Buchwald ligand-assisted Suzuki cross-coupling of polychlorobenzenes

Article abstract of DOI:10.1016/j.mencom.2021.04.039

Screening of four Buchwald ligands for the cross-coupling of isomeric di-, tri- and tetrachlorobenzenes with arylboronic acids revealed that good yields of exhaustive substitution can be best provided by 2-dicyclohexylphosphino-2′-(dimethylamino) biphenyl (DavePHOS).

Full text of DOI:10.1016/j.mencom.2021.04.039

Mendeleev
Communications
Mendeleev Commun., 2021, 31, 400–402
Buchwald ligand-assisted Suzuki cross-coupling of polychlorobenzenes
Andrei A. Vasil’ev,* Alexander S. Burukin, Galina M. Zhdankina and Sergei G. Zlotin
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow,
Russian Federation. Fax: +7 499 135 5328; e-mail: vasiliev@ioc.ac.ru
DOI: 10.1016/j.mencom.2021.05.039
Cln
Cln−m
Arn
Screening of four Buchwald ligands for the cross-coupling of
isomeric di-, tri- and tetrachlorobenzenes with arylboronic
acids revealed that good yields of exhaustive substitution can
be best provided by 2-dicyclohexylphosphino-2′-(dimethyl-
amino)biphenyl (DavePHOS).
ArBꢀOꢁꢂ2
ꢃPdꢄ
PCy2
Arm
Me
2N
Keywords: polychloroarenes, biaryls, cross-coupling, arylboronic acids, Buchwald ligands.
Polychloroarenes (PCAs) are the environmentally hazardous
materials. The mostly recognized means for their chemical utili-
zation is catalytic hydrogenolysis of the C–Cl bonds.1 However,
chemical value of thus prepared aromatic hydrocarbons is not
great as such compounds are generally accessed by cheaper and
simpler ways. On the other hand, PCAs seem prospective starting
materials for the preparation of potentially useful substances if
the transformations of poorly reactive C-Cl bonds into C-C or
C-heteroatom ones become easy to accomplish. The chemical
properties of PCAs were systematized in reviews.2,3
The first efforts to attain the cross-coupling diversity for chloro-
arenes, in particular PCAs, were based on the Kumada reactions
involving organomagnesium counterparts while other cases of C–C
coupling were scarce (see review3). The product yields were mostly
moderate. In the middle of 2000s, PCAs were subjected to the
Suzuki coupling with phenylboronic acid in the presence of
palladium source, Pd(dba)2 or Pd(OAc)2, in combination with
PBut3 as the ligand4 or imidazolium salts.5 The reactions could
be also carried out under ligand-free conditions.6,7 In all these
studies, good preparative results were rarely achieved due to
incomplete conversion, low selectivity and undesired parallel
hydrodechlorination.
for the Suzuki performance. Several reports on the Suzuki
coupling of PCAs have emerged.10-12 Very promising results
with PCAs were delivered using 2-dicyclohexylphosphino-2′,6′-
dimethoxybiphenyl L1 (S-PHOS) as the ligand.12 However, the
authors12 disclosed no information on catalytic behavior of other
Buchwald-type ligands in the PCA coupling reactions. To remove
this gap, we decided herein to examine several other available
phosphine ligands, in particular, compounds L2–L4 in such
reactions. Previously,13 we successfully employed catalytic system
Pd(OCOCF3)2 /L1 for the Suzuki coupling of some mono- and
polychloroarenes in supercritical carbon dioxide.
In this work, the most experiments were carried out based on
reported conditions of the Buchwald procedure,8(a) namely,
Pd(OAc)2 /ligand molar ratio of 1:2, K3PO4, toluene, 90°C,
7-8 h.† The ligand tests were performed using 1,2,4,5-tetra-
chlorobenzene 1a as the model substrate (Scheme 1, Table 1). In
our hands (entry 1), the results with the use of S-PHOS (L1)
were not as good as documented in the comprehensive study.12
Under the similar conditions, ligand L2 [DavePHOS, 2-dicyclo-
hexylphosphino-2′-(dimethylamino)biphenyl] provided the highest
conversion of PCA 1a (see Table 1, entries 1, 2, 6, 8), with the
use of 1.1 equiv. PhB(OH)2 the monosubstitution product 2
having been formed with the good chemoselectivity (entry 2).
When potassium phosphate was used as the base, contribution of
side hydrodechlorination was regularly insignificant. In case of
potassium methoxide possessing reductive properties, the cross-
coupling was accompanied by the exhaustive hydrodechlorination
Within the past decades, the efficient catalytic systems suitable
for cross-coupling of non-activated chloroarenes have been
suggested. In particular, the Buchwald systems8,9 comprising
palladium source and special sterically hindered tertiary
biphenyl-2-ylphosphines proved very efficient and convenient
†
OMe
General procedure for the cross-coupling [cf. ref. 8(a)]. A 10 ml Schlenk
PCy2
PCy2
tube equipped with a stirring bar was charged with Pd(OAc)2 (7 mg,
0.03 mmol), ligand L1-L4 (0.06 mmol), PCA (0.5 mmol), PhB(OH)2
(66 mg, 0.55 mmol) and K3PO4 (339 mg, 1.6 mmol), and then capped
with a rubber septum. Air was removed by triple evacuation and filling
with argon. Deaerated toluene (1 ml) was then injected. The reaction was
processed at 85-90°C for ca. 7 h. A heterogeneous aliquot was mixed
with more toluene (~1:10), filtered through a short pad of silica, and the
filtrate was analyzed by GC-MS.
For exhaustive arylation of tri- and tetrachlorobenzenes (0.25 mmol),
Pd(OAc)2 (4 mg, 0.018 mmol), ligand L2 (14 mg, 0.036 mmol),
ArB(OH)2 (1.65 mmol) and K3PO4 (492 mg, 2.32 mmol) were applied.
For preparative isolation and product identification, see Online
Supplementary Materials.
Me
Me
2N
O
ꢀꢁ
ꢀꢂ
ꢀꢄ
PBu2t
PCy2
ꢀꢃ
© 2021 Mendeleev Communications. Published by ELSEVIER B.V.
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
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Mendeleev Commun., 2021, 31, 400–402
Ph
Cl
Ph
Ph
PhBꢀOꢋꢄ2
Cꢊꢋ2Cl2Ph2
Cꢊꢋ2ClPhꢍ
Cl
Ph
Cl
Cl
Ph
Cl
i
ꢁ
ꢂa ꢀꢁꢂꢃꢄ
Cl
Cl
Cl
Ph
Ph
Ar
Cl
Cl
Cl
Ph
Ar
ArBꢀOꢋꢄ2
PhBꢀOꢋꢄ2
ꢀa
i
Ph
Ar
Ar
ꢂ'aꢅ ꢂ''a ꢀꢆ100ꢃꢄ
ꢀb
ꢂb ꢀꢇꢇꢃꢄ
ꢂ'a Ar ꢈ ꢂꢉMeOCꢊꢋꢂ
ꢂ''a Ar ꢈ 2ꢅꢂꢉꢌ2Cꢊꢋꢍ
Scheme 1 Reagents and conditions: i, Pd(OAc)2, ligand L2, K3PO4, PhMe, 90°C, 7-8 h.
Table 1 Optimization of the cross-coupling of 1,2,4,5-tetrachlorobenzene 1a with PhB(OH)2 assisted by ligands L1-L4.a
Product composition (GC-MS) (mol%)
Entry
Ligand
PhB(OH)2 (equiv.) Base
Coupling productsb
tri-
unreacted 1a
mono- 2
di-
tetra- 3a
-
-
-
-
6
-
-
-
-
94
-
47
-
10
1
2
3
4
5
6
7
8
9
L1
L2
L2
L2
L2
L3
L3
L4
L4
1.1
K3PO4
22 + (1 + 1)
7 + 4 + 7
0.4 + 0.6
(5 + 5 + 9)
22 + 17 + 34 + (2)
-
4 + 4 + 6
2 + 2 + 5
1 + 2
55 + (3)
1.1
1.1c
K3PO4
MeOK
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
97
2
-
-
-
(81)
20 + (5)
-
45 + (1 + 1)
-
2.5
6.6d
1.1
1 + 6
40 + (4)
-
31 + (1)
-
60 + (4)
2
6.6d
1.1
6.6d
32 + (1)
29 + (2)
4 + 11 + 32
10
a Conditions: 6 mol% of Pd(OAc)2, 12 mol% of L1-L4, K3PO4 (1.5-3 equiv. to PhB(OH)2), PhMe, 90°C, 7-8 h. b Parentheses relate to hydrodechlorinated
analogues. c In dioxane. d 7.2 mol% of Pd(OAc)2, 14.4 mol% of the ligand.
(entry 3). Raising the amount of the cross-counterpart to 2.5 equiv.
provided the growth for the fraction of disubstitution products
(entry 4). When this parameter reached value of 6.6 equiv.,
1,2,4,5-tetraphenylbenzene 3a was formed in the analytical yield
of94%(entry5).Undertheseconditions,relative1,2,4,5-tetraaryl-
benzenes 3′a and 3′′a were obtained in good yields (see Scheme 1).
Isomeric 1,2,3,4-tetraphenylbenzene 3b was also synthesized from
the corresponding precursor 1b in a yield of 88% (the rest 12%
were the isomeric Ph3C6H2Cl). However, two other tested ligands
L3 and L4 appeared much less efficient promotors for the cross-
coupling between 1,2,4,5-tetrachlorobenzene 1a and PhB(OH)2
under optimal conditions [7.2 mol% Pd(OAc)2, 14.4 mol% of a
ligand, K3PO4] than ligand L2 affording regioisomeric mixtures
of products of incomplete conversion (see Table 1, entries 6-9).
The proposed L2-based catalytic system proved to be very
efficient in arylation reactions of isomeric trichlorobenzenes 4a-c
with phenylboronic acid (5 equiv.) to produce the corresponding
triphenylbenzenes 5a-c in nearly quantitative yields (Scheme 2).
Less active dichlorobenzenes 4d-f in reaction with excess
PhB(OH)2 (3 equiv.) gave mixtures of mono- and disubstitution
products. Luckily, their full conversion into terphenyls 5d-f was
achieved on replacement of potassium phosphate with more basic
hydroxide.
ratio, each group was comprised of regioisomers and some
hydrodechlorination by-products. Hexaphenylbenzene was never
detected in these experiments. These results do not contradict
those of the study12 where C6Cl6 was transformed into C6Ph6 in
moderateyieldwiththeuseofcatalyticsystemPdCl2(MeCN)2 /L1
and with the very prolonged processing (the preparative yields of
C6Ph6 were achieved on moving to more active hexabromo-
benzene).
R1
R1
i ꢂfor ꢀa−cꢃ
or ii ꢂfor ꢀd−fꢃ
R2
Rꢁ
R2
Rꢁ
Cl
Ph
Rꢀ
Rꢀ
ꢀa−f
ꢁa−f ꢂꢄꢀ−100ꢅꢃ
a R1 ꢆ R2 ꢆ Clꢇ Rꢁ ꢆ Rꢀ ꢆ ꢈ
b R1 ꢆ Rꢁ ꢆ Clꢇ R2 ꢆ Rꢀ ꢆ ꢈ
c R1 ꢆ Rꢁ ꢆ ꢈꢇ R2 ꢆ Rꢀ ꢆ Cl
d R1 ꢆ Clꢇ R2 ꢆ Rꢁ ꢆ Rꢀ ꢆ ꢈ
e R1 ꢆ Rꢁ ꢆ Rꢀ ꢆ ꢈꢇ R2 ꢆ Cl
f R1 ꢆ R2 ꢆ Rꢀ ꢆ ꢈꢇ Rꢁ ꢆ Cl
a R1 ꢆ R2 ꢆ Phꢇ Rꢁ ꢆ Rꢀ ꢆ ꢈ
b R1 ꢆ Rꢁ ꢆ Phꢇ R2 ꢆ Rꢀ ꢆ ꢈ
c R1 ꢆ Rꢁ ꢆ ꢈꢇ R2 ꢆ Rꢀ ꢆ Ph
d R1 ꢆ Phꢇ R2 ꢆ Rꢁ ꢆ Rꢀ ꢆ ꢈ
e R1 ꢆ Rꢁ ꢆ Rꢀ ꢆ ꢈꢇ R2 ꢆ Ph
f R1 ꢆ R2 ꢆ Rꢀ ꢆ ꢈꢇ Rꢁ ꢆ Ph
The Pd(OAc)2 /L2 catalyzed reaction of hexachlorobenzene
with excess (8.6 equiv.) PhB(OH)2 afforded a mixture of tri-,
tetra- and pentaphenylated benzene derivatives in a 10:70:20
Scheme 2 Reagents and conditions: i, PhB(OH)2 (5 equiv.), Pd(OAc)2,
ligand L2, K3PO4, PhMe, 90°C, 7-8 h; ii, PhB(OH)2 (3 equiv.), Pd(OAc)2,
ligand L2, KOH, PhMe, 90°C, 7-8 h.
– 401 –

Mendeleev Commun., 2021, 31, 400–402
6 A. S. Burukin, A. A. Vasil’ev, N. L. Merkulova, M. I. Struchkova and
In conclusion, we have compared several Buchwald ligands
L1–L4 in the Suzuki cross-coupling of non-activated polychloro-
arenes with arylboronic acids. Among the ligands tested, 2-di-
cyclohexylphosphino-2′-(dimethylamino)biphenyl (DavePHOS)
provided the best results, quantitatively converting di-, tri- and
tetrachlorobenzenes into the corresponding polyarylbenzenes.
Some recent catalytic systems and reactants14 may also represent
good challenge for employing toward PCAs.
S. G. Zlotin, Russ. Chem. Bull., Int. Ed., 2006, 55, 118 (Izv. Akad. Nauk,
Ser. Khim., 2006, 114).
7 A. S. Burukin, PhD Thesis, 2006.
8 (a) J. P. Wolfe, R. A. Singer, B. H. Yang and S. L. Buchwald, J. Am.
Chem. Soc., 1999, 121, 9550; (b) J. P. Wolfe, H. Tomori, J. P. Sadighi,
J.Yin and S. L. Buchwald, J. Org. Chem., 2000, 65, 1158; (c) J. E. Milne
and S. L. Buchwald, J. Am. Chem. Soc., 2004, 126, 13028; (d) T. E. Barder,
S. D. Walker, J. R. Martinelli and S. L. Buchwald, J. Am. Chem. Soc.,
2005, 127, 4685.
9 R. Martin and S. Buchwald, Acc. Chem. Res., 2008, 41, 1461.
10 D.-H. Lee and M.-J. Jin, Org. Lett., 2011, 13, 252.
11 T. Tu, Z. Sun, W. Fang, M. Xu and Y. Zhou, Org. Lett., 2012, 14, 4250.
12 S. Reimann, P. Ehlers, M. Sharif, A. Spannenberg and P. Langer,
Tetrahedron, 2016, 72, 1083.
Scientific Schools Development Program by Zelinsky
Institute of Organic Chemistry is gratefully acknowledged.
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi: 10.1016/j.mencom.2021.05.039.
13 I. V. Kuchurov, A. A. Vasil’ev and S. G. Zlotin, Mendeleev Commun.,
2010, 20, 140.
14 (a) P. S. Gribanov, G. A. Chesnokov, P. B. Dzhevakov, N. Yu. Kirilenko,
S. A. Rzhevskiy, A. A. Ageshina, M. A. Topchiy, M. V. Bermeshev,
A. F. Asachenko and M. S. Nechaev, Mendeleev Commun., 2019, 29, 147;
(b) S. B. Soliev, A. V. Astakhov, D. V. Pasyukov and V. M. Chernyshev,
Russ. Chem. Bull., Int. Ed., 2020, 69, 683 (Izv. Akad. Nauk, Ser. Khim.,
2020, 683); (c) E. V. Verbitskiy, E. M. Dinastiya, O. S. Eltsov,
E. F. Zhilina, A. V. Schepochkin, G. L. Rusinov, O. N. Chupakhin
and V. N. Charushin, Mendeleev Commun., 2020, 30, 142;
(d) E. S. Matyugina, A. L. Khandazhinskaya, S. N. Kochetkov and
K. L. Seley-Radtke, Mendeleev Commun., 2020, 30, 231.
References
1 (a) J. B. Hoke, G. A. Gramiccioni and E. N. Balko, Appl. Catal., B, 1992,
1, 285; (b) F. Murena and E. Schioppa, Appl. Catal., B, 2000, 27, 257;
(c) Y. Ukisu, S. Iimura and R. Uchida, Chemosphere, 1996, 33, 1523;
(d) S. Zinovyev, A. Perosa, S. Yufit and P. Tundo, J. Catal., 2002, 211, 347.
2 (a) Polychloroaromatic Compounds, ed. H. Suschitzky, Plenum Press,
NewYork, 1974; (b) T. N. Gorbunova, V. I. Saloutin and O. N. Chupakhin,
Russ. Chem. Rev., 2010, 79, 511 (Usp. Khim., 2010, 79, 565).
3 A. A. Vasil’ev, A. S. Burukin and S. G. Zlotin, Russ. Chem. Rev., 2007,
76, 885 (Usp. Khim., 2007, 76, 947).
4 A. S. Burukin, A. A. Vasil’ev, A. O. Chizhov and S. G. Zlotin, Russ.
Chem. Bull., Int. Ed., 2005, 54, 970 (Izv. Akad. Nauk, Ser. Khim., 2005, 947).
5 A. S. Burukin, A. A. Vasil’ev, N. L. Merkulova, A. O. Chizhov,
E. A. Mistryukov and S. G. Zlotin, Russ. Chem. Bull., Int. Ed., 2007, 56,
1467 (Izv. Akad. Nauk, Ser. Khim., 2007, 1414).
Received: 11th February 2021; Com. 21/6450
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