Pd-Catalyzed P-Arylation of Triarylantimony Dicarboxylates with Dialkyl H-Phosphites without a Base: Synthesis of Arylphosphonates

Abstract

The reaction of triarylantimony diacetates [Ar₃Sb(OAc)₂] with dialkyl H-phosphites [H-PO(OR)₂] in the presence of a Pd(PPh₃)₄ (5 mol%) catalyst led to the formation of arylphosphonates in moderate to excellent yield under base-free conditions. This reaction is the first example of carbon–phosphorus bond formation by using an organoantimony compound as a pseudo-halide.

Phosphorus–carbon (P–C) bond formation for the synthesis of organophosphorus compounds is a fundamental and significant research topic in organic synthesis, materials, and biology.^1–6) Among these, the transition-metal-catalyzed cross-coupling reaction is one of the most practical methods in modern organic syntheses.^7–9) With regard to the synthesis of arylphosphonates, the Pd-catalyzed cross-coupling reactions of aryl halides with dialkyl H-phosphites (i.e., Hirao P-arylation) have proved to be a powerful method.^10–21) The general procedure of these P-arylations involves a Pd-phosphine complex as the catalyst with the use of a stoichiometric or an excess amount of a base. Recently, different aryl substances were investigated for their reactivity with phosphorus agents. Sulfonates,^22,23) diaryliodonium salts,²⁴⁾ arylboronic acids,²⁵⁾ aryldiazonium salts,²⁶⁾ and triarylbismuthanes²⁷⁾ have been reported to be useful for P–C bond formation as the arylating reagents with dialkyl H-phosphites; however, a base and/or an additive was required for the transformation.

On the other hand, Pd-catalyzed cross-coupling reactions using organoantimony compounds have recently been the focus of attention. Triarylantimony dicarboxylates act as effective arylating agents in Pd-catalyzed C–C(Ar) bond formation reactions such as Heck-,^28–30) Stille-,³¹⁾ and Hiyama-type³²⁾ reactions. Over the past few years, we have also found that they are an efficient aryl donors in base-free Suzuki-type reactions and copper- and base-free Sonogashira-type reactions.^33–35) Moreover, base-free Miyaura-type cross-coupling reactions for boron–carbon (B–C) bond formation using triarylantimony diacetates and tetra(alkoxo)diborons afforded the corresponding arylboronates.³⁶⁾ As a continuation of our studies on heteroatom–carbon bond formation, we now report a novel Pd-catalyzed Hirao-type P-arylation of a pentavalent organoantimony compound, triarylantimony diacetate, with dialkyl H-phosphites afford to the corresponding arylphosphonates without using any base.

Results and Discussion

We initially focused our attention on the determination of the optimum conditions for the P-arylation of organoantimony(V) and bismuth(V) compounds (1a–8) with diethyl phosphite (9a) without using a base. The results including the search for active substrates, optimum amount of phosphorus reagent and suitable catalysts for the reaction are summarized in Table 1. The progress of the reaction was monitored by gas–liquid chromatography (GLC) and the reaction time was determined when the yields of products 10, 11, and Ph₃M (12, 13) showed a maximum value because it is impossible to detect the disappearance of the starting material and phosphorus reagent by thin-layer chromatography or GLC. First, we performed the reactions of 9a (1.2 eq) with a variety of antimony reagents (1a–6) to compare the reactivity using 5 mol% of Pd(PPh₃)₄ as catalyst in 1,4-dioxane at 60°C under argon atmosphere (entries 1–8). In comparison with these results, triphenylantimony dicarboxylates (1a, 2) and pentavalent bismuth(V) compounds (7, 8) afforded the expected diethyl phenylphosphonate (10) in good to high yields along with homo-coupling product (11) and reductive products (12, 13). Among these, triphenylantimony diacetate (1a) appeared to be the best substrate for this reaction in terms of the yield (77%) of the cross-coupling product (10) and reaction time (6 h). Next, optimum amount of phosphorus reagent was determined by the reaction of 1a with 9a because 1a had three phenyl groups (entries 1, 9–11). The reaction of 1a with 9a in the ratio 1 : 0.9 was proved to be the best, affording the cross-coupling product (10) in the highest yield (94%) and with extremely small amounts the by-products (entry 11). The reaction of 1a with an excess amount diethyl phosphite (9a) afforded the reductive by-product (12) in 10–45% yields (entries 1, 9, 10). Thus, this reaction is sensitive to the amount of dialkyl H-phosphite. These results show that one of the three phenyl groups on antimony is involved in the present carbon-phosphours bond formation. We also examined a similar reaction using other catalytic systems such as Pd(dba)₂, Pd(dba)₂-dppf, PdCl₂, Pd(OAc)₂, and PdCl₂(PPh₃)₂. They were inferior to Pd(PPh₃)₄ in the terms of the reaction time and yield of the cross-coupling product (entries 12–16). The screening of solvent showed that the reaction proceeded effectively in dioxane (94%), 1,2-dichloroethane (DCE) (78%), 1,2-dimethoxyethane (DME) (75%) and tetrahydrofuran (THF) (71%) whereas toluene, CH₃CN, N-methylpyrrolidone (NMP) and EtOH gave inferior results (entries 17–23). The addition of a base such as triethylamine to facilitate the Hirao reaction decreased the yield of the coupling product (10) (38%). We have previously reported that the B-arylation of triarylantimony diacetates with diboron reagents in the presence of PdCl₂(PPh₃)₂ under an aerobic conditions, affording arylboronates in which two of the three aryl groups on the antimony participated in the formation of coupling products.³⁶⁾ Unfortunately, the yield of 10 in this P-arylation decreased to 30% in an aerobic conditions. Consequently, the best result was obtained when 1a was treated with 9a (0.9 eq) by using Pd(PPh₃)₄ (5 mol%) in 1,4-dioxane at 60°C under an argon atmosphere (entry 11).

Table 1. Pd-Catalyzed P-Arylation of Organoantimony and Bismuth Reagents (1a–8) with Diethyl Phosphite (9a)^a)

Entry		M	X	Ratiob)	Pd catalyst	Solvent	Time (h)	10 (%)	11 (%)	12 or 13 (%)
1c)	1a	Sb	OAc	1 : 1.2	Pd(PPh3)4	Dioxane	6	77	3	10
2c)	2		OBz				6	58	3	8
3c)	3		OTs				24	46	<1	10
4c)	4		Cl				24	<1	14	1
5c)	5		Br				24	<1	11	9
6c)	6		Ph				24	36	4	37
7c)	7	Bi	OAc				24	66	20	3
8c)	8		Cl				24	57	2	2
9c)	1a	Sb	OAc	1 : 3			6	19	<1	45
10c)	1a			1 : 2			6	37	4	24
11d)	1a			1 : 0.9			6	94 (89)e)	2	3
12d)	1a				Pd(dba)2		24	24	6	15
13d)	1a				Pd(dba)2+dppf		24	70	3	5
14d)	1a				PdCl2		24	<1	<1	38
15d)	1a				Pd(OAc)2		24	<1	<1	25
16d)	1a				PdCl2(PPh3)2		24	<1	<1	14
17d)	1a				Pd(PPh3)4	1,2-DCE	24	78	15	6
18d)	1a					DME	6	75	13	7
19d)	1a					THF	3	71	17	5
20d)	1a					Toluene	24	22	5	7
21d)	1a					NMP	24	18	35	8
22d)	1a					CH3CN	24	<1	<1	2
23d)	1a					EtOH	24	<1	<1	<1

a) 1a–8 (0.5 mmol), Pd(PPh₃)₄ (0.025 mmol), b) 1a–8 : 9a, c) GC yield using octadecane as internal standard. The yield 100% corresponds to the formation of 0.5 mmol of 10, 0.75 mmol of 11 and 0.5 mmol of Ph₃M (12, 13), d) the yield 100% corresponds to the formation of 0.45 mmol of 10 and 12, 0.675 mmol of 11, e) isolated yield is shown in parenthesis.

To study the substrate scope and limitation of this P-arylation, we carried out the coupling reaction of triarylantimony diacetates (1) with dialkyl H-phosphites (9) using the optimized reaction conditions (Table 1, entry 11). The reaction time was fixed at 6 h because the endpoint of reaction was not clear. The results are summarized in Table 2. The reaction of dialkyl H-phosphites (9b–d) affored the corresponding arylphosphonates (14–16) in high yields (entries 1–3). We also examined a similar reaction using other phosphorus compounds, such as HPPh₂, HPCy₂ and P(OEt)₃. However, all these compounds gave the cross-coupling products in miserably poor yields (<4% yields), and provided the homo-coupling and reduction products of 1a.

Table 2. Pd-Catalyzed Hirao-Type Coupling Reaction of Triarylantimony Diacetates (1) with Dialkyl H-Phosphites (9)^a)

Entry		Ar		R		Yield (%)b)
1	1a	Phenyl	9b	i-Pr	14	98
2	1a		9c	n-Bu	15	93
3	1a		9d	Me	16	90
4	1b	4-Methoxyphenyl	9a	Et	17	95
5	1c	4-Methylphenyl	9a		18	93
6	1d	2-Methylphenyl	9a		19	45
7	1e	4-Bromophenyl	9a		20	76
8	1f	4-Trifluoromethylphenyl	9a		21	97
9	1g	Mesityl	9a		22	3

a) 1 (0.5 mmol), 9 (0.45 mmol), Pd(PPh₃)₄ (0.025 mmol). b) Isolated yield.

The reactions of various triarylantimony diacetates (1b–f), bearing electron-donating and -withdrawing groups on the phenyl ring, with 9a under the same reaction conditions afforded the corresponding products in excellent to good yields except 1d (entries 4–8). The reaction could be applied to a highly reactive substrate, tris(4-bromophenyl)antimony diacetate (1e), whose carbon–bromine bond remained intact and other by-products were not observed (entry 7). In the methyl-substituted antimony agents (1c, d, g), the influence of the steric hindrance of antimony reagents 1 was remarkable (entries 5, 6, 9). The most bulky mesityl derivative [(Mes)₃Sb(OAc)₂] was practically inactive (entry 9).

A plausible reaction mechanism of this P-arylation is shown in Chart 1. The catalytic cycle of this reaction would be similar to that of the Heck-type C-arylation of alkenes reported by Moiseev et al. and the Pd-catalyzed base-free B-arylation of Ar₃Sb(OAc)₂ with tetra(alkoxo)diboron reported by us.^29,36) The initial step of the reaction would be oxidative addition of the Ar–Sb bond of 1 onto the Pd(0) species (A) to form ArPdSb complex (B). The complex (B) thus formed is transformed to ArPdOAc complex (C) accompanied by elimination of Ar₂SbOAc. The Pd-catalyzed P-arylation of aryl halides with dialkyl H-phosphites is promoted by acetate ions, and ArPdOAc (C) is the key intermediate for reaction mechanism.^12,13,19) The ligand exchange of ArPdOAc (C) with dialkyl H-phosphite (9) gives ArPdP(O)(OR)₂ intermediate D, which undergo reductive elimination to form the coupling product and regenerate the Pd(0) species (A).

Chart 1. Possible Mechanism

In conclusion, we developed triarylantimony diacetates as a new P-arylating agent that can be used under mild reaction conditions without a base. This antimony reagent acts as a pseudo-halide and is effective for Pd catalyzed carbon-heteroatom (phosphorus) bond formation as well as previous described carbon–carbon and carbon–boron bond formation such as Suzuki-, Sonogashira- and Miyaura-type cross-coupling reactions. Further applications of these triarylantimony diacetates and similar pentavalent organoantimony compounds to other types of cross-coupling reactions are under way in our group.

Experimental

General Remarks

Melting points were taken on a Yanagimoto micro melting point hot-stage apparatus (MP-S3) and are not corrected. ¹H-NMR (tetramethylsilane (TMS): δ: 0.00 as an internal standard) and ¹³C-NMR (CDCl₃: δ: 77.00 as an internal standard) spectra were recorded on a JEOL JNM-ECA400 (400 MHz and 100 MHz) spectrometers in CDCl₃ unless otherwise stated. Mass spectra (MS) were obtained on a JEOL JMP-DX300 instrument (70 eV, 300 µA). All chromatographic separations were accomplished with Silica Gel 60N (Kanto Chemical Co., Inc., Japan). Thin-layer chromatography (TLC) was performed with Macherey-Nagel Pre-coated TLC plates Sil G25 UV₂₅₄.

Materials

Dialkyl H-phosphites (9a–d) were purchased from Wako Pure Chemical Industries, Ltd. and TCI Fine Chemicals, Japan. Triphenylantimony diacetate (1a) was purchased from TCI Fine Chemicals, Japan, and other triarylantimony diacetates such as 1b–d,²⁹⁾ 1e,³⁶⁾ 1f,³⁴⁾ 1g²⁹⁾ were prepared according to the reported procedures.

Typical Procedure for P-Arylation of Triarylantimony Dicarboxylates with Dialkyl H-Phosphites

A solution of triaryantimony diacetate (1) (0.5 mmol), dialkyl H-phosphite (9) (0.45 mmol), and tetrakis(triphenylphosphine)palladium (5 mol%, 0.025 mmol) in dioxane (5 mL) was heated at 60°C for 6 h under an argon atmosphere. After dilution with ether (30 mL) and saturated aqueous NH₄Cl (20 mL), the reaction mixture was separated and the aqueous layer was extracted with ether (30 mL×2). The combined organic layer was washed with brine, dried over anhydrous MgSO₄ and concentrated under reduced pressure. The crude residue was purified by column chromatograph (hexane–ethyl acetate) on silica gel to give arylphosphonates (10, 14–22). The products [10,³⁷⁾ 14,³⁷⁾ 15,²⁴⁾ 16–19,³⁷⁾ 20,¹⁹⁾ 21,³⁷⁾ 22³⁸⁾] were colorless oil, and were confirmed by comparison of NMR data and MS spectra with that in the literature.

Acknowledgments

This work was supported by a Grant-in-Aid for Scientific Research (C) from the Ministry Education, Culture, Sports, Sciences and Technology of Japan. Financial was support by Institute of Pharmaceutical Life Sciences, Aichi Gakuin University and the Special Research Found from Hokuriku University.

Conflict of Interest

The authors declare no conflict of interest.

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