.52 (d, J = 13.1 Hz), 127.43 (s), 122.23 (d, J = 46.2 Hz), 119.02 (d, J = 63.8 Hz), 111.23 (s), 65.02 (d, J = 6.2 Hz), 26.82 (d, J = 6.9 Hz). 31P NMR (162 MHz, CDCl3) δ 31.70 (s). HRMS (ESI): [M + H]+ calcd for C22H21NO2P+ 362.1304; found 362.1294.
3-(1,3-Dioxoisoindolin-2-yl)propyl diphenylphosphinate (4v). White solid. Isolated yield: 83% (33.6 mg); (eluent: petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, CDCl3) δ 7.89–7.73 (m, 6H), 7.69 (dd, J = 5.3, 3.1 Hz, 2H), 7.54–7.46 (m, 2H), 7.43 (td, J = 7.3, 3.5 Hz, 4H), 4.10 (q, J = 6.2 Hz, 2H), 3.88 (t, J = 6.9 Hz, 2H), 2.13 (p, J = 6.4 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 168.22 (s), 133.99 (s), 132.18 (d, J = 2.8 Hz), 132.01 (s), 131.64 (d, J = 10.2 Hz), 131.22 (d, J = 137.4 Hz), 128.55 (d, J = 13.2 Hz), 123.22 (s), 62.21 (d, J = 5.7 Hz), 34.93 (s), 29.47 (d, J = 6.7 Hz). 31P NMR (162 MHz, CDCl3) δ 31.87 (s). HRMS (ESI): [M + H]+ calcd for C23H21NO4P+ 406.1203; found 406.1204.

Supplementary Materials

The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/molecules30071564/s1: Table S1: Reaction condition optimization; Derivatization reaction of 3a; Characterization data of all products; and Scanned 1H NMR, 13C NMR, 31P NMR, and 19F NMR spectra of all products.

Author Contributions

Conceptualization and methodology, J.Y. and S.Y.; formal analysis, D.Q. and J.Y.; writing—original draft preparation, J.Y.; writing—review and editing, G.W. and S.Y All authors have read and agreed to the published version of the manuscript.

Funding

We are grateful to the NSFC (No. 22371105 and 22171119) for financial support.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Data are contained within the article and Supplementary Materials.

Conflicts of Interest

The authors declare no conflicts of interest.

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Molecules 30 01564 sch001
Scheme 1. Synthesis of diarylphosphinate compounds.
Scheme 1. Synthesis of diarylphosphinate compounds.
Molecules 30 01564 sch001
Molecules 30 01564 sch002
Scheme 2. Expansion of aryl halide substrates a. a Aryl halide 1 (0.2 mmol), sodium hypophosphite (0.4 mmol), isopropyl alcohol 2a (1.6 mmol), PivCl (0.8 mmol), Pd(dppf)Cl2 (2.5 mol%), DABCO (0.6 mmol), PhMe (2.0 mL) under Ar at 100 °C for 28 h. b Under Ar at 120 °C for 28 h.
Scheme 2. Expansion of aryl halide substrates a. a Aryl halide 1 (0.2 mmol), sodium hypophosphite (0.4 mmol), isopropyl alcohol 2a (1.6 mmol), PivCl (0.8 mmol), Pd(dppf)Cl2 (2.5 mol%), DABCO (0.6 mmol), PhMe (2.0 mL) under Ar at 100 °C for 28 h. b Under Ar at 120 °C for 28 h.
Molecules 30 01564 sch002
Molecules 30 01564 sch003
Scheme 3. Expansion of alcohol substrates a. a Bromobenzene 1a (0.2 mmol), sodium hypophosphite (0.4 mmol), alcohol 2 (1.6 mmol), PivCl (0.8 mmol), Pd(dppf)Cl2 (2.5 mol%), DABCO (0.6 mmol), PhMe (2.0 mL) under Ar at 100 °C for 28 h.
Scheme 3. Expansion of alcohol substrates a. a Bromobenzene 1a (0.2 mmol), sodium hypophosphite (0.4 mmol), alcohol 2 (1.6 mmol), PivCl (0.8 mmol), Pd(dppf)Cl2 (2.5 mol%), DABCO (0.6 mmol), PhMe (2.0 mL) under Ar at 100 °C for 28 h.
Molecules 30 01564 sch003
Molecules 30 01564 sch004
Scheme 4. Gram-scale reaction of 3a.
Scheme 4. Gram-scale reaction of 3a.
Molecules 30 01564 sch004
Molecules 30 01564 sch005
Scheme 5. Controlled experiment.
Scheme 5. Controlled experiment.
Molecules 30 01564 sch005
Molecules 30 01564 sch006
Scheme 6. Possible mechanisms.
Scheme 6. Possible mechanisms.
Molecules 30 01564 sch006
Table 1. Reaction condition optimization a.
Table 1. Reaction condition optimization a.
Molecules 30 01564 i001
EntryAdditiveBaseCat.Sol.Result/% b
1noneDABCOPd(dppf)Cl2PhMeN.R. g
2BzClDABCOPd(dppf)Cl2PhMeN.R. g
3TsClDABCOPd(dppf)Cl2PhMeN.R. g
4PivClDABCOPd(dppf)Cl2PhMe83
5PivClNaHCO3Pd(dppf)Cl2PhMe36
6PivClNaOAcPd(dppf)Cl2PhMetrace
7PivClDBU fPd(dppf)Cl2PhMe67
8PivClEt3N fPd(dppf)Cl2PhMe53
9PivClDIPEA fPd(dppf)Cl2PhMe60
10 cPivClDABCOPd(dppf)Cl2PhMe74
11 dPivClDABCOPd(dppf)Cl2PhMe80
12PivClDABCOPd(dppe)Cl2 ePhMe64
13PivClDABCOPd(PPh3)2Cl2 ePhMe16
14PivClDABCONi(dppf)Cl2PhMeN.R. g
15PivClDABCOCo(dppf)Cl2PhMeN.R. g
16PivClDABCOPd(dppf)Cl2THF51
17PivClDABCOPd(dppf)Cl2EtOAc63
18PivClDABCOPd(dppf)Cl2DCEtrace
a Bromobenzene (0.2 mmol), NaH2PO2 (0.4 mmol), isopropyl alcohol (1.6 mmol), additive (0.8 mmol), catalyst (2.5 mol%), DABCO (0.6 mmol), solvent (2.0 mL) under Ar at 100 °C for 28 h; b Isolated yield; c 1.0 mL solvent; d 3.0 mL solvent; e dppe = 1,2-Bis (diphenylphosphino) ethane; dppf = 1,1’-Bis (diphenylphosphino) ferrocene; PPh3 = triphenylphosphine; f DBU = 1,8-Diazabicyclo[5.4.0] undec-7-ene; Et3N = triethylamine; DIPEA = N,N-Diisopropylethylamine; DABCO = 1,4-Diazabicyclo[2.2.2] octane; g N.R.= No Reaction.
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Yang, J.; Qian, D.; Wang, G.; Yang, S. Pd-Catalyzed Direct Diarylation of Sodium Hypophosphite Enables the Synthesis of Diarylphosphonates. Molecules 2025, 30, 1564. https://doi.org/10.3390/molecules30071564

AMA Style

Yang J, Qian D, Wang G, Yang S. Pd-Catalyzed Direct Diarylation of Sodium Hypophosphite Enables the Synthesis of Diarylphosphonates. Molecules. 2025; 30(7):1564. https://doi.org/10.3390/molecules30071564

Chicago/Turabian Style

Yang, Jin, Dangwei Qian, Gangwei Wang, and Shangdong Yang. 2025. "Pd-Catalyzed Direct Diarylation of Sodium Hypophosphite Enables the Synthesis of Diarylphosphonates" Molecules 30, no. 7: 1564. https://doi.org/10.3390/molecules30071564

APA Style

Yang, J., Qian, D., Wang, G., & Yang, S. (2025). Pd-Catalyzed Direct Diarylation of Sodium Hypophosphite Enables the Synthesis of Diarylphosphonates. Molecules, 30(7), 1564. https://doi.org/10.3390/molecules30071564

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