Mendeleev Commun., 2018, 28, 323–325
Table 2 Screening of catalytic systems for homocoupling of 4bromo
toluene 1b.
In conclusion, a simple and efficient onepot twostep SSHC
under solventfree conditions has been elaborated. The most efficient
a
catalyst is the easily available and rather cheap Pd(OAc) (1 mol%)/
2
Entry
Catalytic system
Pd(OAc) /PPh
Base
Yield of 2b (%)
PCy (2 mol%) system. Homocoupling of various electron donating
3
1
2
3
4
5
6
7
8
9
CsF
CsF
CsF
CsF
CsF
KOH
52
51
72
71
78
72
56
31
41
and electron withdrawing substituted, sterically hindered aryl and
heteroaryl bromides and iodides can be performed in high yields.
The new protocol is suitable for homocoupling of aryl halides
bearing functional groups not tolerant to lithium, magnesium,
zincorganic reagents and strong bases. The proposed procedure has
a number of advantages: no solvent is used; aerobic conditions;
low catalyst loading; easily available base (CsF); the reaction is
activated with conventional heating (no milling, sonication, etc.
needed). Thus, we developed a versatile, highly efficient, step
economical, low waste (solventfree) procedure for the synthesis
of highly functionalized biaryls.
2
3
[Pd(PPh ) ]Cl
2
3
2
t
3
b
Pd(OAc) /PBu ·HBF
4
2
Pd(OAc) /SPhos
2
Pd(OAc) /DavePhos
2
t
Bu Indenyl(PCy )PdCl
3
t
t
Bu Indenyl(PCy )PdCl
Bu ONa
3
t
Bu Indenyl(IPr)PdCl
KOH
t
t
Bu Indenyl(IPr)PdCl
Bu ONa
a
Reaction conditions: 4bromotoluene (1 mmol), (Bu Sn) (0.5 mmol),
3
2
[
Pd] (0.01 mmol), ligand (0.02 mmol), base (1.5 mmol), neat, 110°C, 24 h.
b
t
3
mol% of PBu ·HBF as a ligand.
3 4
This study was supported by the Russian Science Foundation
(grant no. 171301076).
from moderate to good (entries 6–9). Since activation of such
systems requires strong bases, we used Bu ONa and KOH.
t
According to the results of optimization of a catalytic system,
the highest yield of target 4,4'bitolyl (87%) was provided by
simple and available Pd(OAc) /PCy (entry 6).
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi: 10.1016/j.mencom.2018.05.032.
2
3
Next, we studied the scope and limitations of the developed
†
procedure (Table 3). Under solventfree conditions Pd(OAc) /
References
2
PCy demonstrates high activity with respect to electron with
3
1
2
Y. Huang, L. Liu and W. Feng, ChemistrySelect, 2016, 1, 630.
(a) S. S. Zhu and T. M. Swager, Adv. Mater., 1996, 8, 497; (b) I. V.
Klimovich, F.A. Prudnov, L. N. Inasaridze, I. E. Kuznetsov,A. S. Peregudov
and P. A. Troshin, Mendeleev Commun., 2017, 27, 207.
drawing (1h,i,l) and electron donating substituted (1e,g,j),
sterically hindered (1c,e,l), and heterocyclic (1k) aryl bromides.
This catalytic system also provided high yields in homocoupling
of aryl iodides (1'b,e,f,h). However, homocoupling of mesityl
bromide bearing two orthosubstituents gave low yield of 2d.
Interestingly, some substrates bearing orthosubstituents (1c,e) give
higher yields than analogous parasubstituted substrates (1b,f).
3 X. Mei and C. Wolf, J. Am. Chem. Soc., 2006, 128, 13326.
4 J. Buter, D. Heijnen, C. Vila, V. Hornillos, E. Otten, M. Giannerini,
A. J. Minnaard and B. L. Feringa, Angew. Chem. Int. Ed., 2016, 55, 3620.
5
G. Bringmann, T. Gulder, T. A. Gulder and M. Breuning, Chem. Rev.,
011, 111, 563.
2
6
7
M. Sharpe, B. Jarvis and K. L. Goa, Drugs, 2001, 61,1501.
M. Berthod, G. Mignani, G. Woodward and M. Lemaire, Chem. Rev.,
Table 3 Homocoupling of aryl bromides 1 and iodides 1'.a
2
005, 105, 1801.
(
Het)aryl
Yield
(%)
(Het)aryl
halide
Yield
(%)
Entry
Product
Entry
Product
8 (a) J. K. Stille, Angew. Chem. Int. Ed., 1986, 25, 508; (b) L.C. Campeau
and K. Fagnou, Chem. Soc. Rev., 2007, 36, 1058.
halide
9
Palladium in Heterocyclic Chemistry, eds. J. J. Li and G. Gribble,
Elsevier, Amsterdam, 2006.
1
2
3
4
5
6
7
8
1a
1b
1'b
1c
2a
2b
2b
2c
2d
2e
2e
2f
92
87
83
94
11
80
81
65
9
10
11
12
13
14
15
16
1'f
1g
1h
1'h
1i
2f
51
64
2g
2h
2h
2i
1
0 (a) M. L. Berger, D. Maciejewska, J. J. Vanden Eynde, M. Mottamal,
·
>99
64
J. Zabi n´ ski, P. Ka z´ mierczak, M. Rezler, I. Jarak, I. Piantanida, G. Karminski
Zamola, A. Mayence, P. Rebernik, A. Kumar, M. A. Ismail, D. W. Boykin
and T. L. Huang, Bioorg. Med. Chem., 2015, 23, 4489; (b)Y. Yamaguchi,
N. Nishizono, D. Kobayashi, T.Yoshimura, K. Wada and K. Oda, Bioorg.
Med. Chem. Lett., 2017, 27, 2645; (c) Q. He, T. Li, C. Yan, Y. Liu,
J. Wang, M. Wang, Y. Lin and X. Zhan, Dyes Pigments, 2016, 128, 226;
1d
1e
>99
83
1j
2j
1'e
1f
1k
1l
2k
2l
69
68
(d) J. T. Henssler and A. J. Matzger, J. Org. Chem., 2012, 77, 9298;
a
Reaction conditions: aryl bromide or iodide (1 mmol), (Bu Sn) (0.5 mmol),
(e) J. I. Bruce, J.C. Chambron, P. Kölle and J.P. Sauvage, J. Chem. Soc.,
Perkin Trans. 1, 2002, 1226; (f) J. Mendiola, I. Castellote, J. Alvarez
Builla, J. FernándezGadea, A. Gómez and J. J. Vaquero, J. Org.
Chem., 2006, 71, 1254; (g) B. J. Morgan, X. Xie, P.W. Phuan and M. C.
Kozlowski, J. Org. Chem., 2007, 72, 6171; (h) T. Khanasa, N. Prachumrak,
R. Rattanawan, S. Jungsuttiwong, T. Keawin, T. Sudyoadsuk, T. Tuntulani
and V. Promarak, J. Org. Chem., 2013, 78, 6702; (i) J. M. Hancock, A. P.
Gifford, C. J. Tonzola and S. A. Jenekhe, J. Phys. Chem. C, 2007, 111,
6875; (j) C. J. Tonzola, M. M. Alam and S. A. Jenekhe, Macromolecules,
2005, 38, 9539; (k) L. E. Polander,A. S. Romanov, S. Barlow, D. K. Hwang,
B. Kippelen, T. V. Timofeeva and S. R. Marder, Org. Lett., 2012, 14, 918;
3
2
Pd(OAc) (0.01 mmol), PCy (0.02 mmol), CsF (1.5 mmol), neat, 110°C,
2
3
2
4 h.
Notably, in the first stage of the reaction, namely, halogen–
metal exchange, no lithium, magnesium, or zincorganic com
pounds (reagents in Murahashi,23 Kumada, Negishi coupling)
24
25
were used. In the second stage, coupling, no strong bases
26
27
(Suzuki–Miyaura, Hiyama coupling) were required. Thus, the
most prominent advantage of the developed SSHC protocol is
the possibility to obtain biaryls bearing reactive functional groups
not tolerant to RLi, RMgX, RZnX and strong bases (2h,i,l).
(l) T. Keawin, C. Sooksai, N. Prachumrak, T. Kaewpuang, D. Muenmart,
S. Namuangruk, S. Jungsuttiwong, T. Sudyoadsuk and V. Promarak,
RSC Adv., 2015, 5, 16422; (m) B. M. Bocknack, L.C. Wang, F. W.
Hughes and M. J. Krische, Tetrahedron, 2005, 61, 6266; (n) J. Khunchalee,
R. Tarsaeng, S. Jungsuttiwong, T. Keawin, T. Sudyoadsuk andV. Promarak,
Tetrahedron Lett., 2012, 53, 5939.
†
General procrdure. A screwcap vial equipped with a magnetic stir bar
was charged with aryl halide (1 mmol), hexanbutylditin (0.5 mmol),
palladium acetate (0.01 mmol) and tricyclohexylphosphine (0.02 mmol),
followed by anhydrous cesium fluoride (1.5 mmol). The resulting mixture
was manually homogenized with a magnet. A vial was transferred to a
preheated oil bath (110°C). After 24 h, the mixture was cooled, dissolved
in CH Cl –H O mixture (1:1), the organic phase was separated, the solvent
11 D. GarcíaCuadrado, A. M. Cuadro, J. AlvarezBuilla, U. Sancho, O. Castaño
and J. J. Vaquero, Org. Lett., 2006, 8, 5955.
12 Z. Zhao, Q. Ji,Y. Xia and X. Zhan, Chemistry Bulletin/Huaxue Tongbao,
2008, 71, 389.
13 C. Pan, M. Liu and X. Duan, Chin. J. Org. Chem., 2015, 35, 472.
14 (a) G. A. Chesnokov, M. A. Topchiy, P. B. Dzhevakov, P. S. Gribanov,
A. A. Tukov, V. N. Khrustalev, A. F. Asachenko and M. S. Nechaev,
2
2
2
was evaporated in vacuo and the product was isolated by flash chromato
graphy on a silica gel by elution with hexane–CH Cl mixture.
2
2
–
324 –