Reductive coupling of aryl bromides using cat. Pd/TDAE system in ionic liquids

Article abstract of DOI:10.1246/cl.2005.530

Pd/TDAE-promoted reductive coupling of aryl bromides (Ar-Br) proceeded in ionic liquids, e.g., BdmimBF₄ and BdmimTf₂N, to afford the corresponding symmetric biaryls (Ar-Ar) in good yields. Proper choice of ionic liquids and Pd catalysts is indispensable. Recycle use of BdmimTf₂N and Pd catalyst was performed successfully. Copyright

Full text of DOI:10.1246/cl.2005.530

530
Chemistry Letters Vol.34, No.4 (2005)
Reductive Coupling of Aryl Bromides Using Cat. Pd/TDAE System in Ionic Liquids
Manabu Kuroboshi, Toshiyuki Takeda, Ryota Motoki, and Hideo Tanakaꢀ
Department of Organic Chemistry, Faculty of Engineering, Okayama University,
Tsushima-naka 3-1-1, Okayama, 700-8530
(Received January 5, 2005; CL-050009)
Pd/TDAE-promoted reductive coupling of aryl bromides
Finally, reductive elimination of 6 would produce biaryl Ar–Ar 2
and Pd(0) species to complete the catalytic cycle (Step 5).
BmimBF4 and BmimPF6 would form Pd-carbene complex 37
to retard the desired catalytic cycle. Methyl group at the 2-posi-
tion of Bdmimþ ion would prevent the formation of the carbene
complex.
(Ar–Br) proceeded in ionic liquids, e.g., BdmimBF4 and
BdmimTf2N, to afford the corresponding symmetric biaryls
(Ar–Ar) in good yields. Proper choice of ionic liquids and Pd
catalysts is indispensable. Recycle use of BdmimTf2N and Pd
catalyst was performed successfully.
PdCl (PhCN)
2
2
Development of environmentally benign organic synthesis
has been a keen project, and environmentally friendly solvents
such as water,1 supercritical CO2,2 and ionic liquids (ILs)3 have
been intensively investigated. Recently, we reported that Pd/tet-
rakis(dimethylamino)ethylene (TDAE) promoted reductive cou-
pling of Ar–Br in DMF to give a symmetrical biaryl Ar–Ar.4
Herein, we describe that the Pd/TDAE-promoted reductive cou-
pling of Ar–Br in ILs proceeded smoothly by the proper choice
of the Pd catalyst and the ILs (Eq 1).5 The recycle use of the Pd
catalyst and the ILs is also discussed.
TDAE
[Step 1]
2+
TDAE
[Step 5]
Pd(0)
[Step 2]
[Step 3]
Ar-X (1)
Ar-Ar (2)
II
II
Ar Pd X (4)
(6)
Ar Pd Ar
TDAE
-
X
0 -
[Ar-Pd ]
[Step 4]
2+
TDAE
Ar-X (1)
(5)
Scheme 1. A plausible mechanism.
Me
cat. PdCl (PhCN) , TDAE
2
2
(1)
2
Ar Br
Ar Ar
Ionic Liquid, 60 °C
1
A typical procedure is as follows: To a solution of methyl p-
2
Bu
N
N
Pd
bromobenzoate (1a, 1 mmol) in 1-butyl-2,3-dimethylimidazoli-
um tetrafluoroborate (BdmimBF4, 2 mL) containing a catalytic
amount of PdCl2(PhCN)2 (0.05 mmol) was added TDAE
(2 mmol). After being stirred under argon atmosphere at 60 ꢁC,
the mixture was extracted with Et2O. Evaporation of the solvent
of the Et2O extracts followed by column chromatography (SiO2,
Hexane/EtOAc = 5/1) afforded 4,40-bis(methoxycarbonyl)-
biphenyl (2a) in 72% yield.
The reductive coupling of p-bromoanisole (1b) proceeded
similarly to give 4,40-dimethoxybiphenyl (2b) in 68% yield.
Biaryls 2a and 2b were obtained in 87 and 69% yields,
respectively, in 1-butyl-2,3-dimethylimidazolium bis(trifluoro-
methanesulf)imide (BdminTf2N). In contrast, the coupling did
not occur in 1-butyl-3-methylimidazolium tetrafluoroborate
(BmimBF4) and 1-butyl-3-methylimidazolium hexafluorophos-
phate (BmimPF6).
Proper choice of Pd catalysts is also indispensable.6 p-Bro-
moanisole (1b) afforded biphenyl 2b in 68, 46, and 39% yields
with PdCl2(PhCN)2, PdCl2, and Pd(OAc)2, respectively. 4-Cya-
nobromobenzene (1c) gave 4,40-dicyanobiphenyl (2c) in 83 and
73% yield with PdCl2(PhCN)2 and Pd(OAc)2, respectively.
From these results, PdCl2(PhCN)2 gave the best results. Nickel
catalyst, e.g., NiBr2(bpy), was not effective for this reaction.
A plausible mechanism of the reductive coupling reaction is
shown in Scheme 1. Pd(II) would be reduced with TDAE to gen-
erate Pd(0) species (Step 1). Oxidative addition of Ar–X (1) to
the Pd(0) would form Ar–PdII–X 4 (Step 2), which would be,
in turn, reduced with TDAE to give [Ar–Pd0]ꢂ 5 (Step 3). Sub-
sequent reaction of 5 with 1 would afford Ar–PdII–Ar 6 (Step 4).
N
N
Bu
Me
3
In a similar manner to that described above, the Pd/TDAE-
promoted reductive coupling of various Ar–Br in BdmimBF4
was examined (Table 1). Ar–Br having an electron-donating
group (EDG), such as MeO (1b), Me2N (1d), Me (1e), and
EtCH(OH) (1f) groups, at p-position gave the corresponding
biaryls 2b, 2d, 2e, and 2f in 53–80% yields, respectively (En-
tries 1–4). The coupling of 2-bromotoluene (1g) did not proceed
probably owing to steric hindrance of methyl group (Entry 5).
The reductive coupling of Ar–Br having an electron-with-
drawing group (EWG) proceeded more efficiently than that hav-
ing an EDG;8 indeed, the coupling reaction of Ar–Br having
EWG, such as MeOCO (1a), BuOCO (1h), EtCO (1i), and CN
(1c, 1j) groups, at p- or m-position completed within 2–3 h to
give the corresponding biaryls 2a, 2h, 2i, 2c, and 2j in 68–
83% yields (Entries 6–10). o-Cyanobromobenzene (1k) gave
2k in 80% yield after 6 h (Entry 11). To be compared with 1g,
1k would be activated by EWG, e.g., CN group, and steric hin-
drance of CN group would much smaller than that of Me group.
Therefore, the coupling of 1k proceeded but completed after
rather long reaction time.
In the coupling of the substrate having an easily reducible
functional groups, such as HCO and NO2 groups, over-reduction
of these functional groups would take place. Indeed, the cou-
pling of 4-bromobenzaldehyde (1l) gave the corresponding biar-
yl 2l in only 19% yield, though the substrate 1l was consumed
Copyright Ó 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.4 (2005)
531
Table 1. Reductive coupling of aryl halides
Ar Br, TDAE
PdCl (PhCN) (0.05 mmol)
2
2
TDAE (2 mmol)
2 Ar Br
1 (1 mmol)
Ar Ar
[Bdmim][BF ] (2 ml), 60 °C
4
2
Et O
2
Ar Ar
Et O
2
Time
/h
Yield 2
/%a
cat. Pd
Ionic Liquid
cat. Pd
Ionic Liquid
Entry
Aryl Bromide 1
Recycle
Use
1
2
3
4
5
6
7
8
9
10
11
12
13
4-MeOC6H4
4-Me2NC6H4
4-MeC6H4
4-EtCH(OH)C6H4
2-MeC6H4
4-MeOC(O)C6H4
4-BuOC(O)C6H4
4-EtC(O)C6H4
4-NCC6H4
3-NCC6H4
2-NCC6H4
1b
1d
1e
1f
1g
1a
1h
1i
1c
1j
1k
1l
5
10
8
7
24
2
3
3
3
3
68 (45)
58 (50)
80 (50)
53 (54)
<Reaction>
<Extraction>
Scheme 2. A totally closed system.
b
—
Br having both EDG and EWG. The reductive coupling of Ar–
Br having easily reduced functional groups, such as nitro and
formyl groups, can be performed successfully by using a small
excess amount of TDAE. Recycle-use of ionic liquid and Pd
catalyst was performed successfully when BdminTf2N was used
as a reaction solvent, which offers a totally closed system
(Scheme 2).
72 (70)
68 (75)
72 (75)
83 (83)
82
80
19 (43)
—c (80d)
6
3
3
4-HC(O)C6H4
4-O2NC6H4
1m
References and Notes
aIsolated yield. Yield in the parentheses were the values using
of 0.6 mmol (60 mol %) of TDAE. bAr–Br 1g was recovered.
c4-Amino-40-nitrobiphenyl (7) was obtained in 28% yield.
dNo 7 was detected.
1
H. Tanaka, Eco Ind., 7, 5 (2002); S. Kobayashi, J. Synth. Org.
Chem. Jpn., 59, 464 (2001); C.-J. Li, Green Chem., 1998, 234;
R. Breslow, Green Chem., 1998, 225; ‘‘Organic Synthesis in
Water,’’ ed. by P. A. Grieco, Blackie, London (1998).
M. Tokuda and N. Kurono, in ‘‘Yuki Denkai Gosei no
Shintenkai,’’ ed. by T. Fuchigami, CMC Shuppan, Tokyo
(2004), pp 190–202; H. Senboku and M. Tokuda, Fain
Kemikaru, 31, 50 (2002); H. Senboku and M. Tokuda, Kagaku
Sochi, 41, 55 (1999).
S. P. Luo, Z. B. Yiyuan, P. G. Wang, and J.-P. Cheng, Curr.
Org. Synth., 1, 405 (2004); P. Wasserscheid, in ‘‘Organic
Synthesis Highlights V,’’ ed. by H.-G. Schmalz and T. Wirth,
Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim (2003),
pp 105–117; T. Fuchigami and H. Ishii, Electrochemistry
(Tokyo), 70, 46 (2002); J. Dupont, R. F. de Souza, and
P. A. Z. Suarez, Chem. Rev., 102, 3667 (2002).
a) M. Kuroboshi, Y. Waki, and H. Tanaka, J. Org. Chem., 68,
3938 (2003). b) M. Kuroboshi, Y. Waki, and H. Tanaka,
Synlett, 2002, 637.
Recently, Alper reported a similar Pd/TDAE-promoted
coupling of aryl iodides in an IL (S. B. Park and H. Alper, Tet-
rahedron Lett., 45, 5515 (2004).) The scope of the reaction
was, however, strictly limited; thus, only aryl iodides could
undergo the reductive coupling.
In a previous reports, we found that Pd catalysts having
phosphine ligands, such as Pd(PPh3)4, PdCl2(PPh3)2, and
PdCl2(dppb) did not promote this Pd/TDAE-promoted
homo-coupling, and Pd2(dba)3 was less effective. See,
Refs. 4a and 4b.
a) R. R. Deshmukh, R. Rajagopal, and K. V. Srinivasan,
Chem. Commun., 2001, 1544. b) L. Xu, W. Chen, and J. Xiao,
Organometallics, 19, 1123 (2000).
In a previous reports, we also found that reactivity of Ar–Br
having EWG is higher than that of Ar–Br having EDG in
DMF. It is likely that EWG accelerates both Step 2 and Step 3
by reducing the electron density (redox potential) of Ar–Br (1)
and Ar–Pd–X (4).
After extractive work-up with Et2O, no significant increase
of the volume of the reaction medium (ionic liquid) was
observed, suggesting that by-products derived from TDAE
would be extracted with Et2O.
2
within 3 h. When the coupling of p-nitrobromobenzene (1m) was
carried out in BdmimBF4 at 60 ꢁC for 3 h, the reduction of the
nitro group occurred with TDAE and 4-amino-40-nitrobiphenyl
was formed in 28% yield, and no 2m was obtained. According
to the plausible mechanism, 50 mol % of TDAE is enough to
complete the reaction. When a small excess (60 mol %) of TDAE
was used, the desired 4,40-diformylbiphenyl (2k) and 4,40-dini-
trobiphenyl (2m) were obtained in 43 and 80% yield, respective-
ly (Entries 12, 13).
3
The recycle use of ionic liquid containing the Pd catalysts
was studied using 4-cyanobromobenzene (1c) (Table 2).
4
5
Table 2. Recycle use of ionic liquids and Pd catalyst
Cyclea
Ionic liquid
Yield 2c/%b
Recov. 1c/%b
1st
2nd
3rd
BdminTf2N
BdminTf2N
BdminTf2N
93
93
86
—
4
7
1st
2nd
3rd
BdmimBF4
BdmimBF4
BdmimBF4
83
4
3
—
71
79
6
a1c (1 mmol), TDAE (2 mmol), ionic liquid (2 mL), 60 ꢁC, 3 h.
Pd catalyst (0.05 mmol) was added for the 1st cycle. No Pd
catalyst was added in the 2nd and 3rd cycles. Isolated yield.
b
7
8
Biaryl 2c was obtained in more than 80% yield even in the
third cycle when BdminTf2N was used.9 On the other hand,
when the recovered BdmimBF4 was reused at the second cycle,
the biaryl 2c was obtained in only 4% yield. It is not clear yet,
but a small amount of acid, which was generated from decompo-
ꢂ
sition of BF4 during the reaction and/or work-up, would pre-
vent the reductive coupling reaction.
9
In conclusion, Pd/TDAE-promoted reductive coupling of
Ar–Br can be performed in ionic liquids such as BdmimBF4
and BdminTf2N. The reaction proceeded effectively with Ar–
Published on the web (Advance View) March 5, 2005; DOI 10.1246/cl.2005.530