Nickel- and Palladium-Catalyzed Cross-Coupling of Aryl Fluorosulfonates and Phosphites: Synthesis of Aryl Phosphonates

Article abstract of DOI:10.1002/ejoc.202001485

The synthesis of aryl phosphonates via nickel and palladium-catalyzed cross-coupling of aryl fluorosulfonates and phosphites is described. The products were obtained in good to excellent yields under mild conditions with broad functional group compatibility, employing either Pd(OAc)₂ and DPEPhos or the readily available NiCl₂(dme) and Xantphos as catalytic systems. Noteworthily, the present C(sp²)?P bond formation method could be applied to the direct conversion of phenols to the corresponding aryl phosphonates in one pot via reaction of phenols with SO₂F₂ and subsequent palladium-catalyzed cross-coupling.

Full text of DOI:10.1002/ejoc.202001485

Communications
doi.org/10.1002/ejoc.202001485
1
2
3
4
5
6
7
8
9
Nickel- and Palladium-Catalyzed Cross-Coupling of Aryl
Fluorosulfonates and Phosphites: Synthesis of Aryl
Phosphonates
Guofu Zhang,[a] Jing Wang,[a] Chenfei Guan,[a] Yiyong Zhao,[b] and Chengrong Ding*[a]
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
be successfully deployed to accomplish direct metal insertion
into the typically inert CÀ O moiety. Furthermore, aryl fluorosul-
fonates have proved effective as precursors to form CÀ C, CÀ N,
CÀ H, and CÀ F bonds with high predictability via metal-catalyzed
CÀ O cleavage.[18,20] Such bond forming reactions involving
readily accessible aryl fluorosulfonates significantly expand the
portfolio of electrophiles available for cross-coupling under
synthetically attractive redox-neutral conditions.[21] As the
electrophilic partner, aryl fluorosulfonates have been used in
Negishi and Still cross-couplings[22] and palladium-catalyzed
alkoxy carbonylation reactions (Scheme 1a).[23] Researchers in
the group of Jiang and Hanley have independently reported
metal-catalyzed cross-couplings such as Suzuki and BuchwaldÀ
Hartwig amination couplings using aryl fluorosulfonates
(Scheme 1b).[24–26] Therefore, we envisioned that aryl fluorosulfo-
nates could be utilized in the formation of C(sp2)À P bonds.
Herein, we disclose the first palladium and nickel-catalyzed
cross-coupling of aryl fluorosulfonates with phosphites to
obtain aryl phosphonates in good to excellent yields. Using a
combination of Pd(OAc)2 and DPEPhos as a catalyst, the cross-
coupling provided excellent conversion of aryl fluorosulfonates
to aryl phosphonate products under mild conditions with broad
functional group compatibility. In addition, the first economical
nickel-catalyzed C(sp2)À P bond formation of aryl fluorosulfo-
nates using NiCl2(dme) in combination with Xantphos is
described, in which a variety of functionalized aryl fluorosulfo-
The synthesis of aryl phosphonates via nickel and palladium-
catalyzed cross-coupling of aryl fluorosulfonates and phosphites
is described. The products were obtained in good to excellent
yields under mild conditions with broad functional group
compatibility, employing either Pd(OAc)2 and DPEPhos or the
readily available NiCl2(dme) and Xantphos as catalytic systems.
Noteworthily, the present C(sp2)À P bond formation method
could be applied to the direct conversion of phenols to the
corresponding aryl phosphonates in one pot via reaction of
phenols with SO2F2 and subsequent palladium-catalyzed cross-
coupling.
Aryl phosphonates are among the most valuable compounds in
organic synthesis[1] due to their widespread use in numerous
practical applications such as pesticide synthesis, material
preparations, and as ligands and catalysts,[2,3] which has aroused
a growing interest in their synthesis in the past decades.[4] In
particular, the pioneering work by Hirao in 1981 prompted
great research interest in expanding the scope of the CÀ P
bond-forming process for the synthesis of aryl phosphonates.[5,6]
Among the numerous synthetic procedures, the metal-cata-
lyzed cross-coupling of various aryl halides,[7] aryl sulfonates,[8]
silanes,[9] diazonium salts,[10] pivalates[11] and organobismuth
compounds[12] with secondary phosphines and phosphine
oxides have been widely used. These methods have greatly
extended the scope of organic coupling partners to participate
in the formation of CÀ P bonds. However, the toxicity, cost, and
limited efficiency of these approaches hinder their practical
application in organic chemistry. [13,14]
Meanwhile, the cross-coupling of aryl fluorosulfonates has
recently emerged as a powerful tool for the construction of
organic molecules. As alternatives to halides or triflates, aryl
fluorosulfonates have great potential in transition metal-
catalyzed cross-coupling reactions due to their low cost, low
toxicity, and reliable preparation from phenol and sulfurylfluor-
ide (SO2F2), which is abundant and inexpensive.[15–17] As has
been amply demonstrated, the aryl fluorosulfonate bond can
[a] G. Zhang, J. Wang, C. Guan, Prof. Dr. C. Ding
College of Chemical Engineering, Zhejiang University of Technology
Hangzhou 310014, People’s Republic of China
E-mail: gfzhang@zjut.edu.cn
dingcr@zjut.edu.cn
[b] Y. Zhao
Zhejiang Ecological Environment Low Carbon Development Center
Hangzhou 310012, P. R. China
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/ejoc.202001485
Scheme 1. Transition metal-catalyzed cross-coupling reaction
Eur. J. Org. Chem. 2021, 810–813
810
© 2020 Wiley-VCH GmbH

Communications
doi.org/10.1002/ejoc.202001485
nates and diverse phosphites were tolerated. Finally, we
when the temperature was raised or lowered, and no reaction
occurred at room temperature.[27] Finally, the optimal conditions
for this C(sp2)À P bond cross-coupling reaction for the synthesis
of aryl phosphonates were set as follows: 5 mol% Pd(OAc)2,
1
2
3
4
5
6
7
8
9
developed a straightforward P-arylation of phenol by in situ
formation of the corresponding aryl fluorosulfonate followed by
efficient C(sp2)À P bond coupling for the synthesis of aryl
phosphonates in one pot. Overall, the present method is an
efficient and powerful approach for the synthesis of aryl
phosphonates from naturally abundant phenol.
°
6 mol% DPEPhos, and 2.0 equiv. of K2CO3 as a base at 80 C in
THF.
Next, considering the economic advantages of using nickel
as a catalyst, we investigated its ability to promote the C(sp2)À P
bond construction via the cleavage of the CÀ O bond of aryl
fluorosulfonates. Thus, we examined the cross-coupling of p-
biphenyl fluorosulfonate 1a with dibutyl phosphite 2a using a
series of nickel catalysts (Table 2), in particular, stable Ni(II)
sources such as NiCl2(PPh3)2, NiCl2(PCy3)2, NiCl2(dppe) and
NiCl2(dme) in combination with various phosphine ligands
including PPh3, BINAP, dppe, dppf, DPEPhos, PCy3·HBF4, and
Xantphos. After extensive attempts, we were pleased to find
that the use of NiCl2(dme) (5 mol%), Xantphos (6 mol%), Et3N
To test the feasibility of this C(sp2)À P cross-coupling
method, we conducted a preliminary study using p-biphenyl
fluorosulfonate 1a and dibutyl phosphite 2a as model sub-
strates. Initially, a series of phosphine ligands were explored
(Table 1). To our delight, using Pd(OAc)2/PPh3 as a catalyst and
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
°
Cs2CO3 as a base in THF at 80 C for 12 h led to the desired
product 3a in 20% yield (Table 1, entry 1). Encouraged by this
result, we further examined the effect of ligand, base, solvent,
and temperature on the reaction. We found that the type of
ligand was vital for this reaction. Thus, the product yield was
increased to 42% when using BINAP as a ligand (Table 1,
entry 2). Gratifyingly, DPEPhos proved to be the best ligand,
affording the desired product in 89% yield (Table 1, entries 4).
Then, using DPEPhos as the ligand of choice, a series of bases
were examined. Among the various bases screened, K2CO3
afforded the best result, producing 3a in 96% yield (Table 1,
entry 6). Meanwhile, a slight decrease in the yield of 3a was
observed using Na2CO3 as a base (Table 1, entry 5), and the use
of K3PO4 resulted in a lower yield of 67% (Table 1, entry 7). In
contrast, only a trace amount of the product was detected
when CsF was used as a base under the same conditions
(Table 1, entry 8). Other organic bases such as Et3N and DBU
gave the target product in 90% and 88% yield, respectively
(Table 1, entries 9 and 10). Replacing THF as a solvent with
DMF, toluene, DMSO, or 1, 4-dioxane decreased the yield
(Table 1, entries 11–14). The reaction temperature also affected
this cross-coupling. Thus, the yield of 3a decreased slightly
°
(2.0 eq.) and Zn (2.0 eq.) in DMF (2.0 mL) at 100 C for 12 h
provided the target product 3a in an excellent yield of 98%
(Table 2, entry 1). Unfortunately, using NiCl2(PPh3)2 instead of
NiCl2(dme) entirely suppressed the process (Table 2, entry 2),
and NiCl2(dppe) generated a moderate yield of the desired
product (Table 2, entry 3). The reaction conducted with
NiCl2(PCy3)2 as a catalyst occurred in a remarkably poor yield
under the same condition (Table 2, entry 4). Changing the
ligand to DPEPhos or PPh3 also decreased the yield (Table 2,
entries 5 and 6). These results imply that the choice of the
nickel source and the ligand played a pivotal role in the
reaction. Meanwhile, replacing the solvent or the base did not
improve the reaction efficiency (Table 2, entries 7 and 8). The
reaction also proceeded smoothly at lower and higher temper-
atures, although the yield decreased slightly (Table 2, entries 9
and 10). Finally, a control experiment indicated that the
reducing agent was essential for this cross-coupling since the
target product was not obtained in the absence of Zn (Table 2,
entry 11).[27]
Table 1. Optimization of conditions for the palladium-catalyzed cross-
coupling reaction.[a]
Table 2. Optimization of conditions for the nickel-catalyzed cross-coupling
reaction.[a]
Entry
L
Base
Solvent
THF
Yield [%][b]
Entry
Variation from standard conditions
Yield [%][b]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
PPh3
BINAP
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Na2CO3
K2CO3
K3PO4
CsF
Et3N
DBU
K2CO3
K2CO3
K2CO3
K2CO3
20
42
72
89
74
96
67
Trace
90
88
THF
THF
THF
THF
THF
THF
THF
THF
Xantphos
DPEPhos
DPEPhos
DPEPhos
DPEPhos
DPEPhos
DPEPhos
DPEPhos
DPEPhos
DPEPhos
DPEPhos
DPEPhos
1
2
3
4
5
6
7
8
9
none
98
52
0
4
74
NiCl2(PPh3)2 instead of NiCl2(dme)
NiCl2(dppe) instead of NiCl2(dme)
NiCl2(PCy)2 instead of NiCl2(dme)
DPEPhos instead of Xantphos
PPh3 instead of Xantphos
K2CO3 instead of Et3N
THF instead of DMF
Decreacing the temp. to 80 C
Increasing the temp. to 120 C
9
19
81
85
90
Trace
THF
DMF
Toluene
DMSO
1,4-dioxane
°
77
55
92
86
°
10
11
Without Zn
[a] Reaction conditions: 1a (0.2 mmol), 2a (0.3 mmol, 1.5 equiv.), NiCl2
(dme) (5 mol%), Xantphos (6 mol%), Et3N (0.4 mmol, 2.0 equiv.), Zn
[a] Reaction conditions: 1a (0.2 mmol), 2a (0.3 mmol, 1.5 equiv.), Pd(OAc)2
(5 mol%), ligand (6 mol%), base (0.4 mmol, 2.0 equiv.) and solvent (2.0 mL)
°
(0.3 mmol, 1.5 equiv.) and DMF (2.0 mL) at 100 C for 12 h. [b] Isolated
yield.
°
at 80 C for 12 h. [b] Isolated yield.
Eur. J. Org. Chem. 2021, 810–813
www.eurjoc.org
811
© 2020 Wiley-VCH GmbH

Communications
doi.org/10.1002/ejoc.202001485
With these optimized reaction conditions in hand, the
1
2
3
4
5
6
7
8
9
substrate scope of aryl fluorosulfonates for the construction of
C(sp2)À P bonds was investigated. Gratifyingly, the scope of the
reaction was very broad and accommodated a variety of
functions in the aryl fluorosulfonates and the phosphites. As
summarized in Scheme 2, the reaction conditions were compat-
ible with electronically and sterically diverse aryl fluorosulfo-
nates, bearing a wide range of functional groups and synthetic
handles including biaryls, ethers, esters, nitriles, ketones, aryl,
halides, naphthalenes, and heterocycles. It is worth mentioning
that aryl fluorosulfonates containing electron-withdrawing func-
tional groups were converted to the corresponding aryl
phosphonates in higher yields than aryl fluorosulfonates
containing electron-donating groups under these reaction
conditions. Generally, palladium and nickel catalysis afforded
comparable yields in the majority of the examples examined.
However, the transformation of 4-CN aryl fluorosulfonates was
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
Scheme 3. Substrate scope. Reaction conditions: (1) phenol derivative
(0.2 mmol); Et3N (1.2 equiv.), SO2F2 gas (balloon), THF (2 mL), (2) phosphite
(0.3 mmol, 1.5 equiv.), Pd(OAc)2 (5 mol%), DPEPhos (6 mol%), K2CO3
(0.4 mmol, 2.0 equiv.).
much more effective using the Ni-catalyst system, whereas the
latter showed relatively low reactivities towards halide-substi-
tuted fluorosulfonates compared with the Pd-catalyst system.
Furthermore, H-phosphites with different alkyl and alkoxy
groups could also participate in the reaction with aryl
fluorosulfonates smoothly, affording the corresponding cross-
coupling products in excellent yields. In general, the inexpen-
sive nickel catalyst provided a complementary scope to the Pd-
catalyzed C(sp2)À P bond formation.
Finally, we envisioned that the present method could be
used for the direct conversion of phenols to the corresponding
aryl phosphonates in one pot. A balloon full of SO2F2 gas was
used to quantitatively convert phenols into 1a in the presence
of THF and 1.2 equiv. of Et3N after 6 h at room temperature. The
remaining SO2F2 was easily removed from the system before
the subsequent cross-coupling reaction by simply sparging with
nitrogen. Surprisingly, using the palladium catalyst in this one-
pot synthesis afforded the corresponding aryl phosphonates in
good yields from a variety of substituted phenol and phos-
phites (Scheme 3).
In summary, we report the successful C(sp2)À P cross-
coupling between aryl fluorosulfonates and phosphites cata-
lyzed by a combination of palladium and DPEPhos or nickel and
Xantphos. The reaction proceeded efficiently to produce a
broad range of aryl phosphonates under mild conditions.
Conflict of Interest
The authors declare no conflict of interest.
Keywords: Cleavage reactions
Palladium · Phosphorylation
· Cross-coupling · Nickel ·
Scheme 2. Substrate scope. Reaction conditions: [Pd]: 1 (0.2 mmol), 2
(0.3 mmol, 1.5 equiv.), Pd(OAc)2 (5 mol%), DPEPhos (6 mol%), K2CO3
°
(0.4 mmol, 2.0 equiv.) in THF (2.0 mL) at 80 C for 12 h; [Ni]: 1 (0.2 mmol), 2
(0.3 mmol, 1.5 equiv.), NiCl2(dme) (5 mol%), Xantphos (6 mol%), Et3N
[1] a) A. Skarżyńska, Coord. Chem. Rev. 2013, 257, 1039–1048; b) Q. Xu, Y. B.
Zhou, C. Q. Zhao, S. F. Yin, L. B. Han, Mini-Rev. Med. Chem. 2013, 13,
824–835.
°
(0.4 mmol, 2.0 equiv.), Zn (0.3 mmol, 1.5 equiv.) and DMF (2.0 mL) at 100 C
for 12 h. [b] Isolated yield. See the SI for full details.
Eur. J. Org. Chem. 2021, 810–813
www.eurjoc.org
812
© 2020 Wiley-VCH GmbH

Communications
doi.org/10.1002/ejoc.202001485
[2] Q. Clemence, P. Marc, J. Pascal, Knight, D. Andrew, B. Bruno, Chem. Rev.
2012, 112, 3777–3807.
[3] D. S. Charles, K. L. Niels, Bunch, Lennart, Chem. Rev. 2011, 111, 7981–
Chem. Int. Ed. 2014, 53, 9466–9470; Angew. Chem. 2014, 126, 9620–
9624; c) Q. B. Liang, P. Xing, Z. G. Huang, J. J. Dong, K. B. Sharpless, X. X.
Li, B. Jiang, Org. Lett. 2015, 17, 1942–1945; d) S. D. Schimler, M. A.
Cismesia, P. S. Hanley, R. D. J. Froese, M. J. Jansma, D. C. Bland, M. S.
Sanford, J. Am. Chem. Soc. 2017, 139, 1452–1455.
1
2
3
4
5
6
7
8
8006.
[4] C. Y. Leung, J. Park, J. W. De Schutter, M. Sebag, A. M. Berghuis, Y. S.
Tsantrizos, J. Med. Chem. 2013, 56, 7939–7950.
[5] T. Hirao, T. Masunaga, Y. Ohshiro, T. Agawa, Synthesis 1981, 1, 56–57.
[6] A. Kunfermann, C. Lienau, B. Illarionov, J. Held, T. Grawert, C. T.
Behrendt, P. Werner, S. Hahn, W. Eisenreich, U. Riederer, B. Mordmüller,
A. Bacher, M. Fischer, M. Groll, T. Kurz, Eur. J. Med. Chem. 2013, 56,
8151–8162.
[18] C. Zhao, W. Y. Fang, K. P. Rakesh, H. L. Qin, Org. Chem. Front. 2018, 5,
179–183.
[19] S. D. Schimler, M. A. Cismesia, P. S. Hanley, R. D. J. Froese, M. J. Jansma,
D. C. Bland, M. S. Sanford, J. Am. Chem. Soc. 2017, 139, 1452–1455.
[20] X. Y. Wang, J. Leng, S. M. Wang, A. M. Asiri, H. M. Marwani, H. L. Qin,
Tetrahedron Lett. 2017, 58, 2340–2343.
[7] a) J. L. Montchamp, Y. R. Dumond, J. Am. Chem. Soc. 2001, 123, 510–511;
b) M. Kalek, A. Ziadi, J. Stawinski, Org. Lett. 2008, 10, 4637–4640; c) A. J.
Bloomfield, S. B. Herzon, Org. Lett. 2012, 14, 4370–4373; d) E. L. Deal, C.
Petit, J. L. Montchamp, Org. Lett. 2011, 13, 3270–3273; e) O. Berger, C.
Petit, E. Deal, J. L. Montchamp, Adv. Synth. Catal. 2013, 355, 1361–1373.
[8] K. S. Petrakis, T. L. Nagabhushan, J. Am. Chem. Soc. 1987, 109, 2831–
2833.
[21] a) J. J. Dong, L. Krasnova, M. G. Finn, K. B. Sharpless, Angew. Chem. Int.
Ed. 2014, 53, 9430–9448; Angew. Chem. 2014, 126, 9584–9603; b) J. J.
Dong, K. B. Sharpless, Kwisnek, L. Oakdale, J. S. Fokin, V. V. Fokin,
Angew. Chem. Int. Ed. 2014, 53, 9466–9670; Angew. Chem. 2014, 126,
9620–9624.
[22] G. P. Roth, C. E. Fuller, J. Org. Chem. 1991, 56, 3493–3496.
[23] a) C. Ma, C. Q. Zhao, X. T. Xu, Z. M. Li, X. Y. Wang, K. Zhang, T. S. Mei,
Org. Lett. 2019, 21, 2464–2467; b) W. Y. Fang, J. Leng, H. Li Qin, Asian J.
Org. Chem. 2017, 12, 2323–2327.
[24] Q. B. Liang, P. Xing, Z. G. Huang, J. J. Dong, K. B. Sharpless, X. X. Li, B.
Jiang, Org. Lett. 2015, 17, 1942–1945.
[25] P. S. Hanley, M. S. Ober, A. L. Krasovskiy, G. T. Whiteker, W. J. Kruper, ACS
Catal. 2015, 5, 5041–5046.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
[9] H. Q. Luo, H. D. Liu, X. W. Chen, K. K. Wang, X. Z. Luo, K. J. Wang, Chem.
Commun. 2017, 53, 956–958.
[10] R. Berrino, S. Cacchi, G. Fabrizi, A. Goggiamania, P. Stabile, Org. Biomol.
Chem., 2010, 8, 4518–4520.
[11] J. Yang, T. Q. Chen, L. B. Han, J. Am. Chem. Soc. 2015, 137, 1782–1785.
[12] T. Wang, S. Sang, L. Liu, H. W. Qiao, Y. X. Gao, Y. F. Zhao, J. Org. Chem.
2014, 79, 608–617.
[13] J. Zakzeski, P. C. A. Bruijnincx, A. L. Jongerius, B. M. Weckhuysen, Chem.
Rev. 2010, 110, 3552–3599.
[14] B. M. Rosen, K. W. Quasdorf, D. A. Wilson, N. Zhang, A. M. Resmerita,
N. K. Garg, V. Percec, Chem. Rev. 2011, 111, 1346–1416.
[15] E. E. Kenaga, J. Econ. Entomol. 1957, 50, 1–6.
[16] A. Cao, M. X. Guo, D. D. Yan, L. G. Mao, Q. X. Wang, Y. Li, X. Y. Duana,
P. S. Wang, Pest Manage. Sci. 2014, 70, 219–227.
[17] a) J. J. Dong, L. Krasnova, M. G. Finn, K. B. Sharpless, Angew. Chem. 2014,
126, 9584–9603; Angew. Chem. Int. Ed. 2014, 53, 9430–9448; b) J. J.
Dong, K. B. Sharpless, L. Kwisnek, J. S. Oakdale, V. V. Fokin, Angew.
[26] P. S. Hanley, T. P. Clark, A. L. Krasovskiy, M. S. Ober, J. P. O’Brien, T. S.
Staton, ACS Catal. 2016, 6, 3515–3519.
[27] Full details of the initial reaction are available in the supporting
information.
Manuscript received: November 12, 2020
Revised manuscript received: December 29, 2020
Accepted manuscript online: December 30, 2020
Eur. J. Org. Chem. 2021, 810–813
www.eurjoc.org
813
© 2020 Wiley-VCH GmbH