Vanadium(IV) tetrachloride catalyzed oxidative homo-coupling of aryl lithium under mild reaction condition

Article abstract of DOI:10.1016/j.tetlet.2012.03.011

A novel efficient strategy to prepare symmetrical diaryls via VCl ₄ catalyzed homo-coupling of aryl lithium has been developed. In which, organometallic reagent n-BuLi was applied as the strong base to form aryl lithium from aryl halogen in anhydrous diethyl ether, then it was followed by the addition of catalytic amount of VCl₄ at room temperature to afford diaryls. All the diaryls have been characterized by ¹H and ¹³C NMR.

Full text of DOI:10.1016/j.tetlet.2012.03.011

Tetrahedron Letters 53 (2012) 2444–2446
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Vanadium(IV) tetrachloride catalyzed oxidative homo-coupling
of aryl lithium under mild reaction condition
Feng Lu
Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse 35032, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel efficient strategy to prepare symmetrical diaryls via VCl4 catalyzed homo-coupling of aryl lithium
has been developed. In which, organometallic reagent n-BuLi was applied as the strong base to form aryl
lithium from aryl halogen in anhydrous diethyl ether, then it was followed by the addition of catalytic
amount of VCl4 at room temperature to afford diaryls. All the diaryls have been characterized by 1H
and 13C NMR.
Received 6 February 2012
Revised 29 February 2012
Accepted 2 March 2012
Available online 9 March 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Vanadium tetrachloride
n-BuLi
Homo-coupling
Aryllithium
Diaryl
1) n-BuLi / Et2O
2) VCl4, rt
Carbon–carbon bond formation of aryl–aryl by homo-/cross-
coupling reactions has been extensively investigated for decades
in order to develop highly efficient and environmentally friendly
strategies, as well as the construction of pharmaceuticals, natural
products, and new materials.1 Ullmann reaction as a convenient
method has been widely applied to prepare aryl–aryl complexes.2
Especially, palladium/nickel complexes—transition-metal oxidants
catalyzed oxidative homo-coupling of aryl-metal reagents has of-
fered symmetrical biaryl backbones, for example, Suzuki reaction
(aryl boronic acid),3 Sonogashira reaction (aryl stannanes),4 and
arylzinc.5 Recently, the iron-catalyzed homo-coupling reaction of
aryl Grignard reagent has attracted the profound interest from syn-
thetic chemists, for example, in the presence of a stoichiometric
amount of 1,2-dichloroethane.6 However, iron-catalyzed aryl mag-
nesium method was not well available for the low activity of chlo-
robenzene. Additionally, aryl magnesium also could be oxidized by
oxygen or alternative organic molecules to perform homo-coupling
reaction and generate diaryl,7 such as TiCl4.8 Oxovanadium(V) cat-
alytic activity has been investigated, though.9 Moreover, vana-
dium(III) reagent VCl3 has been performed to catalyze homo-
coupling of aryl bromide in the presence of two stoichiometric
amounts of Mg in THF with moderate yield.6 Cp2VCl2 catalyzed
meso-selective pinacol coupling reaction has also been reported.10
However, VCl4 as catalyst for homo-coupling of aryl lithium has
not been reported so far.11 In order to investigate the catalytic
activity of VCl4, and solve the low activity of aryl chloride via aryl
Br
MeO
MeO
OMe
Scheme 1. VCl4 catalyzed aryl lithium oxidative homo-coupling.
Grignard reagent method, as well as avoid the usage of organic oxi-
dant and precious transition metal catalyst, herein an efficient and
convenient method involving vanadium(IV) tetrachloride as cata-
lyst for oxidative homo-coupling of aryl lithium to prepare diaryls
has been developed under mild reaction condition (Scheme 1).
Neither stoichiometric transition-metal, nor oxidant, such as oxy-
gen, 1,2-dihalogen compounds, was required.
Commercially available red-brown liquid VCl4 was directly
applied as homogeneous catalyst in diethyl ether at room temper-
ature. The general procedure is described as follows.12 Under dried
dinitrogen atmosphere, aryl halogen was treated with equiv n-BuLi
in anhydrous diethyl ether for one hour to result in aryl lithium.
The reaction period depended on the activity of aryl halogen, for
example, aryl chloride with further one hour. After the addition
of catalytic amount of VCl4, the mixture was stirred at rt for hours
to afford the symmetrical diaryls. The coupling reaction was mon-
itored by thin layer chromatography till completion or no obvious
changing. The moderate yields could be partially ascribed to trace
H2O in commercial aryl halogens, which have not been dried or
freshly distilled. As Table 1 showed, electron-donating group led
to better yield, such as OCH3 (Table 1, entries 1, 7). In the absence
of n-BuLi, the mixture of phenyl bromide with VCl4 did not result in
biphenyl even after stirring for 24 h at room temperature. Also, it is
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http://dx.doi.org/10.1016/j.tetlet.2012.03.011

F. Lu / Tetrahedron Letters 53 (2012) 2444–2446
2445
Table 1
Preparation of diaryls catalyzed by VCl4 in diethyl ether at room temperaturea
Entry
ArX
Product
Time (h)
12
Yieldb (%)
CH3O
1
CH3O
OCH3
OCH3
72
Br
Br
c
2
3
12
24
12
12
10
10
10
12
12
64
Br
Br
I
d
CH3O
CH3O
0
4
70
68
81
86
80
61
63
5
Br
6
CH3O
7
CH3O
OCH3
I
8
I
9
Cl
10
Cl
a
b
c
Reaction condition: aryl halogen (4 mmol), n-BuLi (4 mmol), diethyl ether (20 ml), VCl4 (10 mg, 1%), room temperature.
Isolated yield.
Reaction condition: metal lithium (28 mg, 4 mmol), phenyl bromide (0.5 ml, 4 mmol), Et2O (20 ml), room temperature 2 h; VCl4 (10 mg), 12 h.
No n-BuLi, only VCl4 with aryl bromide.
d
common that treatment of phenyl bromide with n-BuLi only af-
fords phenyllithium, rather than diaryls. Therefore, the limitations
of requirement of electronically activated aryl iodide precursors
and a stoichiometric amount of transition metal salts have been
overcome. This methodology has been proved to be applicable to
construct symmetrical diaryls from various aryl halogen sub-
strates. Especially, this method made it possible to generate aryl
lithium reagents from electronically deactivated aryl chloride un-
der mild reaction condition. Although, in consideration of high
reactivity of n-BuLi, the substrates bearing active functional groups
such as –OH, –CHO, –CN, –COOEt etc. have not been attempted yet.
Additionally, there is no alternative oxidant required in the cata-
lytic process, for example, ClCH2CH2Cl, or oxygen.
A tentative mechanism is proposed as Scheme 2. According to
the catalytic mechanism of vanadium(V) complexes (VO(OR)2Cl)
and related investigations of VCl4 with n-BuLi,9 VCl4 was assumed
to firstly form active [V(III)] intermediate with n-BuLi, which then
conducted oxidative addition with aryl bromide to generate
Ar[V(V)]Br. It was followed by transmetalation with Ar-Li to result
in LiBr and Ar[V(V)]Ar. Reductive elimination of Ar[V(V)]Ar affor-
ded diaryls and active substrate [V(III)]. Solid evidence related to
the intermediates should be carried out, though.
Interestingly, metallic lithium used as lithiation reagent has
also been successfully demonstrated by reaction with phenyl bro-
mide (entry 3), though the yield was not so satisfactory. The de-
tailed procedure was described as below. At room temperature,
the mixture of equiv aryl bromide and metal lithium wire was stir-
red for hours till solid metal disappeared, then it was followed by
the addition of catalytic amount of VCl4 to give biphenyl after
hours’ vigorously stirring at rt and purification by flash
chromatography.
The advantages of this strategy are obvious, available for aryl
chloride, mild reaction condition, as well as no application of
expensive transition metal and organic ligands. Also, there is no
necessity to prepare organoborate via aryl bromide with n-BuLi.13
The optimization including catalytic loading, reaction temperature,
time, and solvents, will be considered further. While the expansion
scope of this new methodology to alkyl lithium substrates, mixed
aryl halogen, bicyclic aromatic systems such as naphthalene sub-
strates, as well as metallic lithium as lithiation reagent, are under
the way.
In conclusion, an efficient and versatile strategy to prepare sym-
metrical biaryls via vanadium(IV) tetrachloride catalyzed oxidative
homo-coupling of aryl lithium has been successfully demonstrated
for the first time. In which, n-BuLi was used as the lithiation re-
agent to prepare aryl lithium, and catalytic amount of vana-
dium(IV) tetrachloride was involved in oxidative homo-coupling
of aryl lithium to afford symmetrical biaryls at room temperature.
Importantly, this method overcame the drawback of the prepara-
tion of Grignard reagent from low active aryl chloride. Specially,
no stoichiometric amount of transition-metal or organic oxidant
is required. This method allows an easy and practical way for the
construction of symmetrical aryl–aryl.
n-BuLi
VCl4
[V]III
Ar-Ar
Ar-Br
Ar-[V]V-Ar
LiBr
Ar-[V]V-Br
n-BuLi
Ar-Br
Ar-Li
Scheme 2. Proposed mechanism for VCl4 catalyzed aryllithium oxidative homo-
coupling.

2446
F. Lu / Tetrahedron Letters 53 (2012) 2444–2446
9. (a) Ishikawa, T.; Ogawa, A.; Hirao, T. Organometallics 1998, 17, 5713–5716; (b)
Acknowledgments
Hirao, T. Coord. Chem. Rev. 2003, 237, 271–279; (c) Reddy, P. P.; Chu, C.; Hwang,
D.; Wang, S.; Uang, B. Coord. Chem. Rev. 2003, 237, 257–269.
It is gratefully acknowledged for generous supports from Pro-
fessor Dr. Chris Elschenbroich and Department of Chemistry of
the University of Marburg, Germany.
10. (a) Hirao, T.; Takeuchi, H.; Ogawa, A.; Sakurai, H. Synlett 2000, 11, 1658–1660;
(b) Hirao, T.; Hatano, B.; Imamoto, Y.; Ogawa, A. J. Org. Chem. 1999, 64, 7665–
7667; (c) Hirao, T.; Asahara, M.; Muguruma, Y.; Ogawa, A. J. Org. Chem. 1998,
63, 2812–2813; (d) Hatano, B.; Ogawa, A.; Hirao, T. J. Org. Chem. 1998, 63,
9421–9424.
11. (a) Ragan, M. A. Can. J. Chem. 1985, 63, 291–293; (b) O’Brien, M. K.; Vanasse, B.
Vanadium(IV) Chloride. In Encyclopedia of Reagents for Organic Synthesis;
Paquette, L., Ed.; J. Wiley & Sons: New York, 2004.
12. General Procedures, 4,4’-Dimethoxybiphenyl: All the reactions were performed
under dinitrogen atmosphere with standard Schlenk techniques. At 0 °C, to the
solution of bromoanisole (0.5 ml, 4 mmol) in anhydrous Et2O (20 ml), n-BuLi
(1.6 M/hexane, 2.5 ml, 4 mmol) was added dropwise. After stirred at rt for 1 h,
References and notes
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red liquid VCl4 (5.5 ll, 10 mg, 0.052 mmol, 1.3%) was added. The mixture was
stirred at rt for further 12 h. During this period, the reaction mixture was
monitored by TLC till completion or no significant changing. After all the
volatiles were evaporated in vacuum, the residue was extracted by petroleum
ether and purified by flash chromatography (SiO2) to give the desired product
as white powder. Yield: 310 mg (72%). 1H NMR (300 MHz): d 7.41 (d, J = 3 Hz,
4H), 6.88 (d, J = 3 Hz, 4H), 3.77 (s, 6H). 13C NMR: 156.9, 131.9, 126.1, 112.7, 54.
13. Mizuno, H.; Sakurai, H.; Amaya, T.; Hirao, T. Chem. Commun. 2006, 5042–5044.