Synthesis of biaryls using the coupling reaction of diaryldimethyltins with copper(II) nitrate

Article abstract of DOI:10.1246/cl.2000.160

The coupling of diaryldimethyltins with Cu(NO₃)₂·3H₂O in THF proceeds smoothly at room temperature under ambient atmosphere to produce the corresponding biaryls in good to high yields. Diaryldimethyltins can be prepared in high yields by the reaction of aryllithiums with dichlorodimethyltin.

Full text of DOI:10.1246/cl.2000.160

160
Chemistry Letters 2000
Synthesis of Biaryls Using the Coupling Reaction of Diaryldimethyltins with Copper(II) Nitrate
Genta Harada, Masato Yoshida, and Masahiko Iyoda*
Department of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397
(Received November 1, 1999; CL-990929)
The coupling of diaryldimethyltins with Cu(NO3)2·3H2O
in THF proceeds smoothly at room temperature under ambient
atmosphere to produce the corresponding biaryls in good to
high yields. Diaryldimethyltins can be prepared in high yields
by the reaction of aryllithiums with dichlorodimethyltin.
Although a number of reactions have been reported for the
homocoupling of aromatic and heteroaromatic halides to pro-
duce biaryls and their heteroaromatic analogues,1,2 the
Ullmann reaction is believed to be the best method because of
its ease of operation.3 Previously, we reported an improved
Ullmann reaction using a copper(II)-mediated coupling of an
organozinc species to produce biphenylene and its derivatives.4
Recently, we have found another new improved method for the
synthesis of biaryls and their heteroaromatic analogues using
coupling product 3a in 69-85% yields (entries 4-6). A similar
reaction of dibutylbis(4-chlorophenyl)tin (2a) with
Cu(NO3)2·3H2O (2.2 equiv.) in THF at 23 °C produced 3a in
85% yield which was slightly lower than that of 1a (entry 7).
The coupling reaction needed 2 equiv. of Cu(NO3)2·3H2O, and
the reaction of 1a with 1 equiv. of Cu(NO3)2·3H2O gave 3a in
45% yield, together with the recovered starting material 1a.
On the basis of the results shown in Table 1, the coupling
reactions of various kinds of diaryldimethyltins with
Cu(NO3)2·3H2O were carried out (Table 2). As shown in
Table 2, the reactions of diaryldimethyltins with
Cu(NO3)2·3H2O in THF proceeded smoothly to produce
biaryls in good to high yields. Thus, the reaction of
dimethyldiphenyltin (1b) with Cu(NO3)2·3H2O in THF at 23
°C gave biphenyl (3b) in 97% yield (entry 2). Similar reac-
tions of diaryldimethyltins (1c-d, 1f-g, and 1i) containing
para- or meta-substituents produced the corresponding biaryls
in 78-95% yields (entries 3-4, 6-7, and 9). In the case of ortho-
substituted diaryldimethyltins, the reaction of dimethylbis(2-
methylphenyl)tin (1e) with Cu(NO3)2·3H2O gave 2,2'-
dimethylbiphenyl (3e) (entry 5) in 82% yield, whereas the
reaction of dimethylbis(2-methoxyphenyl)tin (1h) with
Cu(NO3)2·3H2O in THF was slow to produce 2,2'-dimethoxy-
biphenyl (3h) in 49% yield (entry 8). The reactions of
dimethylbis(thienyl)tins (4a and 4b) with Cu(NO3)2·3H2O
afforded bithiophenes (5a and 5b) in 62 and 68% yields,
respectively (entries 10 and 11).
the coupling of diaryldimethyltins with Cu(NO3)2·3H2O
(Scheme 1).
As shown in Scheme 1, the preparation of dialkyl-
diaryltins (1 and 2) was carried out starting from the corre-
sponding aryl bromides. Thus, the reaction of aryl bromides
with butyllithium (1.1 equiv.), followed by treatment with
dialkyldichlorotin (0.5 equiv.) afforded dialkyldiaryltins (1 and
2) in moderate to high yields [1a: R = 4-Cl, 85%; 1b: R = H,
93%; 1c: R = 4-Me, 90%; 1d: R = 3-Me, 76%; 1e: R = 2-Me,
83%; 1f: R = 4-OMe, 85%; 1g: R = 3-OMe, 49%; 1h: R = 2-
OMe, 80%; 1i: R = 3-Cl, 73%; 2a: R = 4-Cl, 80%;]. In a simi-
lar manner, the reaction of bromothiophenes with butyllithium,
followed by treatment with dichlorodimethyltin gave 4 in good
yields [4a: R = H, 2-thienyl, 81%; 4b: R = H, 3-thienyl, 72%].
The coupling reactions of dialkylbis(4-chloromethyl)tins
(1a and 2a) with Cu(NO3)2·3H2O are summarized in Table 1.
Although the known couplings of organotin compounds using
organometallic reagents can be carried out under an inert
atmosphere,5,6 the reaction of 1a with Cu(NO3)2·3H2O in THF
at 23 °C proceeded smoothly under ambient atmosphere or in
an atmosphere of oxygen to produce 4,4'-dichlorobiphenyl (3a)
in 91 and 88% yields, respectively (entries 1 and 2). A similar
reaction of 1a under nitrogen gave 3a in lower yield (entry 3).
The reaction rate of 1a with Cu(NO3)2·3H2O (2.2 equiv.) at 0
°C in THF was much slower than that at 23 °C to afford the
Although the reactions of tributylaryltin (Ar-SnBun ) with
Cu(NO3)2·3H2O, PdCl2(CH3CN)2, and [PdCl(π-C3H5)]32 were
reported to produce biaryls (3),6,7 the reaction of diaryl-
dimethyltins reported here gave higher yields of the products
(Table 2). In addition, the intramolecular coupling of diaryl-
dimethyltins with Cu(NO3)2·3H2O in THF can be carried out
without an inert atmosphere, and hence this coupling can be
widely employed for the construction of biphenyl frameworks
under ambient atmosphere or under oxygen.
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
161
The reaction reported here can be widely applied for the
synthesis of biaryls and heterobiaryls. Further studies on the
coupling reactions of diaryldialkyltins with transition metal
catalysts are now under way.
Financial support by a Grant-in-Aid for Scientific
Research on Priority Areas from the Ministry of Education,
Science, Sports and Culture, Japan (11119256) is gratefully
acknowledged.
References and Notes
1
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W. Knight, in "Coupling Reactions Between sp2 Carbon
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M. Trost and I. Fleming, Pergamon Press, London (1991),
Vol. 3, p. 499.
Interestingly, the reaction of bis(4-bromo-3-
thienyl)dimethyltin (6)8 with Cu(NO3)2·3H2O produced 4,4'-
dibromo-3,3'-bithiophene (7)9,10 in 76% yield (Scheme 2).
Similarly, the reaction of bis(4-bromo-3-furyl)dimethyltin and
bis(3-bromo-2-thienyl)dimethyltin (8 and 10)8 with
Cu(NO3)2·3H2O afforded 4,4'-dibromo-3,3'-bifuran and 3,3'-
dibromo-2,2'-bithiophene (9 and 11)9,10 in 72 and 52% yields,
respectively. These reactions gave selectively the coupling
products without loss of the bromo substituents.
2
For examples, see, a) D. J. Cram, M. deGrandpre, C. B.
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4
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We anticipated that the first step of the reaction of diaryl-
dimethyltins with Cu(NO3)2·3H2O involves an electron-trans-
fer process and transmetallation to afford an organocopper(II)
species and dimethyltin dinitrate as depicted in Scheme 3.
Since the reaction of a mixture of 1a (0.5 mmol) and 6 (0.5
mmol) with Cu(NO3)2·3H2O (2.2 mmol) in THF (2 ml) at
room temperature for 1 h produced 3a (26%) and 7 (25%) with
the corresponding cross-coupling product (30%), the interme-
diates for biaryls may be radical-like species which dimerizes
to produce the coupling products.
7
8
9
a) L. Alcaraz and R. J. K. Taylor, Synlett, 1997, 791. b) E.
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The compounds (6, 10, and 8) were prepared starting from
3,4- and 2,3-dibromothiophenes and 3,4-dibromofuran in
63, 59, and 65% yields, respectively.
S. Gronowitz, Acta Chem. Scand., 15, 1393 (1961).
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