BARF-catalyzed C-H bond alkenylation and alkylation of ferrocenes

Article abstract of DOI:10.1021/om300348e

[Ir(cod)₂]BARF [BARF = tetrakis(3,5-trifluoromethylphenyl) borate] catalyzed the directed alkenylation and alkylation of ferrocenes to form a variety of tri- and disubstituted ferrocenes. Mechanistic investigation revealed several putative intermediates along with the importance of COD (1,5-cyclooctadiene), as a diene ligand, and a possible catalyst deactivation pathway. On the basis of the mechanistic investigation, catalytic activity was further improved.

Full text of DOI:10.1021/om300348e

Communication
pubs.acs.org/Organometallics
[Ir(cod)2]BARF-Catalyzed C−H Bond Alkenylation and Alkylation of
Ferrocenes
Satoshi Takebayashi and Takanori Shibata*
Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, Okubo, Shinjuku,
Tokyo, 169-8555, Japan
S
* Supporting Information
ABSTRACT: [Ir(cod)2]BARF [BARF = tetrakis(3,5-
trifluoromethylphenyl)borate] catalyzed the directed alkenyla-
tion and alkylation of ferrocenes to form a variety of tri- and
disubstituted ferrocenes. Mechanistic investigation revealed
several putative intermediates along with the importance of
COD (1,5-cyclooctadiene), as a diene ligand, and a possible
catalyst deactivation pathway. On the basis of the mechanistic
investigation, catalytic activity was further improved.
errocene and its derivatives are among the most versatile
organometallic compounds because of their unique
we report the first catalytic directed alkenylation and alkylation
of ferrocenes.
F
structures, chemical and thermal stabilities, and redox proper-
ties.1 These redox properties have found widespread application
in fields such as material science and medicinal research.2
Recent applications include use in nonvolatile organic
memory,3a as an electrolyte for dye-sensitized solar cells,3b
and as a reversible luminescence switch.3c Further, planar chiral
ferrocenyl ligands are among the most successful chiral ligands
in both academia and industry.4 Ferrocene and its derivatives
are usually functionalized using stoichiometric methods, such as
electrophilic substitution, or lithiation of the cyclopentadienyl
(Cp) ring(s);1,4 however, these methods suffer from poor atom
economy.
Functionalizations via transition-metal-catalyzed C−H acti-
vation of the Cp ring(s) are potentially more atom-efficient
alternatives. However, only a few catalytic C−H activation
reactions of ferrocenes have been reported to date.5 Schmalz et
al. reported the first catalytic C−H activation of ferrocenes
using a Cu-catalyzed intramolecular carbene insertion into a
Cp−H bond.5a However, this method is limited in terms of
scope of substrates due to its intramolecular nature. Ir(I)-
catalyzed C−H borylation of ferrocenes was also utilized for
functionalizing ferrocenes, albeit with problematic regioselecti-
vity.5b More recently, oxazoline-directed arylation of ferrocenes
was reported using a Pd(II) complex. Most of the reactions in
this report are, however, stoichiometric, and the yields of the
catalytic reactions were generally low.5c There are a number of
reports on stoichiometric directed C−H activation of
ferrocenes via electrophilic substitution of electron-rich Cp
ring(s).6 In contrast, reports on stoichiometric directed C−H
activation of ferrocenes via oxidative addition are scarce.7
We recently reported that a series of cationic [Ir(cod)2]X (X
= OTf, BF4, BARF) complexes, combined with diphosphine,
catalyzed the directed C−H activation of sp2 C−H bonds.8
Further, we reported that these catalysts could activate sp3 C−
H bonds.9 With these highly active cationic Ir catalysts in hand,
Table 1 summarizes the result of catalyst screening using 2-
ferrocenylpyridine (1a) and 2 equiv of diphenylacetylene (2a).
Under the reaction conditions used for the activation of sp3 C−
H bonds,9 disubstituted ferrocene 3a formed in low yield due
to the low conversion of 1a (entry 1). Use of electron-rich or
-poor phosphines did not significantly improve catalyst activity
(entries 2 and 3). Unexpectedly, when conducted in the
absence of phosphine ligands, the reaction was complete in 2 h
to afford trisubstituted ferrocene 4a in moderate yield (entry
4). There have been a few reports of C−H activation catalyzed
by iridium diene complexes.10 Neutral Ir(I) catalyst was
inactive toward the reaction (entry 5).8,9 Interestingly, although
Rh(I) complexes are active toward the alkenylation and
alkylation of arenes and olefins,11 the Rh analogue, [Rh-
(cod)2]BARF, did not catalyze the reaction at all (entry 6). An
attempt to selectively form disubstituted ferrocene 3a with 1
equiv of 2a resulted in low selectivity, likely due to strong
coordination of the pyridyl group (entry 7). The yield of 4a was
improved when the reaction was conducted in toluene at 110
°C (entry 8).
The scope of substrates was examined under the reaction
conditions of entry 8 in Table 1, using 4 equiv of an alkyne or
alkenes 2 (Table 2). In entries 1−10, trisubstituted ferrocenes 4
were obtained as the major products with anti-Markovnikov
selectivity. The reaction proceeded smoothly with a variety of
terminal alkenes to form trisubstituted ferrocenes 4b−j (entries
1−9). Functional groups such as ester, ketone, and boronic
ester groups remained intact under the reaction conditions
(entries 2, 3, and 5). The activated internal alkene 2k formed
the trisubstituted ferrocene 4k as a diastereomeric mixture
(major:minor = 9:1) (entry 10). The relative stereochemistry of
Received: April 26, 2012
Published: May 22, 2012
© 2012 American Chemical Society
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Communication
internal alkene and a terminal alkyne were inactive toward the
reaction (entries 11 and 12).11,12
Table 1. Optimization of Reaction Conditions
Next, the scope of the directing groups was examined under
the reaction conditions used in Table 2 (Figure 1). The
a
a
entry
ligand
time (h)
3a (%)
4a (%)
Figure 1. Scope of directing groups.
1
2
rac-BINAP
12
25
24
2
7
0
1
8
b
DBPFc
14
19
0
c
3
P(4-FC6H4)3
none
d
reaction between 1-octene (2j) and N-phenylmethylferrocenyl
imine formed the trisubstituted ferrocene 4n. Use of an
isoquinolyl directing group resulted in the formation of a
racemic mixture of planar chiral disubstituted ferrocene 3o in
high selectivity due to steric repulsion within 3o.13
Diphenylphosphine oxide was also used as a directing group
to form planar chiral ferrocenyl phosphine oxide 3p, albeit in
low yield. The results in Table 2 and Figure 1 demonstrate the
versatility and high regioselectivity that have not been achieved
previously in the catalytic C−H activation of ferrocene
derivatives.
4
59
e
5
none
24
29
3
trace
0
0
f
6
none
0
g
7
none
40
trace
31
h
d
8
none
2
77
a
b
c
NMR yields. 1,1′-Bis(di-tert-butylphosphino)ferrocene. P(4-
FC6H4)3 (20 mol %) was used. Isolated yields. [Ir(cod)Cl]2 (5
mol %) was used in place of [Ir(cod)2]BARF. [Rh(cod)2]BARF was
used in place of [Ir(cod)2]BARF. One equiv of 2a was used. In
toluene, at 110 °C.
d
e
f
g
h
We carried out a mechanistic investigation using variable-
temperature NMR analyses: we used [Ir(cod)2]BF4 in place of
[Ir(cod)2]BARF in order to simplify NMR spectra and
submitted it to the reaction of a 2-ferrocenylpyridine (1a) or
2-phenylpyridine (1q) as an analogue of 1a, with ethyl acrylate
(2c). CDCl3 was chosen as a solvent due to the low solubility
of [Ir(cod)2]BF4 in toluene-d8. The reaction between [Ir-
(cod)2]BF4 and 1 equiv of 1a or 1q proceeded on mixing at
−40 °C to form bispyridine complex 5a or 5q with
concomitant release of 1,5-cyclooctadiene (COD) and
unreacted [Ir(cod)2]BF4 in a ratio of about 1:1:1 (Scheme
1).14 The structures of 5a and 5q were characterized using 1H,
13C, gCOSY, and gHMQC NMR experiments. Similar
coordination of substrate was not observed when [Ir((R)-
binap)(cod)]BF4 and 1a were mixed at 23 °C. Thus, the
nonlabile COD ligand is likely one of the factors that decreases
the catalytic activity of [Ir(phosphine)2(cod)]BF4 complexes, as
seen in Table 1, entries 1−3. We also noted that the Ir center in
[Ir(cod)2]BF4 is more electron-poor than that of [Ir((R)-
binap)(cod)]BF4 based on 1H and 13C{1H} NMR.14 This
electronic difference will also affect the activity of these
complexes toward the catalytic reaction.
the major isomer of 4k was determined to be meso by X-ray
crystallography (see Supporting Information). A nonactivated
Table 2. Scope of an Alkyne and Alkenes
Upon the addition of 1 equiv of ethyl acrylate (2c) to the
mixture of 5a, [Ir(cod)2]BF4, and COD, the reaction proceeded
at 0 °C to form a mixture of several species that could not be
identified. In contrast, the reaction of 2c with the mixture of 5q,
[Ir(cod)2]BF4, and COD was complete in about 10 min at 23
°C to form the Ir-ester complex 6 almost exclusively along with
COD and its isomerized products (Scheme 1). All methylene
protons in 6 appeared as nonequivalent signals in the 1H NMR
spectrum due to the conformational rigidity of the ethylene
tether. The 13C signal of the carbonyl carbon appeared at 196
ppm, shifted downfield by 23 ppm from the signal for the free
pyridine-ester product.15 This downfield shift indicates η1-
coordination of the carbonyl oxygen.16
a
a
entry
2
4 (%)
entry
2
4 (%)
e
1
2
2b
2c
2d
2e
2f
79
87
52
84
61
74
7
2h
2i
58
71
f
8
b
3
9
2j
83
4
10
2k
2l
>99
0
bc
,
g
5
6
11
d
d
2g
12
2m
0
d
a
b
c
Isolated yields. 3 h. Yield after converting Bpin into OH. Two
equiv of 2g or 2m was used. 5 h. Yield after converting OSiMe3 into
e
f
g
OH. 16 h.
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Communication
Scheme 1. Reaction between [Ir(cod)2]BF4, 1a or 1q, and 2c
Scheme 2. Formation of the Ir-π-Allyl Complex 8
NaBARF, the reaction of 1a with 2j in toluene at 110 °C
concluded within 3 h, and the trisubstituted product 4j was
obtained in 91% yield. This corresponds to a nearly 56-fold
increase of TOF compared to the same reaction using 5 mol %
of [Ir(cod)2]BARF. On the basis of these mechanistic
investigations, we proposed a catalytic cycle that proceeds via
an oxidative addition/reductive elimination pathway (Scheme
3).
Scheme 3. Proposed Catalytic Cycle
Observation of the Ir-hydride species that may form via
oxidative addition of 1q was attempted using MeCN (4 equiv/
Ir) as a trapping agent. Indeed, in the presence of MeCN, stable
Ir-hydride species 7 formed when the mixture of 5q,
[Ir(cod)2]BF4, and COD was reacted at −20 °C (Scheme 1).
The COD ligand in 7 was intact in the presence of hydride
ligand at 23 °C.17 The 1H signals of Ir−H and Ir−NCMe were
observed at −15.6 and 2.31 ppm, respectively. The stereo-
chemistry of complex 7 was deduced based on the Ir−H
chemical shifts of analogous complexes.17 The Ir-hydride 7
reacted with alkene 2c at 23 °C to form the Ir-ester complex 6
with concomitant release of MeCN. The putative Ir-alkyl-aryl
complex that may form via insertion of 2c into the Ir−H bond
could not be detected due to rapid reductive elimination and
subsequent formation of 6. Results of these stoichiometric
reactions indicate that the catalytic reaction using ferrocenyl
substrates most likely proceeds via oxidative addition of the Cp
ring.7
Oxidative addition of 1q was faster in the presence of MeCN
(started at −20 °C) than in the absence (started at 0 °C), most
likely due to MeCN-assisted faster dissociation of 1q from the
bispyridine complex 5q. This assumption was successfully
applied to improve the catalytic activity. Thus, the reaction
between 1a and 2j conducted using 5 mol % of [Ir(cod)2]-
BARF (in toluene, 110 °C, 19.5 h) slowly formed the
disubstituted product 3j and the trisubstituted product 4j in
12% and 4% yield, respectively. However, in the presence of
MeCN (10 equiv/Ir), the same reaction was complete in 6 h to
form 4j in 82% yield, which means nearly 26-fold increase of
TOF. Detailed kinetic studies will enable us to confirm the
origin of the rate acceleration.
When the mixture of 5q, [Ir(cod)2]BF4, and COD was
heated to 50 °C in the absence of 2c, the Ir-π-allyl complex 8
formed (Scheme 2). Complex 8 did not react with alkene 2c
even at 80 °C. Thus, the formation of 8 is likely one of the
catalyst deactivation pathways. Indeed, when an Ir complex
possessing only a COD as a ligand was used, which was
prepared from 2.5 mol % of [Ir(cod)Cl]2 and 5 mol % of
In conclusion, this communication presents the first directed
alkenylation and alkylation of ferrocenes catalyzed by [Ir-
(cod)2]BARF. A variety of alkenes and directing groups were
successfully employed to selectively form trisubstituted
ferrocenes and disubstituted ferrocenes. The mechanistic
investigation revealed that the reaction likely proceeds via a
directed oxidative addition of the Cp ring to the [Ir(cod)(L)2]+
species. The COD ligand was intact at least under the
stoichiometric condition. Further, a possible catalyst deactiva-
tion pathway was proposed. These mechanistic investigations
were utilized to logically improve the catalyst activity. We are
currently investigating the enantioselective version of the
reaction.
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Communication
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ASSOCIATED CONTENT
* Supporting Information
The experimental procedure and physical properties of new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
■
S
(15) Kuninobu, Y.; Nishina, Y.; Okaguchi, K.; Shouho, M.; Takai, K.
Bull. Chem. Soc. Jpn. 2008, 81, 1393.
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Acta 1999, 291, 91. (b) Daley, C. J. A.; Bergens, S. H. J. Am. Chem. Soc.
2002, 124, 3680.
AUTHOR INFORMATION
Corresponding Author
*Tel and Fax: +81-3-5286-8098. E-mail: tshibata@waseda.jp.
Notes
■
(17) Martín, M.; Sola, E.; Torres, O.; Plou, P.; Oro, L. A.
Organometallics 2003, 22, 5406.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the Japan Society of the
Promotion of Science (JSPS) and Waseda University Grant
for Special Research Projects (No. 2011A-896). We greatly
appreciate the assistance of the Waseda University Materials
Characterization Central Laboratory.
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