Conversion of tributylstannylferrocene to a variety of heteroaryl ferrocenes

Article abstract of DOI:10.1016/S0022-328X(99)00733-0

Tributylstannylferrocene (Fc-SnBu₃) was converted to a variety of heteroaryl ferrocenes, such as 2-thiophenyl, 3-thiophenyl, 3-pyridyl, 3-quinolyl, 4-oxazolyl and 4-isoxazolyl ferrocene, by using Pd-catalyzed reactions. The Stille-coupling catalyst (PdCl₂-PPh₃) promotes the reaction between Fc-SnBu₃ and electron-deficient heterocyclic bromides, while a modified catalyst (Pd-Ph₃P-CuO) proves to be the choice for the coupling of Fc-SnBu₃ with electron-rich heterocyclic bromides.

Full text of DOI:10.1016/S0022-328X(99)00733-0

www.elsevier.nl/locate/jorganchem
Journal of Organometallic Chemistry 598 (2000) 348–352
Conversion of tributylstannylferrocene to a variety of heteroaryl
ferrocenes
Chao-Min Liu, Bao-Hua Chen, Wan-Yi Liu, Xiao-Li Wu, Yong-Xiang Ma *
National Laboratory of Applied Organic Chemistry, Lanzhou Uni6ersity, Lanzhou 730000, PR China
Received 4 August 1999; received in revised form 4 November 1999; accepted 9 November 1999
Abstract
Tributylstannylferrocene (FcꢀSnBu3) was converted to a variety of heteroaryl ferrocenes, such as 2-thiophenyl, 3-thiophenyl,
3-pyridyl, 3-quinolyl, 4-oxazolyl and 4-isoxazolyl ferrocene, by using Pd-catalyzed reactions. The Stille-coupling catalyst
(PdCl2–PPh3) promotes the reaction between FcꢀSnBu3 and electron-deficient heterocyclic bromides, while a modified catalyst
(Pd–Ph3P–CuO) proves to be the choice for the coupling of FcꢀSnBu3 with electron-rich heterocyclic bromides. © 2000 Elsevier
Science S.A. All rights reserved.
Keywords: Tributylstannylferrocene; Heterocyclic bromides; Stille coupling; Heteroarylferrocene
Tributylstannylferrocene (FcꢀSnBu3) was prepared
decades ago and used as an additive of lubricating oil
[10]. Recently, Kagan and co-workers reported proce-
dures for efficient preparation of tributylstannylfer-
rocene [11,12]. Although the reported methods gave
some undesired bis-substituted ferrocenes, the desired
mono derivative was produced in good yield (70%).
Our laboratory described an alternative protocol [13],
which features easy reaction conditions and less con-
tamination of bis-stannyl ferrocene. Herein, we report
the use of tributylstannylferrocene as a key intermedi-
ate for synthesizing a variety of heteroaryl ferrocenes
via palladium-promoted coupling reactions.
1. Introduction
Procedures have been reported for the synthesis of
ferrocene-containing heterocyclic rings [1–6]. These fer-
rocene derivatives are useful materials for their applica-
tions in electrochemistry [7,8], biochemistry and
materials science [9]. Ring cyclization reactions have
been useful methods for preparing ferrocene-attached
heterocycles [1–3], since the cyclization chemistry can
focus specifically on heterocyclic ring formations. Alter-
natively, procedures have been developed for the intro-
duction of heteroaryl groups into Cp rings of ferrocene
[3–6], giving 1,1%-bis(2-heteroaryl) ferrocene structures.
We are interested in developing methods for efficient
synthesis of a variety of heterocyclic ferrocene com-
pounds, in which one heteroaryl ring is bonded to
ferrocene. Our methodology allows for the construction
of compounds with multi-functional groups, including
amide, amine, ester, halogen, ketone and nitro moieties.
To avoid the tedious de novo synthesis of individual
functionalized compounds, it is desirable to develop a
protocol that would promote the coupling of bromo-
substituted heterocyclic rings to a common intermediate
such as tributylstannylferrocene (FcꢀSnBu3).
2. Results and discussion
The palladium-catalyzed reactions were initially in-
vestigated by the coupling of bromo-substitued quino-
line derivatives 1a–e with tributylstannylferrocene (2)
(Scheme 1). The use of a PdCl2(PPh3)2 complex pro-
moted the desired couplings by heating the mixture of
starting materials at 100–120°C in DMF. It appears
that the benzene ring of quinoline can be substituted
with either electron-donating or -withdrawing groups.
The desired compounds 3a–e were generally obtained
in good yields.
* Corresponding author. Fax: +86-931-8858528.
E-mail address: mayx@lzu.edu.cn (Y.-X. Ma)
0022-328X/00/$ - see front matter © 2000 Elsevier Science S.A. All rights reserved.
PII: S0022-328X(99)00733-0

C.-M. Liu et al. / Journal of Organometallic Chemistry 598 (2000) 348–352
349
Scheme 1.
mixtures for several hours to give the desired products
in high yields. The co-catalyst system (Pd–PPh3–CuO)
offers an excellent option for electron-rich heterocyclic
derivatives. Both systems use one-step procedures to
synthesize efficiently a variety of functionalized het-
eroarylferrocenes, which are otherwise difficult to
obtain.
Mono heterocyclic rings were then used to probe the
influence of ring electronic properties on the palladium-
catalyzed carbonꢀcarbon bond formation (Table 1).
The complex of palladium chloride and triphenylphos-
phine promoted the coupling reactions between tri-
butylstannylferrocene and a variety of functionalized
pyridines (entries 9–12 and 14) and thiophenes (entries
17–20, 23–25). It was interesting to note that
PdCl2(PPh3)2 did not catalyze the coupling reactions of
FcꢀSnBu3 with simple pyridines such as 2-bromopyr-
idine (entry 6). Similar results were also observed for
3-bromopyridine (entry 9), several amino pyridines (en-
tries 15–16) and 3-thiophene (entry 21). Results were
not improved by using other related catalysts:
PdClBz(PPh3)2 or PdCl2(dppf) (not shown). We at-
tempted to change the electronic property of 2-amino-
5-bromopyridine by forming its hydrochloride salt, but
the coupling of the salt with FcꢀSnBu3 gave fruitless
results (trace to 25% yields, not shown). It can be
generalized that PdCl2(PPh3)2 promoted the desired
couplings of FcSnBu3 with only electron-deficient
mono-heterocyclic systems.
For electron-rich heterocyclic bromides, we investi-
gated the use of co-catalyst with the hope of generating
a reactive palladium species or increasing the reactivity
of heterocyclic rings by chelation. It was found that
addition of CuO significantly improved the yield of
compounds 3f (entries 6–7). Similar results were ob-
tained from 3-bromopyridine, 2-amino-3,5-dibromopyr-
idine and 3-bromothiophene (entries 8, 13 and 22).
Although the Pd(PPh3)4ꢀCuO system had no catalytic
effect on two pyridine derivatives (entries 13–14), it
gave satisfactory yields for isoxazole and oxazole (en-
tries 26–27). It was also observed that the Pd–PPh3–
CuO catalytic system gave the desired products
(68–95% yield) in a relatively short period of time
(about 1–4 h).
3. Experimental
Infrared (IR) spectra were recorded in KBr on a
1
Nicolet 179SX FT-IR spectrometer. H-NMR spectra
were recorded on a FC-80A spectrometer using CDCl3
as a solvent. Mass spectra were obtained on a VG
ZBA-HS or HP5989A mass spectrometer.
3.1. Coupling procedure using PdCl2(PPh3)2
A mixture of bromosubstituted heteroarene (0.5
mmol), PdCl2(PPh3)2 (0.025 mmol) and FcꢀSnBu3 (0.55
mmol) in dry DMF (4 ml) was stirred at 120–130°C for
the time given in Table 1. After the mixture was cooled
to room temperature, water (8 ml) was added and the
resulting solution was extracted with ether or
dichloromethane. The organic layer was sequentially
washed with saturated KF solution, water, and dried
over MgSO4. Evaporation of solvents gave a residue
that was purified by chromatography on a silica gel
column (eluant: petroleum–acetone in a ratio that was
determined by the TLC studies of each product).
3.2. Coupling procedure using Pd(PPh3)4ꢀCuO
A mixture of bromosubstituted heteroarene (0.5
mmol), Pd(PPh3)4 (0.025 mmol) and CuO (0.5 mmol) in
dry DMF (4 ml) was heated to 130°C under argon for
30 min. Tributylstannylferrocene (0.55 mmol) was then
added in one portion at 100°C, and heating was contin-
ued at 120–130°C for the time given in Table 1. The
aforementioned work-up procedure was used for ob-
taining the desired product.
Tributylstannylferrocene was shown to be a suitable
starting material for the synthesis of mono-substituted
heteroarylferrocene compounds via Pd-catalytic cou-
pling reactions. The standard complex of PdCl2 and
triphenylphosphine was the first choice, since the reac-
tions can be simply carried out by heating the reaction

350
C.-M. Liu et al. / Journal of Organometallic Chemistry 598 (2000) 348–352
Table 1
Coupling results between FcꢀSnBu3 and various heterocyclic bromides

C.-M. Liu et al. / Journal of Organometallic Chemistry 598 (2000) 348–352
351
1
3a was obtained as deep red solid, d.p. 155°C H-
NMR: l 2.6 (s, 3H), 4.05 (s, 5H), 4.46 (m, 2H), 4.77 (m,
2H), 7.73 (s, 1H), 7.8 (s, 1H), 8.01 (s, 1H), 9.13 (s, 1H);
IR: 1065, 1503, 1101, 999, 486 cm−1; FAB MS: m/z
372 (M+, 18%).
2H); IR: 3037, 1588, 1496, 1102, 1009, 485 cm−1; FAB
MS m/z 341 (M+, 50%), 343 (M+, 48%).
3o: orange red solid, m.p. 90–92°C (reported 116.5–
117.5°C [6]); H-NMR: l 7.28–6.87 (m, 3H), 4.79 (m,
1
2H), 4.43 (m, 2H), 4.27 (s, 5H); IR: 3084, 1597, 1540,
1456, 1104, 1000, 507 cm−1; FAB MS m/z 268 (M+,
72.5%).
1
3b was obtained as deep red solid, d.p. 145°C H-
NMR: l 2.8 (s, 3H), 4.0 (s, 5H), 4.4 (m, 2H), 4.74 (m,
2H), 8.07 (s, 1H), 8.17 (s, 1H), 8.47 (s, 1H), 9.13 (s,
1H); IR: 1603, 1478, 1092, 1000, 490 cm−1; FAB MS:
m/z 372 (M+, 28%).
1
3p: purple solid, m.p. 120–122°C; H-NMR: l 7.79
(d, J=4.2 Hz, 1H), 6.94 (d, J=4.2, 1H), 4.70 (m, 2H),
4.50 (m, 2H), 4.16 (s, 5H); IR: 3048, 1535, 1485, 1462,
1103, 1001, 489 cm−1; FAB MS m/z 313 (M+, 57.5%).
3q: deep red solid, m.p. 151–154°C (reported 148–
3c: deep red solid, d.p. 150°C 1H-NMR: l 3.9 (s,
3H), 4.0 (s, 5H), 4.4 (m, 2H), 4.71 (m, 2H), 7.15 (s, 1H),
7.55 (s, 1H), 7.94 (s, 1H), 8.9 (s, 1H); IR: 1625, 1496,
1252, 1096, 1009, 481 cm−1; FAB MS m/z 388 (M+,
6%).
1
151°C [14]); H-NMR: l 7.53 (d, J=3.9, 1H), 7.02 (d,
J=3.9, 1H), 4.67 (m, 2H), 4.40 (m, 2H), 4.12 (s, 5H),
2.55 (s, 3H); IR: 3082, 2949, 1648, 1100, 1022, 491
cm−1; FAB MS m/z 310 (M+, 100%).
1
3d: deep red solid, d.p. 160°C H-NMR: l 3.95 (s,
3r: deep red solid, m.p. 125–128°C; 1H-NMR: l
7.94–7.55 (m, 5H), 7.47 (d, J=3.9, 1H), 7.04 (d, J=
3.9, 1H), 4.72 (m, 2H), 4.44 (m, 2H), 4.15 (s, 5H); IR:
3084, 3025, 1682, 1575, 1475, 1446, 1106, 999, 506
cm−1; FAB MS m/z 372 (M+, 2%), 371 (8.3%).
5H), 4.05 (s, 3H), 4.37 (m, 2H), 4.7 (m, 2H), 7.61 (s,
1H), 8.05 (s, 1H), 8.20 (s, 1H), 9.07 (s, 1H); IR: 1611,
1489, 1258, 1085, 996, 499 cm−1; FAB MS m/z 388
(M+, 18%).
1
3e: deep red solid, d.p. 150°C H-NMR: l 3.98 (s,
5H), 4.4 (m, 2H), 5.7 (m, 2H), 7.8 (s, 2H), 7.9 (s, 1H),
9.05 (s, 1H); IR: 1603, 1489, 1092, 997 cm−1; FAB MS
m/z 392 (M+, 9.5%).
1
3s: orange solid, m.p. 100–102°C; H-NMR: l 7.6–
7.15 (m, 3H), 4.67 (m, 1H), 4.57 (m, 1H), 4.31 (m, 2H),
4.08 (s, 5H); IR: 3092, 1599, 1549, 1514, 1450, 1101,
999 cm−1; FAB MS m/z 268 (M+, 90.5%).
3f: orange solid, m.p. 93–94°C (reported 91–92°C
1
[5]); H-NMR: l 8.52 (d, J=4.88 Hz, 1H), 7.72–7.38
1
3t: purple solid, m.p. 92–94°C; H-NMR: l 8.70 (s,
(m, 2H), 7.09 (m, 1H), 4.97 (m, 2H), 4.44 (m, 2H), 4.09
1H), 8.48 (d, J=7.32 Hz, 1H), 8.22 (d, J=7.78 Hz,
1H), 7.73 (m, 1H), 7.47 (d, J=3.99 Hz, 1H), 7.09 (d,
J=3.99 Hz, 1H), 4.57 (m, 2H), 4.33 (m, 2H), 4.10 (s,
5H); IR: 3091, 1628, 1529, 1481, 1091, 998 cm−1; FAB
MS m/z 417 (M+, 67.3%).
(s, 5H); FAB MS m/z 263 (M+, 100%).
3g: orange solid, m.p. 52–54°C (reported 57–59°C
1
[5]); H-NMR: l 4.07 (s, 5H), 4.38 (m, 2H), 4.68 (m,
2H), 7.18 (m, 1H), 7.73 (m, 1H), 8.44 (m, 1H), 8.75 (s,
1H); IR: 3060, 1591, 1496, 1100, 1000, 496 cm−1; FAB
MS m/z 263 (M+, 100%).
3u: deep red liquid; 1H-NMR: l 7.67 (d, J=4.2, 1H),
7.16 (d, J=4.2, 1H), 4.712 (m, 2H), 4.43 (m, 2H), 4.21
(s, 5H), 2.38 (s, 3H); IR: 3093, 1649, 1528, 1459, 1106,
1002 cm−1; FAB MS m/z 310 (M+, 10%), 309 (61%).
1
3h: purple solid, m.p. 236–238°C; H-NMR: l 4.11
(s, 5H), 4.56 (m, 2H), 4.81 (m, 2H), 7.98 (dd, J=8.29.
2.07 Hz, 1H), 8.19 (d, J=8.29 Hz, 1H), 8.68 (d,
J=2.07 Hz, 1H); IR: 3049, 1576, 1523, 1494, 1107,
1021, 501 cm−1; FAB MS m/z 308 (M+, 100%).
3i: bright brownish yellow solid, m.p. 171–173°C;
1H-NMR: l 2.23 (s, 3H), 4.07 (s, 5H), 4.37 (m, 2H),
4.64 (m, 2H), 7.79 (dd, J=8.161, 76 Hz, 1H), 8.17 (d,
J=8.61 Hz, 1H), 8.38 (d, J=1.76 Hz, 1H), 8.92 (NH);
1
3v: deep red solid, m.p. 37–40°C; H-NMR: l 7.73–
7.21 (m, 7H), 4.50–4.07 (m, 9H); IR: 3092, 1630, 1596,
1534, 1447, 1108, 1000, 500 cm−1; FAB MS m/z 372
(M+, 77.6%).
1
3w: red solid, m.p. 124–126°C; H-NMR: l 7.35–
7.66 (m, 5H), 4.66 (q, J=7.2, 2H), 4.54 (m, 2H), 4.31
(m, 2H), 4.06 (s, 5H), 1.54 (t, J=7.2, 3H); IR: 3088,
1735, 1614, 1475, 1440, 1101, 1007, 492 cm−1; FAB
MS m/z 401 (M+, 100%)
IR: 3238, 3088, 1663, 1579, 1442, 1102, 999, 489 cm−1
;
FAB MS m/z 320 (M+, 100%).
1
3j: purple solid, m.p. 198–200°C; H-NMR: l 4.10
(s, 5H), 4.38 (m, 2H), 4.63 (m, 2H), 8.40 (d, J=2.42
Hz, 1H), 8.53 (d, J=2.42 Hz, 1H); IR: 3467, 3280,
1
3x: red solid, m.p. 125–127°C; H-NMR: l 8.09–
8.28 (m, 2H), 7.80–7.93 (m, 2H), 7.30–7.65 (m, 6H),
4.75 (m, 2H), 4.37 (m, 2H), 4.25 (s, 5H); IR: 3055, 1551,
1453, 1449, 1109, 1001, 487 cm−1; FAB MS m/z 405
(M+, 100%).
3055, 1641, 1564, 1522, 1440, 1107, 1000, 471 cm−1
;
FAB MS m/z 323 (M+, 100%);
1
3k: reddish orange solid, m.p. 123–124°C; H-NMR:
l 4.22 (s, 5H), 4.46 (m, 2H), 4.57 (m, 2H), 5.32 (NH2),
7.61 (d, J=2.33 Hz, 1H), 8.03 (d, J=2.33 Hz, 1H); IR:
3446, 3288, 1619, 1560, 1448, 1105, 1000, 493 cm−1
;
Acknowledgements
FAB MS m/z 356 (M+, 99.43%), 358 (M+, 100%).
1
This research has been supported by Middle-Young
Science Foundation of Gansu Province no. ZQ-97-002.
3l: orange solid, m.p. 46–49°C; H-NMR: l 4.09 (s,
5H), 4.43 (m, 2H), 4.68 (m, 2H), 8.04 (m, 1H), 8.77 (m,
.

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C.-M. Liu et al. / Journal of Organometallic Chemistry 598 (2000) 348–352
(d) J.G.P. Delis, P.W.N.M. Van Leeuwen, K. Vrieze, N. Veldman,
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