Suzuki-Miyaura coupling in the presence of (2,2,2-triferrocenylethyl)diphenylphosphane

Article abstract of DOI:10.1016/j.jorganchem.2007.10.053

The electron rich and sterically bulky title phosphane was prepared and efficiently applied in the palladium catalyzed Suzuki-Miyaura cross-coupling reaction. With electron rich aryl chlorides and bromides the yields and reaction times were significantly improved by microwave heating.

Full text of DOI:10.1016/j.jorganchem.2007.10.053

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Journal of Organometallic Chemistry 693 (2008) 357–360
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Note
Suzuki–Miyaura coupling in the presence of
(2,2,2-triferrocenylethyl)diphenylphosphane
*
Jose Ramon Garabatos-Perera, Holger Butenschon
¨
Institut fu¨r Organische Chemie, Leibniz Universita¨t Hannover, Schneiderberg 1B, D-30167 Hannover, Germany
Received 27 August 2007; received in revised form 25 October 2007; accepted 31 October 2007
Available online 6 November 2007
Abstract
The electron rich and sterically bulky title phosphane was prepared and efficiently applied in the palladium catalyzed Suzuki–Miyaura
cross-coupling reaction. With electron rich aryl chlorides and bromides the yields and reaction times were significantly improved by
microwave heating.
ꢀ 2007 Elsevier B.V. All rights reserved.
Keywords: Cross-coupling; Ferrocene ligands; Triferrocenylmethane; Phosphanes; Palladium; Suzuki–Miyaura coupling
Much attention has lately been devoted to the chemistry
of ferrocene derivatives, which combine chemical versatil-
ity with high thermal stability. These, together with its
exceptional electrochemical properties, make ferrocene-
based complexes promising candidates for the preparation
of new materials with applications in organic synthesis,
catalysis and material science [1]. Although a wide range
of molecular structures containing more than one ferrocene
unit have been described [2–10], triferrocenylmethyl deri-
vates have been investigated little so far, and this is most
likely because of the difficulties encountered in the synthe-
sis of the triferrocenylmethyl scaffold. Triferrocenylmetha-
nol has been previously synthesized by Pauson and Watts
by the addition of ferrocenyllithium to diferrocenylketone.
The stumbling block in this sequence actually is the avail-
ability of the starting materials rather than their conversion
to triferrocenylmethanol [11].
derivatives such as 1 and 10-substituted derivatives 2 [12].
Herein we disclose results of the use of this new methodol-
ogy in the synthesis of a triferrocenylmethane based phos-
phane ligand for the palladium catalyzed Suzuki–Miyaura
cross-coupling reaction.
R
R
Fe
Fe
Fe
Fe
Fe
SnBu3
Bu3Sn
Fe
SnBu3
R = OH, tBu
2
R = H, Me, Et, Bu,sBu, tBu
1
As part of a program focussing on the syntheses and
applications of triferrocenylmethane derivatives, we
recently reported a general and practically useful method
for the synthesis of substituted triferrocenylmethane
Electron rich and bulky monodentate phosphanes have
recently been recognized as important and useful ligands
in palladium(0) catalyzed processes. Most attention has
recently focused on ligands such as tri-tert-butylphosphane
(3), dialkyl(biphenyl)phosphanes 4 and pentaarylferroce-
nylphosphane (5), since they have been proven to be
*
Corresponding author. Tel.: +49 511 762 4661; fax: +49 511 762 4616.
E-mail address: holger.butenschoen@mbox.oci.uni-hannover.de (H.
Butenscho¨n).
0022-328X/$ - see front matter ꢀ 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2007.10.053

358
J.R. Garabatos-Perera, H. Butenscho¨n / Journal of Organometallic Chemistry 693 (2008) 357–360
unique, highly efficient ligands for a large number of tran-
sition metal catalyzed transformations such as C–C cou-
pling reactions (Suzuki–Miyaura, Heck, Stille, Sonogashira,
Negishi and enolate coupling) and C–O and C–N bond for-
mation reactions [13].
became possible by microwave irradiation (250 W,
150 ꢁC, 8 bar) [16]. In particular, the reaction of 4-methyl-
bromobenzene (12) gave a fourfold higher yield than with
conventional heating, and the reaction time was reduced
from 24 h to 1 h. For 4-chlorobenzonitrile (11) the yield
increased from 92% to 95% with a reduction in reaction
time from 72 h to 1 h. The highest yield (97 %) was
achieved by using 4-bromoacetophenone (16) under micro-
wave irradiation (entry 13). Initial experiments showed
Pd(dba)2 to be a better palladium source than Pd(OAc)2
(entries 1–3).
PtBu2
tBu
Ph
Ph
Ph
Ph
Fe
Ph
PtBu2
P
tBu
tBu
R
Suzuki–Miyaura coupling reactions were first reported
in 1981 [17] and have since then been further developed
by modifications in the metal catalyst, the phosphane
ligand, and reaction conditions such as solvent or the intro-
duction of microwave heating [18–22]. Some of the results
shown in Table 1 compare quite well with those of other
groups. For example, the reaction with 4-bromoacetophe-
none (16, entry 13) gives 97% yield, while the reaction
achieved 91% in a phosphane free, microwave heated reac-
tion. Similarly, the reaction of 4-methoxybromobenzene
(14, entry 11, 88%) compares to 86% under such conditions
[21]. Although more sophisticated diphosphine ligands give
better results in some cases [19], the results obtained for 4-
chlorobenzonitrile in the presence of 7 particularly with
aryl chloride 11 compare very well with those obtained
e.g. by Hierso with a much more complicated ferrocene-
based phosphane [23] or by Buchwald with 2-(di-tert-buty-
lphosphino)biphenyl [15].
R: electron withdrawing or
electron delivering group
ino, m orp-Position
5
3
4
The extraordinary activity of palladium catalysts
formed with these electron rich and sterically bulky phos-
phanes in coupling reactions involving aryl chlorides has
been explained by an increased propensity of the more elec-
tron rich catalyst to an oxidative addition of the aryl halide
and an easier decomplexation of one phosphane ligand
finally resulting in the formation of the catalytically active
Pd(0)L species (L = phosphane) [14]. The so far limited
structural diversity of electron rich and sterically bulky
monophosphanes causes major interest in the synthesis of
novel bulky and electron rich monophosphanes.
In our earlier work we had developed a procedure to
incorporate the sterically bulky and electron rich triferroce-
nylmethyl fragment by reaction of the triferrocenylmethyl
carbenium ion with nucleophiles. The carbenium ion was
easily generated by treatment of triferrocenylmethanol (6)
with triphenylmethyl tetrafluoroborate [12]. According
to this procedure treatment of the triferrocenylcarbeni-
um with lithiated methyldiphenylphosphane gave
phosphane 7 in 70 % yield. 7 was characterized spectro-
scopically.
In conclusion, we have presented the synthesis of (2,2,2-
triferrocenylethyl)diphenylphosphane and demonstrated
its suitability as a ligand in the palladium catalyzed
Suzuki–Miyaura cross-coupling reaction with several aryl
bromides and 4-chlorobenzonitrile. Improved yields and
shorter reaction times were realized under microwave
irradiation.
1. Experimental
PPh2
OH
+
–
1. Ph C BF
3
4
1.1. (2,2,2-Triferrocenylethyl)diphenylphosphane (7)
2. Ph PCH Li
2
2
Fe
Fe
Fe
Fe
THF
70 %
At 25 ꢁC, a well stirred suspension of triferrocenylmeth-
anol (6) (0.666 g, 1.1 mmol) in 50 mL of anhydrous diethyl
ether was treated with Ph3CBF4 (0.377 g, 1.1 mmol), and
the solution was allowed to react until no starting material
remained (TLC, CH2Cl2). The green precipitate was
washed three times with 3 · 50 mL of anhydrous DEE
each, dissolved in 50 mL of anhydrous THF and cooled
to ꢀ78 ꢁC. To this solution (lithiomethyl)diphenylphos-
phane borane complex, which was obtained from methyldi-
phenylphosphane borane complex (0.466 g, 2.1 mmol),
s-BuLi (1.86 mL, 1.8 M in DEE, 1.0 mmol) and 9.32 mL
of THF [24], was added. The reaction mixture was allowed
to warm to 25 ꢁC, and after 1 h 40 mL of Et2NH was
added. After stirring for 2 d at 25 ꢁC the volatiles were
removed at reduced pressure. The remaining solid was
washed with anhydrous CH2Cl2 until no product remained
Fe
Fe
6
7
Phosphine 7 was tested in the Suzuki–Miyaura coupling
reaction of phenylboronic acid and selected electron poor
and as well as electron rich arylbromides and chlorides.
Results are summarized in Table 1.
The results indicate that phosphane 7 promotes the
Suzuki–Miyaura coupling of aryl bromides and chlorides.
Best results were achieved with electron poor aryl halides
9–11. More electron rich aryl halides such as bromoben-
zene (8) or 4-methylbromobenzene (12) give poorer yields.
Higher yields and significantly shorter reaction times

J.R. Garabatos-Perera, H. Butenscho¨n / Journal of Organometallic Chemistry 693 (2008) 357–360
359
Table 1
Pd-catalyzed Suzuki–Miyaura cross-coupling reactions of aryl halides with phenylboronic acid
X
B(OH) 2
2 mol% [Pd]
2 mol% 7
R
+
Base
THF
R
Entry
Aryl halide
[Pd]
Base
Producta
Reaction time [h]
Isolated yield [%]
1b
2c
C6H5Br (8)
C6H5Br (8)
C6H5Br (8)
Pd(OAc)2
Pd(OAc)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
CsCO3
KF
KF
KF
KF
KF
KF
KF
KF
KF
KF
KF
KF
17
17
17
18
19
20
21
20
21
22
23
24
25
24
24
19
19
72
72
24
1
1
1
1
1
30
46
54
95.5
97
92
13
95
52
77
88
62
97
3b
4b
4-NCC6H4Br (9)
4-O2NC6H4Br (10)
4-NCC6H4Cl (11)
4-MeC6H4Br (12)
4-NCC6H4Cl (11)
4-MeC6H4Br (12)
2-MeC6H4Br (13)
4-MeOC6H4Br (14)
2-Bromo-naphtalene (15)
4-Bromoacetophenone (16)
5b
6b
7b
8d
9d
10d
11d
12d
13d
a
1
Identified spectroscopically; [15].
60–65 ꢁC.
b
c
80 ꢁC.
d
lW: 250 W, 150 ꢁC, 8 bar.
and the ammonium salts were removed by filtration
through Celite. The solvent was removed at reduced pres-
sure to yield an orange solid, which was washed with cold
degassed methanol, resulting in pure (1H, 13C NMR)7
(0.616 g, 0.8 mmol, 70%).
1.3. General procedure for the synthesis of biaryls assisted by
microwave irradiation (GP2)
The palladium salt (0.02 mmol), the boronic acid
(0.183 g, 1.5 mmol) and KF (0.174 g, 3.0 mmol) are added
to a heavy-walled microwave vial under argon The vial is
evacuated and then refilled with argon three times. Next
the solution of 7 (2 mL, 0.01 M in THF, 0.02 mmol,
2.0 mL) and the arylhalide (1.0 mmol) are added, the vial
closed, and the contents of the flask is irradiated for 1 h
with a power of 250 W heating until a maximum of
150 ꢁC. The mixture is hydrolyzed by addition of 25 mL
of water, and the mixture is diluted with 25 mL of diethyl
ether. The organic layer is washed with 3 · 25 mL of
H2O, dried over MgSO4, and the solvent is removed at
reduced pressure. The biaryl is isolated by column
chromatography.
3
1H NMR (400 MHz, CDCl3): d = 3.6 (d, J = 4.1 Hz,
2H, CH2), 3.98 (s, 15H, HCp), 4.12 + 4.12 (AA0BB0 line sys-
tem, 2 · 6H, HCpR), 7.2–7.4 (m, 10H, Ph) ppm. 13C NMR
(100 MHz, BB, HMQC, HMBC, CDCl3): d = 40.4 (d,
1
2JP,C = 14.8 Hz, CFc3), 48.4 (d, JP,C = 18.6 Hz, CH2),
66.3 (br s, CpR-CH), 68.6 (d, JP,C = 5.3 Hz, CpR–CH),
69.0 (Cp), 99.3 (d, JP,C = 3.8 Hz, CpR–CR), 128.1 (d,
JP,C = 1.6 Hz, Ph), 133.1 (d, JP,C = 4.9 Hz, Ph), 141.1 (d,
JP,C = 3.6 Hz, Ph), 128.0 (Ph) ppm. 31P NMR
(121.5 MHz, CDCl3): d = ꢀ21.78 (PPh2) ppm. MS (ESI,
ES+): m/z = 767 [M++H], 783 [M++O]. HRMS (ESI)
(C44H40Fe3P): calc. 767.0916; found, 767.0912 [M+H].
1.2. General procedure for the synthesis of biaryls (GP1)
Acknowledgements
The palladium salt (0.02 mmol), the boronic acid
(0.183 g, 1.5 mmol) and KF (0.174 g, 3.0 mmol) are added
to a Schlenk tube under argon. The Schlenk tube is evacu-
ated and then refilled with argon three times. Next the solu-
tion of 7 (2.0 mL, 0.01 M in THF, 0.02 mmol) and the
arylhalide (1.0 mmol) are added, the Schlenk tube is closed
with a stopper, and the reaction is stirred at the indicated
temperature for the indicated amount of time. The mixture
is hydrolyzed by addition of 25 mL of water, and the mix-
ture is diluted with 25 mL of diethyl ether. The organic
layer is washed with 3 · 25 mL of H2O, dried over MgSO4,
and the solvent is removed at reduced pressure. The biaryl
is isolated by column chromatography.
This work was kindly supported by the Deutsche Fors-
chungsgemeinschaft. We thank Octel Deutschland GmbH
for a donation of ferrocene.
References
[1] A. Togni, T. Hayashi (Eds.), Ferrocenes – Homogeneous Catalysis,
Organic Synthesis, Materials Science, VCH, Weinheim, 1995.
[2] U.H.F. Bunz, J. Organomet. Chem. 683 (2003) 269.
[3] B. Bildstein, W. Skibar, M. Schweiger, H. Kopacka, K. Wurst, J.
Organomet. Chem. 622 (2001) 135.
[4] P. Jutzi, N. Lenze, B. Neumann, H.-G. Stammler, Angew. Chem. 113
(2001) 1469;

360
J.R. Garabatos-Perera, H. Butenscho¨n / Journal of Organometallic Chemistry 693 (2008) 357–360
[13] A.F. Littke, G.C. Fu, Angew. Chem. 114 (2002) 4350;
P. Jutzi, N. Lenze, B. Neumann, H.-G. Stammler, Angew. Chem.,
Int. Ed. 40 (2001) 1423.
A.F. Littke, G.C. Fu, Angew. Chem., Int. Ed. 41 (2002)
4176.
[14] U. Christmann, R. Vilar, Angew. Chem. 117 (2005) 370;
U. Christmann, R. Vilar, Angew. Chem., Int. Ed. 44 (2005)
366.
[5] A. Althoff, D. Eisner, P. Jutzi, N. Lenze, B. Neumann, W.W.
Schoeller, H.-G. Stammler, Chem. Eur. J. 12 (2006) 5471.
[6] E.I. Klimova, T. Klimova Berestneva, A. Cinquantini, M. Corsini,
P. Zanello, R.A. Toscano, S. Hernandez-Ortega, M. Martinez Garcia,
Org. Biomol. Chem. 1 (2003) 4458.
[7] F. Barriere, R.U. Kirss, W.E. Geiger, Organometallics 24 (2005) 48.
[8] T.-Y. Dong, S.-W. Chang, S.-F. Lin, M.-C. Lin, Y.-S. Wen, L. Lee,
Organometallics 25 (2006) 2018.
[15] J.P. Wolfe, R.A. Singer, B.H. Yang, S.L. Buchwald, J. Am. Chem.
Soc. 121 (1999) 9550.
[16] M. Larhed, A. Hallberg, J. Org. Chem. 61 (1996) 9582.
[17] N. Miyaura, T. Yanagi, A. Suzuki, Synth. Commun. 11 (1981) 513.
[18] N. Miyaura, A. Suzuki, Chem. Rev. 95 (1995) 2457.
[19] J. Tsuji, Palladium Reagents and Catalysts, Wiley, Chichester, 2004.
[20] N. Miyaura, Top. Curr. Chem. 219 (2002) 11.
[21] N.E. Leadbeater, M. Marco, Org. Lett. 4 (2002) 2973.
[22] A. Suzuki, in: D. Astruc (Ed.), Modern Arene Chemistry, Wiley-
VCH, Weinheim, 2002, p. 53.
[23] J.-C. Hierso, A. Fihri, R. Amardeil, P. Meunier, H. Doucet, M.
Santelli, B. Donnadieu, Organometallics 22 (2003) 4490.
[24] T. Imamoto, T. Oshiki, T. Onozawa, T. Kusumoto, K. Sato, J. Am.
Chem. Soc. 112 (1990) 5244.
[9] J.B. Heilmann, M. Scheibitz, Y. Qin, A. Sundararaman, F. Jaekle,
T. Kretz, M. Bolte, H.-W. Lerner, M.C. Holthausen, M. Wagner,
Angew. Chem. 118 (2006) 934;
J.B. Heilmann, M. Scheibitz, Y. Qin, A. Sundararaman, F. Jaekle,
T. Kretz, M. Bolte, H.-W. Lerner, M.C. Holthausen, M. Wagner,
Angew. Chem., Int. Ed. 45 (2006) 920.
[10] S. Barlow, D. O’Hare, Chem. Rev. 97 (1997) 637.
[11] P.L. Pauson, W.E. Watts, J. Org. Chem. 27 (1962) 3880.
[12] J.R.G. Perera, R. Wartchow, H. Butenscho¨n, J. Organomet. Chem.
689 (2004) 3541.