Synthesis of 1′,1?-bis(heterocyclyl)biferrocene compounds

Article abstract of DOI:10.1016/S0022-328X(01)00895-6

A new method for preparing 1′,1?-disubstituted heterocyclylbiferrocene derivatives via stepwise Stille coupling reaction of 1,1′-bis(tributylstannyl)ferrocene with heterocyclic bromides and subsequent Cu-catalyzed homocoupling reaction is established.

Full text of DOI:10.1016/S0022-328X(01)00895-6

Journal of Organometallic Chemistry 637–639 (2001) 723–726
www.elsevier.com/locate/jorganchem
Note
Synthesis of 1%,1§-bis(heterocyclyl)biferrocene compounds
Chao-Min Liu a, Yong-min Liang a, Xiao-li Wu a, Wei-min Liu b, Yong-xiang Ma a,*
a National Laboratory of Applied Organic Chemistry, Lanzhou Uni6ersity, Lanzhou 730000, People’s Republic of China
b Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences,
Lanzhou 730000, People’s Republic of China
Received 12 November 2000; received in revised form 20 February 2001; accepted 21 February 2001
Abstract
A new method for preparing 1%,1§-disubstituted heterocyclylbiferrocene derivatives via stepwise Stille coupling reaction of
1,1%-bis(tributylstannyl)ferrocene with heterocyclic bromides and subsequent Cu-catalyzed homocoupling reaction is established.
© 2001 Elsevier Science B.V. All rights reserved.
Keywords: Ferrocene; Stille coupling; Homocoupling; Heterocyclylbiferrocene
lithium–bromine exchange and finally by an elec-
trophilic attack to give the desired products [18] as
1. Introduction
shown in Scheme 1. The disadvantages of these proce-
The applications of heterocyclyl ferrocene derivatives
dures are: (i) dibromoferrocene is tedious to prepare;
in electrochemistry, materials science and biochemistry
(ii) lithium–bromine exchange needs drastic condition;
are well known [1–3]. In these areas of study bifer-
and (iii) active lithioferrocene intermediate cannot tol-
rocene-type compounds are perhaps attractive candi-
erate many active groups such as amino, hydroxy and
dates [4–18]. Dong and co-workers [10–18], in recent
the like, which are bonded on electrophilic reagents. In
years, have reported a series of studies on the electron-
addition, owing to the methodological limitation in
transfer rate in mixed-valance biferrocenium salts and
their preparation, substituents on 1% and 1§ position
established two effective methods for the synthesis of
were mostly simple groups.
1%,1§-disubstituted biferrocene derivatives [17,18]. One
In continuation of our studies [19–21] on the synthe-
is selective lithium–bromine exchange of 1,1%-dibromo-
sis of ferrocenyl heterocyclic derivatives, our interest is
ferrocene, followed by an electrophilic attack and
finally homocoupling under active Cu [17]. Another is
direct coupling of 1,1%-dibromoferrocene, using CuCN
and oxygen as the coupling reagents, subsequently
in developing different methods for the synthesis of
varied heterocyclyl ferrocene compounds using 1,1%-
bis(tributylstannyl)ferrocene as the starting material. In
present literature, no biferrocene compounds bearing
heterocyclyl directly bonded on 1% and 1§ position are
reported so far. This paper is concerned with the prepa-
ration of this type of compounds.
2. Results and discussion
Scheme 1.
1,1%-Bis(tributylstannyl)ferrocene (1) was obtained
following the literature procedure [22,23]. This was
found not only to undergo selective transmetalation
* Corresponding author. Fax: +86-931-861-1688.
E-mail address: mayx@lzu.edu.cn (Y.-x. Ma).
0022-328X/01/$ - see front matter © 2001 Elsevier Science B.V. All rights reserved.
PII: S0022-328X(01)00895-6

724
C.-M. Liu et al. / Journal of Organometallic Chemistry 637–639 (2001) 723–726
Compared with Dong’s procedure, our method has
several advantages: (i) basic substrate, 1,1%-bis(tributyl-
stannyl)ferrocene, is easily obtained under ordinary lab-
oratory conditions in high yield (80%) or can be
directly purchased; (ii) reaction condition is mild and
simple; and (iii) it can tolerate all kinds of active
groups.
1,1%-Bis(tributylstannyl)ferrocene was shown to be a
good starting material for the synthesis of various
functionalized 1%,1§-bis(heterocyclyl)ferrocene com-
pounds via two-step coupling, which are otherwise
difficult to obtain.
Scheme 2. (i) Het-Br 150% of 1 and 0.5% of PdCl2(PPh3)2 in DMF at
100–200 °C heated for 1–1.5 h. (ii)
2 and stoichiometrical
CuSO4·3H2O in THF stirred at r.t. for 1–8 h.
Table 1
Results of stepwise Stille coupling and subsequent homocoupling
Entry Time (h)
Products
Yield (%)
Melting point (°C)
Stille coupling
3. Experimental
1
2
3
4
5
1
2a
2b
2c
2d
2e
70
73
71
75
65
1.5
1.5
1
3.1. General
1
Melting points were determined on a Thomas
Hoover capillary melting point apparatus and were
uncorrected. 1H-NMR spectra were measured on a
FC-80A spectrometer in CDCl3 with Me4Si as the
internal standard. Mass spectra (MS) were taken on
Finnigan TQ70 or HP-5988 AG CMS mass spectrome-
ter. IR spectra were recorded on a Nicolet 179SX
FT-IR spectrometer as KBr pellets.
Homocoupling
6
10
3a
3b
3c
3d
3e
3f
90
85
88
60
45
96
158–159
166 (dec.)
196 (dec.)
128–130
82–84
7
8
8
8
9
10
10
11
13
40 min
283 (dec.)
/c\\3fca=‘‘D’’\\96ca=‘‘D’’\\283 (dec.)
reaction but also a smooth stepwise Stille across-cou-
pling reaction, and has been judged to be one of the
excellent starting material for the preparation of 1,1%-
disubstituted ferrocene derivatives via these reactions
[21–23]. Various 1-heterocyclyl-1%-tributylstannylfer-
rocenes (2) could be easily obtained via the selective
monosubsituted Stille coupling and the intermediates
can subsequently be used as precursors for the prepara-
tion of title compounds (3) as indicated in Scheme 2.
Treatment of an excess of 1 with appropriate hetero-
cyclic bromides under PdCl2(PPh3)2 in dry DMF at
100–120 °C gave 2 in satisfactory yields (entries 1–5)
as a deep red oil along with some monosubstituted
heterocyclylferrocene as by-products.
Homocoupling of organostannanes have been recog-
nized as one of the useful synthetic methods to form
symmetrical biaryl, 1,3-dienes and 1,3-diynes [24–26].
Copper-promoted homocoupling was initially investi-
gated by the coupling of tributylstannylferrocene itself
(entry 11). The use of Cu2+ promoted the desired
homocoupling by stirring the mixture of tributylstan-
3.2. 1-Tributylstannyl-1%-heteroarylferrocene (2):
general procedure
To the mixture of 1,1%-bis(tributylstannyl)ferrocene
(1) (2.05 g, 2.68 mmol) and PdCl2(PPh3)2 (0.06 g, 0.09
mmol) in dry DMF (6 ml), corresponding bromides
(1.78 mmol) were added with stirring. The mixture was
heated on an oil bath at 100–120 °C for periods of
time given in Table 1. After cooling, saturated ammo-
nium chloride solution was added to the mixture. Then
the mixture was extracted with petroleum ether (30–60)
or diethyl ether, washed with saturated KF solution
and water. The organic layer was dried on MgSO4,
filtered, and concentrated in vacuo. ‘Flash’ chromatog-
raphy of the crude product was done on neutral or
alkaline Al2O3. The first band eluted with petroleum
ether (30–60) was 1 together with some tributylstannyl-
ferrocene, then a little destannylation product, fer-
rocene, was obtained. Continued elution with
petroleum ether (30–60)–Et2O (10:1) gave elutes which
yielded the desired product (2). The last band was
monosbustituted by-product, heterocyclylferrocene.
1- Tributylstannyl - 1% - (2 - nitro - pyrid - 5 - yl)ferrocene
nylferrocene
and
stoichiometrical
amount
of
CuSO4·3H2O in THF at room temperature. The desired
product, biferrocene, was obtained quickly in almost
quantity yield. Other compounds (3) were obtained by
the same procedure in satisfactory yields (entries 6–10),
along with a little destannylation product, monosubsti-
tuted heterocyclylferrocene, as by-product. The results
are summarized in Table 1.
1
(2a): deep-red oil, 70%. H-NMR (CDCl3, l ppm): 8.66
(d, J=2.17 Hz, 1H), 8.20 (d, J=8.22 Hz, 1H), 7.99
(dd, J=2.17, 8.22 Hz, 1H), 4.75 (m, 2H), 4.49 (m, 2H),
4.21 (m, 2H), 3.96 (m, 2H), 1.78–0.90 (m, 27H). IR
(cm−1): 3080, 2958, 2927, 2867, 1577, 1533, 1462, 1089,

C.-M. Liu et al. / Journal of Organometallic Chemistry 637–639 (2001) 723–726
725
1024. Anal. Found: C, 54.64; H, 6.67; N, 4.38. Calc. for
C27H38FeN2O2Sn: C, 54.36; H, 6.37; N, 4.69%.
1-Tributylstannyl-1%-(8-methyl-6-nitro-quino-5-yl)-
1%,1§-Bis(8-methyl-6-nitroquino-3-yl)diferrocene (3b):
deep-red solid, 85%, m.p. 166 °C (dec.). 1H-NMR
(CDCl3, l ppm): 8.26 (d, J=1.84 Hz, 2H), 8.58 (d,
J=2.19 Hz, 2H), 8.25 (m, 4H), 4.87 (s, 4H), 4.51 (s,
4H), 4.32 (s, 4H), 4.10 (s, 4H), 2.90 (s, 6H). IR (cm−1):
3113, 1530, 1090, 1028, 475. MS (m/z): 742 ([M], 13),
741 (3).
1
ferrocene (2b): deep-red oil, 85%. H-NMR (CDCl3, l
ppm): 9.28 (d, J=2.16 Hz, 1H), 8.58 (d, J=2.34, 1H),
8.29 (d, J=2.16 Hz, 1H), 8.19 (d, J=2.34 Hz, 1H),
4.79 (m, 2H), 4.45 (m, 2H), 4.24 (m, 2H), 3.96 (m, 2H),
2.99 (s, 3H), 1.86–0.82 (m, 27H). IR (cm−1): 3084,
2958, 2927, 2865, 1612, 1528, 1093, 1026, 435. Anal.
Found: C, 60.89; H, 6.23; N, 3.96. Calc. for
C32H42FeN2O2Sn: C, 60.57; H, 6.00; N, 4.00%.
1%,1§-Bis(6-methyl-8-nitroquino-3-yl)diferrocene (3c):
deep-red solid, 85%, m.p. 196 °C (dec.). 1H-NMR
(CDCl3, l ppm): 9.21 (bs, 2H), 8.09 (bs, 2H), 7.86 (bs,
2H), 7.78 (bs, 2H), 4.83 (s, 4H), 4.51 (s, 4H), 4.34 (s,
4H), 4.12 (s, 4H), 2.60(s, 6H). IR (cm−1): 3085, 1561,
1527, 1090, 1025, 497. MS (m/z): 742 ([M], 8).
1%,1§-Bis(2-benzoylthien-5-yl)diferrocene (3d): deep-
1-Tributylstannyl-1%-(6-methyl-8-nitro-quino-5-yl)-
1
ferrocene (2c): deep-red oil, 83%. H-NMR (CDCl3, l
ppm): 9.18 (d, J=2.08 Hz, 1H), 8.86 (d, J=1.89 Hz,
1H), 8.03 (d, J=2.08 Hz, 1H), 7.89 (d, J=1.89 Hz,
1H), 4.73 (m, 2H), 4.42 (m, 2H), 4.21 (m, 2H), 3.95 (m,
2H), 2.60 (s, 3H), 1.82–0.80 (m, 27H). IR (cm−1):
3043, 2958, 2927, 2865, 1532, 1461, 1085, 1027. Anal.
Found: C, 60.83; H, 6.18; N, 3.98. Calc. for
C32H42FeN2O2Sn: C, 60.57; H, 6.00; N, 4.00%.
1-(2-Benzoylthien-5-yl)-1%-(tributylstannyl)ferrocene
(2d): deep-red oil, 75%. 1H-NMR (CDCl3, l ppm):
7.92–7.41 (m, 6H), 7.03 (d, J=3.92 Hz, 2H), 4.65 (m,
2H), 4.35 (m, 2H), 4.29 (m, 2H), 3.97 (m, 2H), 1.8–0.9
(m, 27H). IR (cm−1): 3084, 2957, 2925, 2863, 1634,
1597, 1514, 1454, 1076, 1025, 1000, 500, 412. Anal.
Found: C, 60.10; H, 6.38. Calc. for C33H42FeOSSn: C,
59.95; H: 6.36%.
1
red solid, 60%, m.p. 128–130 °C. H-NMR (CDCl3, l
ppm): 7.90–7.45 (m, 10H), 7.34 (d, J=3.93 Hz, 2H),
6.77 (d, J=3.93 Hz, 2H), 4.45 (bs, 4H), 4.24 (bs, 4H),
4.11 (bs, 10H). IR (cm−1): 3064, 1738, 1615, 1465,
1089, 1023, 483. MS (m/z): 742 ([M], 20.96), 105
(62.61), 77 (64.62), 56 (19.77).
1%,1§-Bis(2-acetylthien-5-yl)diferrocene (3e): deep-red
1
solid, 45%, m.p. 82–84 °C. H-NMR (CDCl3, l ppm):
7.39 (d, J=3.80 Hz, 2H), 6.71 (d, J=3.80 Hz, 2H),
4.41 (s, 4H), 4.20 (s, 4H), 4.08 (bs, 8H), 2.51 (s, 6H). IR
(cm−1): 3085, 1698, 1649, 1577, 1458, 1080, 1028, 473.
MS (m/z): 618 ([M], 16.85), 57 (54), 43 (95.06), 41
(100).
Biferrocene (3f): red solid, 96%, m.p. 238 °C (dec.).
1H-NMR (CDCl3, l ppm): 4.36 (bs, 4H), 4.18 (bs, 4H),
4.01 (s, 10H).
1 - Tributylstannyl - 1% - (2 - acetylthien - 5 - yl)ferrocene
1
(2e): deep-red oil, 65%. H-NMR (CDCl3, l ppm): 7.53
(d, J=3.74 Hz, 1H), 7.50 (d, J=3.74 Hz, 1H), 4.61 (m,
2H), 4.34 (m, 2H), 4.25 (m, 2H), 3.96 (m, 2H), 2.54 (s,
3H), 1.6–0.9 (m, 27H). IR (cm−1): 3088, 2958, 2926,
2863, 1653, 1480, 1418, 1080, 1027. Anal. Found: C,
56.26; H, 6.71. Calc. for C28H40FeOSSn: C, 56.14; H,
6.68.
References
[1] A. Benito, R. Martinez-Manez, J. Paya, J. Sots, M.J.L. Tendero,
E. Sinn, J. Organomet. Chem. 503 (1995) 259.
[2] I.R. Butler, J.-L. Roustan, Can. J. Chem. 69 (1991) 1117.
[3] M.-G.A. Shvekhgeimer, Uspekhi Khim. 65 (1996) 43.
[4] S. Nakashima, M. Katada, I. Motoyma, H. Sano, Bull. Chem.
Soc. Jpn. 59 (1986) 2923.
3.3. 1%,1§-Bis(heteroaryl)diferrocene (3): general
procedure for the homocoupling of 2
[5] M.J. Cohn, T.-Y. Dong, D.N. Hendrickson, S.J. Geib, A.L.
Rheingold, J. Chem. Soc. Chem. Commun. (1985) 1059.
[6] S. Iijima, R. Saida, I. Motoyma, H. Sano, Bull. Chem. Soc. Jpn.
54 (1981) 1375.
[7] S. Nakashima, M. Katada, I. Motoyma, H. Sano, Bull Chem.
Soc. Jpn. 60 (1987) 2253.
[8] M. Konno, S.-A. Hyodo, S.-I. Iijima, Bull. Chem. Soc. Jpn. 55
(1982) 2327.
[9] R.J. Webb, S.J. Geib, D.L. Staley, A.L. Rheingold, D.N. Hen-
driekson, J. Am. Chem. Soc. 112 (1990) 5031.
[10] T.-Y. Dong, C.-C. Schei, T.-L. Hsu, S.-L. Lee, S.-J. Li, Inorg.
Chem. 31 (1991) 2457.
[11] T.-Y. Dong, C.-K. Chang, C.-H. Huang, Y.-S. Wen, S.-L. Lee,
J.-A. Chen, W.-Y. Yeh, A. Yeh, J. Chem. Soc. Chem. Commun.
(1992) 526.
[12] T.-Y. Dong, C.-H. Huang, C.-K. Kang, Y.-S. Wen, S.-L. Lee,
J.-A. Chen, W.-Y. Yeh, A. Yeh, J. Am. Chem. Soc. 115 (1993)
6357.
Stoichimetrical amount of CuSO4·3H2O was added in
a single portion to 2 (0.25 mmol) in THF (5 ml). The
mixture was stirred at ambient temperature for the
time-period given in Table 1. The reaction mixture was
diluted with Et2O (3d–3f) or CH2Cl2 (3a–3c), washed
with aqueous ammonia (5% soln.), water, brine, and
then dried over MgSO4 and concentrated in vacuo. The
crude product was subjected to column chromatogra-
phy on silica gel (petroleum ether–methanol) and af-
forded corresponding homocoupling biferrocene
derivatives (3) in 45–96% yield.
1%,1§-Bis(2-nitropyrid-5-yl)diferrocene (3a): deep-red
crystal, 90%, m.p. 158–159 °C. 1H-NMR (CDCl3, l
ppm): 8.74 (s, 2H), 8.17 (d, J=8.40 Hz, 2H), 8.08 (d,
J=8.40 Hz, 2H), 4.85 (m, 4H), 4.65 (m, 4H), 4.29 (m,
4H), 4.32 (s, 4H), 4.05 (s, 4H). IR (cm−1): 3085, 1577,
1523, 1107, 1081, 1019, 476. MS; m/z): 614 ([M], 12).
[13] T.-Y. Dong, T.-Y. Lee, H.-M. Lin, J Organomet. Chem. 427
(1992) 101.

726
C.-M. Liu et al. / Journal of Organometallic Chemistry 637–639 (2001) 723–726
[14] T.-Y. Dong, C.-C. Schei, M.-Y. Huang, T.-Y. Lee, S.-K. Yeh,
Y.-S. Wen, Organometallics 11 (1992) 573.
[20] C.-M. Liu, W.-Y. Liu, Y.-M. Liang, Y.-X. Ma, Synth. Commun.
30 (2000) 1755.
[15] T.-Y. Dong, T.-J. Ke, S.-M. Peng, S.-K. Yeh, Inorg. Chem. 28
(1998) 2103.
[21] C.-M. Liu, Y.-L. Guo, X.-L. Wu, Y.-X. Ma, J. Organomet.
Chem. 612 (2000) 172.
[16] T.-Y. Dong, T.-Y. Lee, S.-H. Lee, G.-H. Lee, S.-M. Peng,
Organometallics 13 (1994) 1337.
[17] L.-L. Lai, T.-Y. Dong, J. Chem. Soc. Chem. Commun. (1994)
2347.
[22] M.E. Wright, Organometallics 9 (1990) 853.
[23] T. Sammakia, H.A. Latham, J. Org. Chem. 61 (1996) 1629.
[24] S.-K. Kang, T.-G Baik, X.H. Jiao, Y.-T. Lee, Tetrahedron Lett.
40 (1999) 2383.
[18] T.-Y. Dong, C.-K. Chang, S.-H. Lee, L.-L. Lai, M.Y.-N. Chi-
ang, K.-J. Lin, Organometallics 16 (1997) 5816.
[19] C.-M. Liu, B.-H. Chen, W.-Y. Liu, X.-L. Wu, Y.-X. Ma, J.
Organomet. Chem. 598 (2000) 384.
[25] R.L. Beddoes, T. Cheeseright, J.Y. Wang, P. Quayle, Tetrahe-
dron Lett. 36 (1995) 283.
[26] E. Piers, E.J. McEachern, M.A. Romero, Tetrahedron Lett. 37
(1996) 1173.