Metal-Free Synthesis of Aryltriphenylphosphonium Bromides by the Reaction of Triphenylphosphine with Aryl Bromides in Refluxing Phenol.

A metal-free synthesis of aryltriphenylphosphonium bromides by the reaction of triphenylphosphine with aryl bromides in refluxing phenol is developed. This reaction tolerates hydroxymethyl, hydroxyphenyl, and carboxyl groups in aryl bromides, allowing to synthesize multifunctional aryltriphenylphosphonium bromides, from which facile access to multifunctional aryldiphenylphosphines and their oxides by hydrolysis and subsequent reduction is exemplified. A two-step addition-elimination mechanism, with the elimination step being a fast step, is also proposed.

Introduction

Aryltriphenylphosphonium salts have been widely used in organic synthesis as catalyst,[1−3] aryl source,[4] supporter,[5] and ionic liquid.[6] They can also be used in the preparation of hydrogen storage materials[7] and nonlinear optical chromophores.[8] [18F]-labeled aryltriphenylphosphonium as an imaging agent was employed for monitoring mitochondrial disease.[9] Four methods have emerged for the synthesis of aryltriphenylphosphonium salts by the reactions of Ph3P with (1) aryl radicals in situ generated by CoCl2-catalyzed reaction of Grignard reagents with aryl bromides (Scheme A),[10] (2) diazonium salts (Scheme B),[11] (3) aryl halides catalyzed by nickel (Scheme C),[12] and (4) aryl halides or pseudohalides catalyzed by palladium (Scheme D).[13−15] These methods require using either a metal catalyst or unstable, explosive diazonium salts. In the absence of metal, few aryltriphenylphosphonium salts have also been prepared from Ph3P and aryl halides but require very high temperature (>260 °C).[16−18] Jugé and co-workers[19] have reported a method based aryne chemistry for the preparation of P-stereogenic tetraarylphosphonium triflates at room temperature, but this method suffers from the use of expensive starting material and poor regioselectivity. Herein, we report a synthesis of aryltriphenylphosphonium bromides from Ph3P and aryl bromides (Scheme E) not only in the absence of metal but also at around 182 °C, a temperature comparable to that for the nickel-catalyzed method (Scheme C).

Scheme 1

Methods for the Synthesis of Aryltriphenylphosphonium Salts

Results and Discussion

As mentioned above, the reported metal-free synthesis of aryltriphenylphosphonium salts from Ph3P and aryl halides requires very high temperature (>260 °C),[16−18] we initially hypothesized that using Ph2PCy instead of Ph3P would lower the reaction temperature due to the stronger nucleophilicity of Ph2PCy than Ph3P.[20] To test this hypothesis, we chose 4-bromobiphenyl as a model compound for aryl halides. Screening solvents with a boiling point of around 200 °C revealed that tetraline (bp 207 °C) and PhCN (bp 191 °C) gave phosphonium salt 1 in yields less than 10% but phenol (bp 182 °C) afforded 1 in an excellent yield (92%) (Table , entries 1–3). Ethoxybenzene (bp 169 °C) gave 1 in 6% yield (entry 4). Replacing phenol with 2-chlorophenol (bp 175–176 °C) could also produce phosphonium salt 1 albeit in a lower yield (entry 5). This substantial decrease of reaction temperature by using phenol as a solvent encouraged us to test the reaction of Ph3P with 4-bromobiphenyl. Surprisingly, the corresponding phosphonium salt 2 was also obtained in an excellent yield (93%, entry 6), suggesting that higher nucleophilicity of Ph2PCy has no effect on the course of the reaction, whereas using PhCN as a solvent still led to a very low yield (5%, entry 7). For 4-iodobiphenyl, the corresponding phosphonium salt 3 was obtained in 51% yield (entry 8), whereas for 4-chlorobiphenyl, only a trace of the product was detected (entry 9).

Table 1

Exploration of Reaction Conditions for the Metal-Free Synthesis of Aryltriphenylphosphonium Saltsa

entry	solvent	reaction time (h)	R	X	product	yield (%)b
1	tetraline	40	Cy	Br	1	5
2	PhCN	40	Cy	Br	1	10
3	PhOH	5	Cy	Br	1	92
4	PhOEt	30	Cy	Br	1	6
5	2-ClC6H4OH	20	Cy	Br	1	44
6	PhOH	5	Ph	Br	2	93
7	PhCN	5	Ph	Br	2	5
8	PhOH	12	Ph	I	3	51
9	PhOH	23	Ph	Cl	4	trace

The optimal reaction conditions and the highest yield are indicated in bold.

Isolated yield of phosphonium salt.

The success in the synthesis of phosphonium salt 2 from Ph3P and 4-bromobiphenyl promoted us to examine a variety of aryl bromides. As shown in Table , polyaromatic aryl bromides such as 2-bromonaphthalene, 2-bromoanthracene, 9-bromophenanthrene, 4-bromo-1,1′:4′,1″-terphenyl, and 1-bromopyrene gave the corresponding phosphonium salts 5–9 in 69–90% yields. For heteroaromatic 5-bromo-1H-indole, phosphonium salt 10 was obtained in 82% yield. The hydroxymethyl group was tolerated as phosphonium salts 11 and 12 were obtained in 74 and 60% yields, respectively. 1,4-Dibromobenzene gave monophosphonium salt 13a (29%) with the concurrent formation of bisphosphonium salt 13b (7%). When 3 equiv of Ph3P was used, the yield of 13b was increased to 76% (13a: 8% yield). 1-Bromo-4-phenoxybenzene gave the corresponding phosphonium salt 14 in a nearly quantitative yield. For 2-bromo-6-methoxynaphthalene, however, we found that a demethylation product 15b formed in 14% yield besides the normal product 15a (72%). The demethylation is possibly through a mechanism similar to that for the K2CO3-catalyzed cleavage[21] of aryl alkyl ether by PhSH (with phenol and Ph3P to replace PhSH and K2CO3, respectively), but attempts to isolate anisole failed probably because of its low boiling point (bp 154 °C). The demethylation also happened for 1-bromo-3-methoxybenzene as phosphonium salt 17 formed in 34% yield with the concurrent formation of phosphonium salt 16 (27% yield), which could be separately obtained in 95% yield from 3-bromophenol. However, 4-bromophenol gave phosphonium salt 18 in a low yield (26%) though 2 equiv of 4-bromophenol was used. 3-Bromotoluene and 4-bromotoluene afforded phosphonium salts 19 and 20 in 63 and 82% yields, respectively, and the latter reaction was carried out using 2 equiv of Ph3P and at increasing concentration of reactants. 2-Bromobenzoic acid and 4-bromobenzoic acid gave zwitterionic phosphonium salts 21 and 22 in 75 and 58% yields, respectively, and the latter reaction required 2 equiv of 4-bromobenzoic acid and an increasing concentration of reactants. Phenyl 4-bromobenzoate gave phosphonium salts 23 in a 73% yield, whereas methyl 4-bromobenzoate led to a complicated mixture including phosphonium salt 21, a demethylation product, and phosphonium salt 23, an ester-exchanging product as indicated by thin layer chromatography (TLC). It is noteworthy that carboxylic acids and esters are not tolerated for the nickel- or palladium-catalyzed formation of phosphonium salts from Ph3P and aryl bromides.[12,13]

Table 2

Metal-Free Synthesis of Aryltriphenylphosphonium Bromidesa

Reaction conditions: Ph3P (1 mmol), ArBr (1 mmol), phenol (1.5 mL), and refluxed; the reaction was followed by TLC until Ph3P or ArBr was consumed.

When using 3 equiv of Ph3P, the yield of 13b increased to 76% (13a: 8%).

NMR yield.

Using 2 equiv of Ph3P and phenol (0.5 mL).

NMR yield. The NMR yield of demethylation product, 16, is 27%.

Using 2 equiv of ArBr and phenol (0.5 mL).

Although the precise reaction mechanism remains unclear, the nucleophilic addition ability of Ph3P to a variety of electron-deficient alkenes or alkynes[22,23] promotes us to propose a two-step addition–elimination mechanism, as shown in Scheme A, for the formation of phosphonium salts from Ph3P and aryl bromides. The first step is nucleophilic addition of Ph3P to aryl bromide 24 to form a zwitterionic intermediate 25, and the second step is the elimination of bromide to restore the aromaticity of the ring and furnish phosphonium salt 26. In both steps, phenol may form hydrogen bond with bromide to facilitate the addition of Ph3P and the elimination of bromide by further polarizing the carbon–bromide bond, rendering phenol the optimal solvent among the tested solvents (Table , entries 1–4 and 6–7). The reason that aryl bromide gives the best yield among the tested aryl halides (Table , entries 3 and 8–9) is possibly because triphenylphosphine as a soft nucleophile[24] prefers to attack the softer carbon bonding to bromide than that to chloride due to less charge on the carbon when softer Br– (than Cl–) is leaving in the transition state, whereas both aryl iodide and phosphonium iodide might be unstable in refluxing phenol. As the reaction is carried out in phenol, a weak acid, we wondered if the intermediate 25 could undergo proton exchange with phenol. Therefore, we performed a deuterium experiment using d4-1,4-dibromobenzene 27 as a substrate and expected that after the formation of zwitterionic intermediate 28, it could abstract a proton from phenol to produce phosphonium salt 29, which could lose a deuterium to generate the zwitterionic intermediate 30 and consequently produce phosphonium salt 13a-d after the elimination of bromide (Scheme B). However, after the isolation of the formed phosphonium salts, and the analysis by NMR (1H, 13C, and 31P) and high-resolution mass spectrometry (HRMS) indicated that only phosphonium salt 13a-d formed (some bisphosphonium salt 13b-d also formed), and no phosphonium salt 13a-d was detected. This result suggests that the second step in our proposed mechanism (Scheme A) is probably too fast to allow D–H exchange between the phenol and the intermediate 25. Another possibility is that the tripheylphosphonium cation and the carbon anion in the intermediate 25 might form a relatively intimate ion pair and the former blocks the latter to access phenol due to steric hindrance. As for the much lower yield of phosphonium salt 18 than that of phosphonium salt 16 (Table ), one possibility is that 18 could be deprotonated by Ph3P to form a ylide, 4-(triphenylphosphoranylidene)cyclohexa-2,5-dienone, which might undergo polymerization via Wittig olefination (Scheme C).

Scheme 2

Proposed Mechanism for the Formation of Aryldiphenylphosphonium Bromides

Aryltriphenylphosphonium salts can be readily hydrolyzed[25] to aryldiphenylphosphine oxide, which can be further reduced to aryldiphenylphosphine by a number of methods.[26−29] Therefore, the feasible and metal-free synthesis of aryltriphenylphosphonium salts from Ph3P and aryl bromides and its good tolerance of functional groups enable facile access to multifunctional aryldiphenylphosphines and their oxides. For example, treatment of phosphonium salt 12, which was obtained in 60% yield (Table ) from Ph3P and 4-bromo-3-(hydroxymethyl)phenol, with 3 M NaOH afforded phosphine oxide 31 in 57% yield, and the subsequent reduction[27] with methyldiethyoxysilane catalyzed by bis(4-nitrophenyl) phosphate gave phosphine 32 in 55% yield (Scheme ). Although the yield of each step is moderate, this two-step route to phosphine oxide 31 or three-step route to phosphine 32 is still attractive because it requires neither transition metal nor protection of two hydroxyl groups.

Scheme 3

Synthesis of Multifunctional Aryldiphenylphosphine and Its Oxide

In summary, we have developed a metal-free method for the synthesis of aryltriphenylphosphonium salts from Ph3P and aryl bromides. This method can be applied to aryl bromides bearing a variety of functional groups such as CH2OH, Ar-OH, and COOH. The reaction temperature is comparable to the reported method[12] using nickel as a catalyst. Further conversion of the resulting aryldiphenylphosphonium salt by hydrolysis and reduction also provides access to multifunctional aryldiphenylphosphines and their oxides without using transition metals and protection groups. Furthermore, a two-step addition–elimination mechanism is proposed, with the second step to eliminate a bromide being a fast step as indicated by the deuterium experiment.

Experimental Section

General

All chemicals were purchased from local companies and used as received. All reactions were performed under nitrogen by connecting the flask to a nitrogen balloon. The reflux was operated by using a heating mantle. 1H and 13C NMR spectra were recorded on a Bruker Avance 400 spectrometer. The IR spectra were recorded on a Thermo Nicolet Avatar 360 IR spectrometer. The HRMS spectra were recorded on a Varian 7.0 T FTMS.

Typical Procedure for the Synthesis of [1,1′-Biphenyl]-4-yl(cyclohexyl)diphenylphosphonium Bromide (1)

To a round-bottom flask (5 mL), 4-bromobiphenyl (233 mg, 1 mmol), Ph2PCy (268 mg, 1 mmol), and phenol (1.5 mL) were added. The resulting mixture was refluxed, and the reaction was followed by TLC. After completion (5 h), the reaction mixture was passed through a short silica gel (25 g) column eluted first with EtOAc to remove phenol and then with 1,2-dichloroethene (DCE)/MeOH (5:1, v/v). The latter fraction was evaporated under reduced pressure and then dried at 110 °C until no residue of solvent was detected by 1H NMR. By this procedure, phosphonium salt 1 was obtained as a pale yellow solid in 85% yield (426 mg). 1H NMR (400 MHz, dimethyl sulfoxide (DMSO)-d6) δ 0.97–1.15 (m, 3H), 1.52–1.87 (m, 5H), 2.00–2.13 (m, 2H), 4.32–4.45 (m, 1H), 7.45–7.60 (m, 3H), 7.75–7.85 (m, 6H), 7.87–8.03 (m, 8H), 8.05–8.11 (m, 2H); 13C NMR (101 MHz, DMSO-d6) δ 25.5, 25.6, 26.4, 29.1 (d, JC-P = 47.5 Hz), 116.3 (d, JC-P = 84.7 Hz), 117.9 (d, JC-P = 83.2 Hz), 127.7, 128.8 (d, JC-P = 12.6 Hz), 129.6, 129.8, 130.9 (d, JC-P = 12.1 Hz), 134.3 (d, JC-P = 9.5 Hz), 134.9 (d, JC-P = 9.8 Hz), 135.3 (d, JC-P = 2.5 Hz), 138.3, 146.4 (d, JC-P = 2.6 Hz); 31P NMR (162 MHz, DMSO-d6) δ 26.30. HRMS-ESI (positive) m/z: calcd for C30H30P+ [M – Br–] 421.2085, found 421.2079. Unless otherwise noted, other phosphonium salts were synthesized according to the same procedure as described above.

[1,1′-Biphenyl]-4-yltriphenylphosphonium Bromide (2)[13]

A white solid. Yield: 925 mg, 93%. 1H NMR (400 MHz, DMSO-d6) δ 7.48–7.53 (m, 1H), 7.57 (dd, J1 = 7.4 Hz, J2 = 7.4 Hz, 2H), 7.75–7.90 (m, 16H), 7.95–8.02 (m, 3H), 8.13 (dd, J1H-P = 2.8 Hz, J2 = 8.4 Hz, 2H); 13C NMR (101 MHz, DMSO-d6) δ 116.6 (d, JC-P = 91.1 Hz), 118.2 (d, JC-P = 89.3 Hz), 127.8, 129.0 (d, JC-P = 13.1 Hz), 129.7, 129.8, 131.0 (d, JC-P = 12.8 Hz), 135.0 (d, JC-P = 10.5 Hz), 135.7 (d, JC-P = 10.8 Hz), 135.9 (d, JC-P = 1.9 Hz), 138.2, 146.9 (d, JC-P = 2.4 Hz); 31P NMR (162 MHz, DMSO-d6) δ 22.13.

[1,1′-Biphenyl]-4-yltriphenylphosphonium Iodide (3)[13]

A yellow solid. Yield: 412 mg, 51%. 1H NMR (400 MHz, DMSO-d6) δ 7.47–7.61 (m, 3H), 7.75–7.90 (m, 16H), 7.97–8.03 (m, 3H), 8.14 (d, J = 7.6 Hz, 2H); 13C NMR (101 MHz, DMSO-d6) δ 116.6 (d, JC-P = 91.1 Hz), 118.3 (d, JC-P = 89.2 Hz), 127.8, 128.9 (d, JC-P = 12.2.1 Hz), 129.7, 129.8, 131.0 (d, JC-P = 12.8 Hz), 135.1 (d, JC-P = 10.5 Hz), 135.7 (d, JC-P = 11.0 Hz), 135.9 (d, JC-P = 2.6 Hz), 138.3, 147.0 (d, JC-P = 3.0 Hz); 31P NMR (162 MHz, DMSO-d6) δ 22.15.

Naphthalen-2-yltriphenylphosphonium Bromide (5)[30]

A gray solid. Yield: 404 mg, 86%. 1H NMR (400 MHz, DMSO-d6) δ 7.70–7.78 (m, 2H), 7.78–7.90 (m, 13H), 7.96–8.04 (m, 3H), 8.16 (d, J = 8.4 Hz, 1H), 8.19 (d, J = 8.0 Hz, 1H), 8.36 (d, J1H-P = 3.2 Hz, J2 = 8.4 Hz, 1H), 8.41 (d, JH-P = 15.3 Hz, 1H); 13C NMR (101 MHz, DMSO-d6) δ 115.2 (d, JC-P = 89.9 Hz), 118.4 (d, JC-P = 89.1 Hz), 127.8 (d, JC-P = 11.0 Hz), 128.6, 128.8, 130.0, 130.8 (d, JC-P = 12.6 Hz), 131.0, 131.0 (d, JC-P = 12.8 Hz), 132.6 (d, JC-P = 14.6 Hz), 135.1 (d, JC-P = 10.4 Hz), 135.7 (d, JC-P = 2.7 Hz), 135.9 (d, JC-P = 2.7 Hz), 138.4 (d, JC-P = 10.6 Hz); 31P NMR (162 MHz, DMSO-d6) δ 22.60.

Anthracen-2-yltriphenylphosphonium Bromide (6)

A yellow solid. Yield: 234 mg, 90%. 1H NMR (400 MHz, DMSO-d6) δ 7.62–7.75 (m, 3H), 7.80–7.92 (m, 12H), 7.95–8.07 (m, 3H), 8.19 (d, J = 8.3 Hz, 1H), 8.23 (d, J = 8.3 Hz, 1H), 8.45–8.57 (m, 2H), 8.85 (s, 1H), 8.90 (s, 1H); 13C NMR (101 MHz, DMSO-d6) δ 114.7 (d, JC-P = 90.3 Hz), 118.3 (d, JC-P = 89.2 Hz), 125.4 (d, JC-P = 11.0 Hz), 127.3, 127.4, 128.3, 128.7, 129.1, 129.8 (d, JC-P = 15.2 Hz), 130.1, 131.0 (d, JC-P = 12.8 Hz), 131.2 (d, JC-P = 12.5 Hz), 132.1 (d, JC-P = 2.4 Hz), 132.5, 134.0, 135.1 (d, JC-P = 10.4 Hz), 135.9 (d, JC-P = 2.8 Hz), 140.7 (d, JC-P = 10.2 Hz); 31P NMR (162 MHz, DMSO-d6) δ 22.61. HRMS-ESI (positive) m/z: calcd for C32H24P+ [M – Br–] 439.1616, found 439.1605.

Phenanthren-9-yltriphenylphosphonium Bromide (7)

A white solid. Yield: 466 mg, 90%. 1H NMR (400 MHz, DMSO-d6) δ 7.44–7.52 (m, 2H), 7.76–7.91 (m, 14H), 7.94–8.07 (m, 6H), 9.08 (d, J = 8.4 Hz, 1H), 9.14 (d, J = 8.5 Hz, 1H); 13C NMR (101 MHz, DMSO-d6) δ 113.2 (d, JC-P = 88.5 Hz), 118.6 (d, JC-P = 88.8 Hz), 123.9, 125.3, 127.7 (d, JC-P = 6.2 Hz), 128.3, 128.8, 129.0, 129.1 (d, JC-P = 8.5 Hz), 129.7 (d, JC-P = 15.4 Hz), 131.1 (d, JC-P = 13.0 Hz), 131.48 (d, JC-P = 10.6 Hz), 131.53, 132.3, 133.2 (d, JC-P = 2.3 Hz), 135.0 (d, JC-P = 10.5 Hz), 135.8 (d, JC-P = 2.8 Hz), 143.8 (d, JC-P = 10.5 Hz); 31P NMR (162 MHz, DMSO-d6) δ 22.20. HRMS-ESI (positive) m/z: calcd for C32H24P+ [M – Br–] 439.1616, found 439.1611.

[1,1′:4′,1″-Terphenyl]-4-yltriphenylphosphonium Bromide (8)

A white solid. Yield: 201 mg, 70%. 1H NMR (400 MHz, DMSO-d6) δ 7.40 (dd, J1 = 7.3 Hz, J2 = 7.3 Hz, 1H), 7.50 (dd, J1 = 7.6 Hz, J2 = 7.6 Hz, 2H), 7.72–7.90 (m, 18H), 7.94 (d, J = 8.0 Hz, 2H), 7.96–8.03 (m, 3H), 8.19 (dd, J1 = 2.8 Hz, J2 = 8.4 Hz, 2H); 13C NMR (101 MHz, DMSO-d6) δ 116.6 (d, JC-P = 91.1 Hz), 118.3 (d, JC-P = 89.4 Hz), 127.2, 128.0, 128.3, 128.4, 128.8 (d, JC-P = 13.2 Hz), 129.6, 131.0 (d, JC-P = 12.8 Hz), 135.1 (d, JC-P = 10.5 Hz), 135.7 (d, JC-P = 11.0 Hz), 135.9 (d, JC-P = 2.8 Hz), 137.0, 139.6, 141.3, 146.4 (d, JC-P = 2.8 Hz); 31P NMR (162 MHz, DMSO-d6) δ 22.15. HRMS-ESI (positive) m/z: calcd for C36H28P+ [M – Br–] 491.1929, found 491.1920.

Triphenyl(pyren-1-yl)phosphonium Bromide (9)

A yellow solid. Yield: 375 mg, 69%. 1H NMR (400 MHz, DMSO-d6) δ 7.66 (d, J = 9.3 Hz, 1H), 7.77–7.90 (m, 13H), 7.94–8.02 (m, 3H), 8.27 (d, J = 9.0 Hz, 1H), 8.31 (d, J = 7.7 Hz, 1H), 8.43 (d, J = 9.0 Hz, 1H), 8.50 (d, J = 7.6 Hz, 1H), 8.59–8.65 (m, 3H); 13C NMR (101 MHz, DMSO-d6) δ 108.7 (d, JC-P = 89.0 Hz), 119.1 (d, JC-P = 88.6 Hz), 123.3, 124.8 (d, JC-P = 7.7 Hz), 125.0 (d, JC-P = 10.5 Hz), 126.2, 127.7, 128.4, 128.7, 128.9, 129.8, 131.0, 131.13, 131.14 (d, JC-P = 12.8 Hz), 132.5, 134.1(d, JC-P = 8.5 Hz), 134.3 (d, JC-P = 11.6 Hz), 135.1 (d, JC-P = 10.4 Hz), 135.8 (d, JC-P = 2.9 Hz), 136.8 (d, JC-P = 2.3 Hz); 31P NMR (162 MHz, DMSO-d6) δ 22.08. HRMS-ESI (positive) m/z: calcd for C34H24P+ [M – Br–] 463.1616, found 463.1616.

(1H-Indol-5-yl)triphenylphosphonium Bromide (10)

A gray solid. Yield: 383 mg, 84%. 1H NMR (400 MHz, DMSO-d6) δ 6.68 (d, J = 2.9 Hz, 1H), 7.32–7.40 (m, 1H), 7.68 (d, J = 3.0 Hz, 1H), 7.70–7.85 (m, 12H), 7.85–7.92 (m, 2H), 7.92–7.99 (m, 3H), 12.08 (s, 1H); 13C NMR (101 MHz, DMSO-d6) δ 103.3, 105.2 (d, JC-P = 95.0 Hz), 114.4 (d, JC-P = 15.0 Hz), 119.6 (d, JC-P = 89.2 Hz), 125.8 (d, JC-P = 12.8 Hz), 128.8 (d, JC-P = 16.0 Hz), 129.1 (d, JC-P = 12.4 Hz), 129.3, 130.8 (d, JC-P = 12.6 Hz), 134.9 (d, JC-P = 10.3 Hz), 135.5 (d, JC-P = 2.8 Hz), 139.4 (d, JC-P = 2.6 Hz); 31P NMR (162 MHz, DMSO-d6) δ 23.60. HRMS-ESI (positive) m/z: calcd for C26H21NP+ [M – Br–] 378.1412, found 378.1403.

(4-(Hydroxymethyl)phenyl)triphenylphosphonium Bromide (11)[12]

A gray solid. Yield: 334 mg, 74%. 1H NMR (400 MHz, DMSO-d6) δ 4.67 (s, 2H), 5.64 (s, 1H), 7.66–7.78 (m, 10H), 7.79–7.87 (m, 6H), 7.94–8.01 (m, 3H); 13C NMR (101 MHz, DMSO-d6) δ 62.5, 115.7 (d, JC-P = 91.2 Hz), 118.4 (d, JC-P = 89.2 Hz), 128.3 (d, JC-P = 13.2 Hz), 131.0 (d, JC-P = 12.7 Hz), 134.97 (d, JC-P = 10.2 Hz), 135.00 (d, JC-P = 10.5 Hz), 135.8 (d, JC-P = 2.7 Hz), 151.4 (d, JC-P = 3.0 Hz); 31P NMR (162 MHz, DMSO-d6) δ 22.08.

(4-Hydroxy-2-(hydroxymethyl)phenyl)triphenylphosphonium Bromide (12)

After isolation by column chromatography, the obtained product was further purified by preparative TLC (DCE/acetone/water 50:60:1, v/v). A white solid. Yield: 280 mg, 60%. 1H NMR (400 MHz, DMSO-d6) δ 3.91 (s, 2H), 5.63 (brs, 1H), 6.90–7.03 (m, 2H), 7.39 (s, 1H), 7.67–7.83 (m, 12H), 7.88–7.95 (m, 3H), 11.26 (brs, 1H); 13C NMR (101 MHz, DMSO-d6) δ 62.3 (d, JC-P =4.3 Hz), 101.6 (d, JC-P = 96.4 Hz), 116.3 (d, JC-P = 14.4 Hz), 117.6 (d, JC-P = 11.1 Hz), 120.2 (d, JC-P = 89.9 Hz), 130.8 (d, JC-P = 12.9 Hz), 134.5 (d, JC-P = 10.3 Hz), 135.2 (d, JC-P = 2.0 Hz), 138.8 (d, JC-P = 14.0 Hz), 150.9 (d, JC-P = 9.9 Hz), 164.5; 31P NMR (162 MHz, DMSO-d6) δ 21.12. HRMS-ESI (positive) m/z: calcd for C25H22O2P+ [M – Br–] 385.1357, found 385.1351.

(4-Bromophenyl)triphenylphosphonium Bromide (13a)[12] and 1,4-Phenylenebis(triphenylphosphonium) Bromide (13b)[31]

After isolation by column chromatography, the mixture of 13a and 13b was further isolated by preparative TLC (DCE/MeOH 10:1, v/v) to yield 62 mg (29%) of 13a as a white solid and 22 mg (7%) of 13b as a white solid. When using 3 equiv of Ph3P, 13a and 13b were obtained in 8% (18 mg) and 76% (247 mg) yields, respectively. 13a: 1H NMR (400 MHz, DMSO-d6) δ 7.67 (dd, J1 = 8.5 Hz, J2H-P = 12.5 Hz, 2H), 7.72–7.87 (m, 12H), 7.94–8.02 (m, 3H), 8.05 (dd, J1H-P = 2.4 Hz, J2 = 8.5 Hz, 2H); 13C NMR (101 MHz, DMSO-d6) δ 117.7 (d, JC-P = 91.1 Hz), 117.8 (d, JC-P = 89.4 Hz), 130.7 (d, JC-P = 3.6 Hz), 131.0 (d, JC-P = 12.9 Hz), 134.1 (d, JC-P = 13.3 Hz), 135.1 (d, JC-P = 10.6 Hz), 136.0 (d, JC-P = 2.6 Hz), 136.8 (d, JC-P = 11.5 Hz); 31P NMR (162 MHz, DMSO-d6) δ 22.50. 13b: 1H NMR (400 MHz, DMSO-d6) δ 7.77–7.89 (m, 24H), 7.97–8.04 (m, 6H), 8.13 (dd, J1H-P = 5.8 Hz, J2H-P = 9.7 Hz, 4H); 13C NMR (101 MHz, DMSO-d6) δ 117.1 (d, JC-P = 89.5 Hz), 126.0 (dd, J1C-P = 3.5 Hz, J2C-P = 86.7 Hz), 131.1, 135.3, 136.2, 136.3 (dd, J1C-P = 10.2 Hz, J2C-P = 11.8 Hz); 31P NMR (162 MHz, DMSO-d6) δ 22.63.

(4-Phenoxyphenyl)triphenylphosphonium Bromide (14)

A white solid. Yield: 506 mg, 99%. 1H NMR (400 MHz, DMSO-d6) δ 7.23 (d, J = 8.0 Hz, 2H), 7.29–7.34 (m, 3H), 7.49–7.54 (m, 2H), 7.69–7.78 (m, 8H), 7.79–7.87 (m, 6H), 7.94–8.00 (m, 3H); 13C NMR (101 MHz, DMSO-d6) δ 110.3 (d, JC-P = 95.0 Hz), 118.6 (d, JC-P = 89.6 Hz), 119.1 (d, JC-P = 14.0 Hz), 121.0, 126.1, 131.0 (d, JC-P = 12.8 Hz), 131.1, 134.9 (d, JC-P = 10.5 Hz), 135.8 (d, JC-P = 2.8 Hz), 137.7 (d, JC-P = 12.0 Hz), 154.4, 163.5 (d, JC-P = 3.0 Hz); 31P NMR (162 MHz, DMSO-d6) δ 21.75. HRMS-ESI (positive) m/z: calcd for C30H24OP+ [M – Br–] 431.1565, found 431.1556.

(6-Methoxynaphthalen-2-yl)triphenylphosphonium Bromide (15a) and (6-Hydroxynaphthalen-2-yl)triphenylphosphonium Bromide (15b)

The isolation by column chromatography gave a mixture of 15a and 15b in a total yield of 430 mg (86%). NMR yields (based on the integration of peaks at 7.27 and 7.37): 15a, 14%; 15b, 72%. Both 15a and 15b could be partially isolated from their mixture by preparative TLC (eluted sequentially with DCE/MeOH/BuNH2 20:2:1 and DCE/MeOH 15:1, v/v) as a white solid. 15a: 1H NMR (400 MHz, DMSO-d6) δ 3.96 (s, 3H), 7.37 (dd, J1 = 2.5 Hz, J2 = 9.0 Hz, 1H), 7.60 (d, J = 2.2 Hz, 1H), 7.65 (ddd, J1 = 1.7 Hz, J2 = 8.7 Hz, J3H-P = 10.7 Hz, 1H), 7.75–7.86 (m, 12H), 7.95–8.02 (m, 3H), 8.07 (d, J = 9.1 Hz, 1H), 8.22 (dd, J1H-P = 3.3 Hz, J2 = 8.7 Hz, 1H), 8.31 (d, JH-P = 14.9 Hz, 1H); 13C NMR (101 MHz, DMSO-d6) δ 56.3, 106.8, 111.6 (d, JC-P = 92.5 Hz), 118.7 (d, JC-P = 89.3 Hz), 121.3, 128.2 (d, J = 14.7 Hz), 128.5 (d, JC-P = 11.1 Hz), 129.5 (d, J = 12.9 Hz), 131.0 (d, J = 12.8 Hz), 131.8, 135.1 (d, J = 10.5 Hz), 135.8 (d, J = 2.7 Hz), 137.8 (d, J = 11.0 Hz), 137.9 (d, JC-P = 1.9 Hz), 161.2; 31P NMR (162 MHz, DMSO-d6) δ 22.46; HRMS-ESI (positive) m/z: calcd for C29H24OP+ [M – Br–] 419.1565, found 419.1554. 15b: 1H NMR (400 MHz, DMSO-d6) δ 7.30 (d, J = 8.8 Hz, 1H), 7.35 (s, 1H), 7.51–7.58 (m, 1H), 7.74–7.86 (m, 12H), 7.94–8.02 (m, 4H), 8.08 (dd, J1H-P = 3.3 Hz, J2 = 8.8 Hz, 1H), 8.21 (d, JH-P = 15.0 Hz, 1H), 10.67–10.72 (m, 1H); 13C NMR (101 MHz, DMSO-d6) δ 109.4, 110.2 (d, JC-P = 92.5 Hz), 118.8 (d, JC-P = 89.3 Hz), 121.3, 127.3 (d, JC-P = 14.7 Hz), 128.1 (d, JC-P = 11.0 Hz), 128.8 (d, JC-P = 12.8 Hz), 130.9 (d, JC-P = 12.8 Hz), 132.1, 135.0, 135.7 (d, JC-P = 2.6 Hz), 137.99 (d, JC-P = 2.0 Hz), 138.04 (d, JC-P = 11.0 Hz), 159.9; 31P NMR (162 MHz, DMSO-d6) δ 22.41; HRMS-ESI (positive) m/z: calcd for C28H22OP+ [M – Br–] 405.1408, found 405.1406.

(3-Hydroxyphenyl)triphenylphosphonium Bromide (16)[2]

Reaction conditions: 3-bromophenol (173 mg, 1 mmol), Ph3P (524 mg, 2 mmol), and phenol (0.5 mL). A white solid. Yield: 414 mg, 95%. 1H NMR (400 MHz, DMSO-d6) δ 6.96–7.05 (m, 1H), 7.10–7.19 (m, 1H), 7.30–7.37 (m, 1H), 7.60–7.68 (m, 1H), 7.70–7.79 (m, 6H), 7.80–7.87 (m, 6H), 7.94–8.02 (m, 3H), 10.5 (s, 1H); 13C NMR (101 MHz, DMSO-d6) δ 118.2 (d, JC-P = 89.1 Hz), 119.0 (d, JC-P = 88.8 Hz), 120.9 (d, JC-P = 11.8 Hz), 122.9, 125.6, 130.9 (d, JC-P = 12.8 Hz), 132.4 (d, JC-P = 15.4 Hz), 135.0 (d, JC-P = 10.4 Hz), 135.8 (d, JC-P = 2.2 Hz), 159.0 (d, JC-P = 16.5 Hz); 31P NMR (162 MHz, DMSO-d6) δ 22.33.

(3-Methoxyphenyl)triphenylphosphonium Bromide (17)[13]

The isolation by column chromatography gave a mixture of 16 and 17 in a total yield of 269 mg (61%). NMR yields (based on the integration of peaks at 7.01 and 7.56): 16, 27%; 17, 34%. Phosphonium salt 17 could be partially isolated by preparative TCL (DCE/MeOH 30:1, v/v) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 3.80 (s, 3H), 7.15 (dd, J1 = 2.0 Hz, J2H-P = 14.4 Hz, 1H), 7.27 (dd, J1 = 8.4 Hz, J2H-P = 12.8 Hz, 1H), 7.55 (d, J = 8.4 Hz, 1H), 7.70–7.85 (m, 13H), 7.94–8.00 (m, 3H); 13C NMR (101 MHz, DMSO-d6) δ 56.3, 118.1 (d, JC-P = 89.1 Hz), 119.4 (d, JC-P = 89.0 Hz), 120.4 (d, JC-P = 11.8 Hz), 121.1, 127.1 (d, JC-P = 10.1 Hz), 130.9 (d, JC-P = 12.8 Hz), 132.6 (d, JC-P = 14.9 Hz), 135.1 (d, JC-P = 10.5 Hz), 135.9 (d, JC-P = 2.8 Hz), 160.4 (d, JC-P = 16.4 Hz); 31P NMR (162 MHz, DMSO-d6) δ 22.52.

(4-Hydroxyphenyl)triphenylphosphonium Bromide (18)[2]

Reaction conditions: 4-bromophenol (346 mg, 2 mmol), Ph3P (262 mg, 1 mmol), and phenol (0.5 mL). After isolation by column chromatography, the obtained product was further purified by preparative TLC (DCM/MeOH 30:1, v/v). A white solid. Yield: 111 mg, 26%. 1H NMR (400 MHz, DMSO-d6) δ 7.15–7.23 (m, 2H), 7.47–7.58 (m, 2H), 7.65–7.88 (m, 12H), 7.90–8.00 (m, 3H), 11.13 (brs, 1H); 13C NMR (101 MHz, DMSO-d6) δ 105.0 (d, JC-P = 98.1 Hz), 118.2 (d, JC-P = 14.1 Hz), 119.2 (d, JC-P = 89.6 Hz), 130.9 (d, JC-P = 12.6 Hz), 134.8 (d, JC-P = 10.5 Hz), 135.6 (d, JC-P = 2.8 Hz), 137.3 (d, JC-P = 12.2 Hz), 164.2 (d, JC-P = 2.9 Hz); 31P NMR (162 MHz, DMSO-d6) δ 21.65.

Triphenyl(m-tolyl)phosphonium Bromide (19)[12]

A white solid. Yield: 273 mg, 63%. 1H NMR (400 MHz, DMSO-d6) δ 2.42 (s, 3H), 7.52 (dd, J1 = 7.9 Hz, J2H-P = 13.0 Hz, 1H), 7.58 (d, JH-P = 13.4 Hz, 1H), 7.69–7.80 (m, 8H), 7.80–7.87 (m, 6H), 7.95–8.01 (m, 3H); 13C NMR (101 MHz, DMSO-d6) δ 21.5, 118.0 (d, JC-P = 88.7 Hz), 118.3 (d, JC-P = 89.1 Hz), 130.8 (d, JC-P = 13.1 Hz), 131.0 (d, JC-P = 12.7 Hz), 132.3 (d, JC-P = 10.4 Hz), 134.8 (d, JC-P = 10.4 Hz), 135.0 (d, JC-P = 10.5 Hz), 135.8 (d, JC-P = 2.7 Hz), 136.6 (d, JC-P = 2.8 Hz), 140.9 (d, JC-P = 12.9 Hz); 31P NMR (162 MHz, DMSO-d6) δ 22.23.

Triphenyl(p-tolyl)phosphonium Bromide (20)[12]

Reaction conditions: 1-bromo-4-methylbenzene (171 mg, 1 mmol), Ph3P (524 mg, 2 mmol), phenol (0.5 mL). A white solid. Yield: 355 mg, 82%. 1H NMR (400 MHz, DMSO-d6) δ 2.49 (s, 3H), 7.60–7.69 (m, 4H), 7.70–7.79 (m, 6H), 7.80–7.87 (m, 6H), 7.94–8.00 (m, 3H); 13C NMR (101 MHz, DMSO-d6) δ 21.8, 114.5 (d, JC-P = 91.7 Hz), 118.4 (d, JC-P = 89.4 Hz), 131.0 (d, JC-P = 12.9 Hz), 131.6 (d, JC-P = 13.3 Hz), 134.96 (d, JC-P = 10.4 Hz), 134.99 (d, JC-P = 11.0 Hz), 135.8 (d, JC-P = 2.8 Hz), 146.9 (d, JC-P = 3.0 Hz); 31P NMR (162 MHz, DMSO-d6) δ 22.10.

4-(Triphenylphosphonio)benzoate (21)[18]

Reaction conditions: 4-bromobenzoic acid (400 mg, 2 mmol), Ph3P (262 mg, 1 mmol), phenol (0.5 mL). After reaction, PhONa (174 mg, 1.5 mmol) and a mixture of ethanol and water (1:1, v/v, 50 mL) were added. The resulting mixture was refluxed for 1 h, evaporated under reduced pressure, and then isolated by column chromatography to give 21 as a yellow solid. Yield: 350 mg, 76%. IR (KBr, cm–1): 1694 (C=O). 1H NMR (400 MHz, DMSO-d6) δ 7.70–7.85 (m, 14H), 7.93–8.01 (m, 3H), 8.21 (d, J = 7.3 Hz, 2H), the proton peak of COOH did not appear; 13C NMR (101 MHz, DMSO-d6) δ 118.1 (d, JC-P = 89.1 Hz), 120.0 (d, JC-P = 88.7 Hz), 130.9 (d, JC-P = 11.8 Hz), 131.0 (d, JC-P = 12.8 Hz), 135.0 (d, JC-P = 8.1 Hz), 135.1 (d, JC-P = 10.5 Hz), 135.9 (d, JC-P = 2.5 Hz), 142.6, 167.2; 31P NMR (162 MHz, DMSO-d6) δ 22.33.

2-(Triphenylphosphonio)benzoate (22)

After the reaction, the work-up procedure is the same as that for phosphonium salt 21. A white solid. Yield: 270 mg, 58%. IR (KBr, cm–1): 1644 (C=O). 1H NMR (400 MHz, DMSO-d6) δ 6.94 (dd, J1 = 7.8 Hz, J2H-P = 13.7 Hz, 1H), 7.34–7.45 (m, 6H), 7.50–7.58 (m, 6H), 7.59–7.67 (m, 3H), 7.68–7.75 (m, 1H), 7.94–8.00 (m, 1H), 8.32 (dd, J1H-P = 3.5 Hz, J2 = 6.5 Hz, 1H), the proton peak of COOH did not appear; 13C NMR (101 MHz, DMSO-d6) δ 122.1 (d, JC-P = 113.0 Hz), 129.4 (d, JC-P = 12.9 Hz), 129.9 (d, JC-P = 10.9 Hz), 130.5, 132.09 (d, JC-P = 13.9 Hz), 132.11 (d, JC-P = 2.2 Hz), 132.5 (d, JC-P = 8.8 Hz), 135.8 (d, JC-P = 2.3 Hz), 137.1 (d, JC-P = 14.6 Hz), 143.6 (d, JC-P = 9.1 Hz), 165.3; 31P NMR (162 MHz, DMSO-d6) δ 5.46. HRMS-ESI (positive) m/z: calcd for C25H20O2P+ [M + H]+ 383.1201, found 383.1199.

(4-(Phenoxycarbonyl)phenyl)triphenylphosphonium Bromide (23)

A gray solid. Yield: 394 mg, 73%. IR (KBr, cm–1): 1737 (C=O). 1H NMR (400 MHz, DMSO-d6) δ 7.31–7.39 (m, 3H), 7.48–7.55 (m, 2H), 7.75–7.91 (m, 12H), 7.97–8.05 (m, 5H), 8.48 (dd, J1H-P = 2.9 Hz, J2 = 8.4 Hz, 2H); 13C NMR (101 MHz, DMSO-d6) δ 117.6 (d, JC-P = 89.3 Hz), 122.2, 124.1 (d, JC-P = 87.7 Hz), 126.9, 130.2, 131.1 (d, JC-P = 12.9 Hz), 131.6 (d, JC-P = 13.1 Hz), 135.19 (d, JC-P = 10.7 Hz), 135.20, 135.8 (d, JC-P = 10.9 Hz), 136.1 (d, JC-P = 2.7 Hz), 150.8, 163.9; 31P NMR (162 MHz, DMSO-d6) δ 22.46. HRMS-ESI (positive) m/z: calcd for C31H24O2P+ [M – Br–] 459.1514, found 459.1510.

(4-Bromo-phenyl-d4-)triphenylphosphonium Bromide (13a-d) and 1,4-Phenylene-d4-bis(triphenylphosphonium) Bromide (13b-d)

According to the same procedure as that for 13a and 13b, except that 1,4-dibromobenzene-d4 was used instead of 1,4-dibromobenzene, 13a-d and 13b-d were obtained as a white solid in 23% (50 mg) and 24% (78 mg) yields, respectively. 13a-d: 1H NMR (400 MHz, DMSO-d6) δ 7.75–7.92 (m, 12H), 8.00–8.07 (m, 3H); 13C NMR (101 MHz, DMSO-d6) δ 117.5 (d, JC-P = 90.9 Hz), 117.8 (d, JC-P = 89.5 Hz), 130.5 (d, JC-P = 3.8 Hz), 131.0 (d, JC-P = 13.0 Hz), 135.1 (d, JC-P = 10.7 Hz), 135.9 (d, JC-P = 2.8 Hz), the peaks of D–C did not appear due to the further splitting caused by deuterium; 31P NMR (162 MHz, DMSO-d6) δ 22.45; HRMS-ESI (positive) m/z: calcd for C24H15D4BrP+ [M – Br–] 421.0659, found 421.0658. 13b-d: 1H NMR (400 MHz, DMSO-d6) δ 7.75–7.89 (m, 24H), 7.97–8.04 (m, 6H); 13C NMR (101 MHz, DMSO-d6) δ 117.1 (d, JC-P = 89.5 Hz), 131.1, 135.3, 136.2, the peaks of D–C and P–C of 1,4-phenylene-d4 did not appear due to the further splitting caused by deuterium; 31P NMR (162 MHz, DMSO-d6) δ 22.57; HRMS-ESI (positive) m/z: calcd for C42H30D4P22+ [M – 2Br–] 302.1194, found 302.1197.

(4-Hydroxy-2-(hydroxymethyl)phenyl)diphenylphosphine Oxide (31)

Phosphine oxide 31 was obtained by hydrolysis of phosphonium salt 12 according to the literature procedure.[32] A white solid. Yield: 241 mg, 57%. 1H NMR (400 MHz, DMSO-d6) δ 4.47 (d, J = 5.4 Hz, 2H), 5.36 (t, J = 5.4 Hz, 1H), 6.64–6.68 (m, 1H), 6.78 (dd, J1 = 8.4 Hz, J2H-P = 13.5 Hz, 1H), 7.14–7.17 (m, 1H), 7.50–7.67 (m, 10H), 10.28 (s, 1H); 13C NMR (101 MHz, DMSO-d6) δ 55.4 (CH2Cl2 residue), 61.7 (d, JC-P = 4.6 Hz), 113.3 (d, JC-P = 13.8 Hz), 115.5 (d, JC-P = 11.0 Hz), 118.6 (d, JC-P = 108.1 Hz), 129.2 (d, JC-P = 11.7 Hz), 131.8 (d, JC-P = 9.6 Hz), 132.4 (d, JC-P = 2.2 Hz), 133.6 (d, JC-P = 102.6 Hz), 135.3 (d, JC-P = 13.7 Hz), 150.0 (d, JC-P = 9.2 Hz), 161.6 (d, JC-P = 2.7 Hz); 31P NMR (162 MHz, DMSO-d6) δ 29.44. HRMS-ESI (negative) m/z: calcd for C19H16O3P– [M – H+] 323.0837, found 323.0831.

4-(Diphenylphosphino)-3-(hydroxymethyl)phenol (32)

Phosphine 32 was prepared by the reduction of phosphophine oxide 31 according to the literature procedure.[27] A white solid. Yield: 109 mg, 55%. 1H NMR (400 MHz, DMSO-d6) δ 4.58 (dd, J1H-P = 1.6 Hz, J2 = 5.3 Hz, 2H), 5.22 (t, J = 5.3 Hz, 1H), 6.56–6.63 (m, 2H), 7.08–7.12 (m, 1H), 7.14–7.21 (m, 4H), 7.34–7.41 (m, 6H), 9.67 (s, 1H); 13C NMR (101 MHz, DMSO-d6) δ 61.4 (d, JC-P = 28.3 Hz), 113.9 (d, JC-P = 6.7 Hz), 114.4, 121.7 (d, JC-P = 11.0 Hz), 129.1 (d, JC-P = 6.6 Hz), 129.2, 133.6 (d, JC-P = 19.4 Hz), 134.7, 137.3 (d, JC-P = 10.9 Hz), 148.6 (d, JC-P = 23.8 Hz), 159.0; 31P NMR (162 MHz, DMSO-d6) δ −19.33. HRMS-ESI (negative) m/z: calcd for C19H16O2P– [M – H+] 307.0888, found 307.0891.