Ir-catalyzed C-H activation in the synthesis of borylated ferrocenes and half sandwich compounds

Article abstract of DOI:10.1039/b403419h

The complex generated from 1/2 [Ir(OMe)(cod)]₂ and 4,4′-di-tert-butyl-2,2′-bipyridine catalyzes the regioselective borylation of ferrocenes, CpMn(CO)₃ and CpMo(CO)₃CH ₃ with a stoichiometric amount of B₂pin₂.

Full text of DOI:10.1039/b403419h

Ir-catalyzed C–H activation in the synthesis of borylated ferrocenes and
half sandwich compounds†
Anupama Datta, Axel Köllhofer and Herbert Plenio*
Institut für Anorganische Chemie, TU Darmstadt, Petersenstr. 18, 64287 Darmstadt, Germany.
E-mail: plenio@tu-darmstadt.de
Received (in Cambridge, UK) 5th March 2004, Accepted 21st April 2004
First published as an Advance Article on the web 27th May 2004
1
The complex generated from 2 [Ir(OMe)(cod)]2 and 4,4A-di-tert-
butyl-2,2A-bipyridine catalyzes the regioselective borylation of
ferrocenes, CpMn(CO)3 and CpMo(CO)3CH3 with a stoichio-
metric amount of B2pin2.
The reaction of ferrocene with B2pin2 in the presence of the
aforementioned Ir-complex was carried out at 126 °C for 24 h in
octane.‡ At this point the reaction mixture primarily consists of the
monoborylated product FcBpin formed in 60% yield, unreacted
ferrocene and 1,1A-Fc(Bpin)2, formed in a yield of less than 5%.
1,2-Fc(Bpin)2 and 1,3-Fc(Bpin)2 were not observed. More forcing
conditions did not lead to an appreciable increase in the yield of the
diborylated ferrocene, even when using a significant excess of
B2pin2. Similarly, isolated FcBpin could not be further function-
alized with B2pin2. Even at this early stage it has to be conceded
that the reactivity of ferrocene is significantly reduced as compared
to that of benzene; probably due to the much higher electron density
and steric hindrance of the former.
In order to evaluate the usefulness of C–H-activation for the
synthesis of substituted ferrocenes, a range of mono- and
disubstituted ferrocene derivatives were examined (Table 1).
Several borylated ferrocenes can be synthesized, but the reactions
are most effective with electron-deficient metallocenes. The
influence of electronic effects becomes quite clear when comparing
the reactivity of 1,1A-FcBr2 and 1,1A-Fc(CH3)2, with substituents of
comparable steric bulk. The borylation of the former compound is
facile (yield 81%), while 1,1A-Fc(CH3)2 is converted only in modest
12% yield. In both cases the respective 1,3,1A-isomers are formed
exclusively.
Functionalized ferrocenes are of interest due to their use as chiral
ligands in catalysis1 and as components of polymers,2 molecular
switches,3 drugs,4 and sensors.5 Most applications involve the use
of di-, tri- or even higher substituted ferrocenes. Consequently,
there is a permanent interest in new tools for the derivatization of
ferrocene.6 The most common method of functionalization is the
deprotonation with bases such as n-BuLi, to generate a potent
nucleophile followed by substitution reactions with various
electrophiles. A significant advantage of this approach is the
presence of ortho-directing groups for the metallation, which
allows the precise control of regioselectivity (or stereoselectivity)
for the synthesis of 1,2-disubstituted ferrocenes. On the downside,
organolithium reagents are highly reactive and impose restrictions
related to functional group tolerance. The chemistry of 1,3-dis-
ubstituted ferrocenes is much less explored even though they were
used by Deschenaux et al. for the preparation of organometallic
liquid crystals7 and by Plenio et al. for the synthesis of alternating
ferrocene acetylene polymers.8
The Ir-based complex prepared in situ from [IrCl(cod)]2 or
[Ir(OMe)(cod)]2 and 4,4A-di-tert-butyl-2,2A-bipyridine (dtbpy) was
shown to be an excellent catalyst for the direct functionalization of
unreactive hydrocarbons by C–H activation with bis(pinacolato)di-
boron (B2pin2).9
This methodology of aromatic C–H activation prompted us to
extend it to the chemistry of ferrocene, its derivatives and related
half sandwich compounds, to demonstrate the utility of Ir-catalyst
based CH-activation reactions in organometallic chemistry.
The coupling between ferrocene and stoichiometric amounts of
B2pin2 is catalyzed by 1/2[Ir(OMe)(cod)]2 and 4,4A-di-tert-butyl-
2,2A-bipyridine (dbtpy) in an inert solvent at elevated temperatures.
As noted by Ishiyama et al.,10 the reactions are fast in nonpolar
solvents (alkanes), as compared to coordinating solvents like DMF
or DME.
Oxygen containing functional groups at the ferrocene, like
FcCOOCH3, where reaction with the carbonyl groups could
possibly compete with borylation was found to be stable towards
B2pin2. The borylation of FcCOOMe and 1,1A-Fc(COOMe)2
resulted in monoborylated products in very good yields, again
suggesting that the presence of electron withdrawing groups on the
cyclopentadienyl ring results in a marked increase in the reactivity
Table 1 Borylation of ferrocenes and half-sandwich complexes
B2pin2
(equiv.)
Yield
(%)
Reactant
Producta
Ferrocene
Ferrocene
1.0
3.0
FcBpin
FcBpin
1,1A-Fc(Bpin)2
60
61
8
FcCOOCH3
1.5
1,3-FcBpin(COOCH3)
1,1A-FcBpin(COOCH3)
1,1A,3-FcBpin(COOCH3)2
1,1A-FcBpin(Br)
42
31
83
28
35
81
15
15
12
79
82
55
55
1,1A-Fc(COOCH3)2
FcBr
1.5
1.5
1,3-FcBpin(Br)
1,1A-Fc(Br)2
1,1A-Fc(COCH3)2
1,1-Fc(CH2OCH3)2
1,1A-Fc(CH3)2
CpMn(CO)3
CpMo(CO)3Me
FcBpin
1.5
1.0
1.0
1.0
1.0
1,1A,3-FcBpin(Br)2
1,1,3A-FcBpin(COCH3)2
1,1,3A-FcBpin(CH2OCH3)2
1,1,3A-FcBpin(CH3)2
(C5H4Bpin)Mn(CO)3
(C5H4Bpin)Mo(CO)3Me
FcI
1.0
b
c
FcBpin
1-Fc, 4-COMe-C6H4
a Reactions were carried out at octane reflux (126 °C) for 24 h unless
otherwise noted, 3 mol% catalyst [Ir(OMe)(cod)]2 + dtbpy. b Reaction with
N-iodosuccinimide, time 4 h, room temperature. c Suzuki coupling
(1-Ad)2PBn, Na2PdCl4 24 h, 65 °C, THF. The abbreviation Fc is used
indiscriminately for ferrocenyl, -diyl and -triyl. All compounds exist as
racemates. Yields of the products refer to isolated material after chromato-
graphic purification.
Scheme 1 Borylation of ferrocenes
† Electronic supplementary information (ESI) available: spectroscopic data
(1H, 13C NMR) and experimental procedures. See http://www.rsc.org/
suppdata/cc/b4/b403419h/
1508
C h e m . C o m m u n . , 2 0 0 4 , 1 5 0 8 – 1 5 0 9
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

of the respective ferrocene. As a typical example of mono-
substituted ferrocenes, methoxycarbonylferrocene, FcCOOMe,
gave two borylated products with Bpin substituted at the 3- and the
1A-position. The 1,3-borylated product is preferentially formed and
its yield was 1.3 times higher than that of the 1,1A-borylated
product.
The different rates for the borylation of FcCOOCH3 and 1,1A-
Fc(COOCH3)2 were studied by performing a competition reaction
with an equimolar mixture of mono- and disubstituted ferrocene
and B2pin2. The ratio of the yields of the corresponding borylated
products was 35 : 65, demonstrating the roughly twofold speed at
which the disubstituted product undergoes CH-activation. Sim-
ilarly, bromoferrocene derivatives were also tested. FcBr and
disubstituted 1,1A-Fc(Br)2 both show good reactivity towards
B2pin2. Again, FcBr gave two products with 1,3-Fc(Br)(Bpin)
dominating over 1,1A-Fc(Br)(Bpin), while 1,1A-Fc(Br)2 gave 1,1A,3-
Fc(Br)2(Bpin) in more than 85% yield.
Since electron deficient ferrocene derivatives were found to be
reactive towards CH-activation we were intrigued to study the
reactivity of Fc+PF62. However, no borylation took place in
octance, DMF, DMA or DME solvent at 150 °C/48 h.
When studying CpMn(CO)3 and CpMo(CO)3Me as examples of
more electron-deficient half sandwich complexes, both compounds
can be reacted to result in the respective borylated products in
excellent yields of 79% and 82% respectively.
At this point it has to be mentioned that the direct borylation of
ferrocene is also possible using BCl3 or BBr3 as pioneered by
Siebert et al. in the mid seventies.11 Nonetheless, the significant
advantages of the present approach are obvious: a) quite in contrast
to boron halides the present Ir-catalyzed reaction is highly tolerant
of various functional groups, and b) monosubstitution is possible
with high selectivity.
Successful borylation of arenes and heteroarenes with pinBH in
the presence of [Ir(OMe)(cod)]2 and dtbpy has been reported by
Ishiyama and Miyaura et al.12 Our attempts to use pinBH instead of
B2pin2 for the borylation of ferrocene and FcCOOCH3 under the
conditions mentioned for B2pin2 led to the corresponding borylated
products in modest yields of 10 and 15%, respectively.
To demonstrate the synthetic value of the borylated ferrocenes
we have studied the conversion of FcBpin. On treatment with N-
iodosuccinimide in acetonitrile FcBpin is converted into FcI in a
55% yield. Such halogenated ferrocenes are useful materials for
cross-coupling reactions. Similarly, FcBpin can be used in the
Suzuki-Miyaura cross coupling and the reaction with 4-bromoace-
tophenone results in formation of 1-Fc, 4-COMe-C6H4 in 55%
yield.
In conclusion, CH-activation reaction involving ferrocenes and
related half-sandwich compounds are powerful tools for the
synthesis of functionalized ferrocenes (preferentially electron-
deficient ones), which are complementary to existing techniques.
This method appears to be especially useful with half sandwich
complexes and it remains to be explored whether it can also be
applied to other p-perimeters. Notable is the functional group
tolerance of the present process, the 1,3-selective substitution and
the highly selective formation of the monosubstituted product.
This work was supported by the Deutsche Forschungsge-
meinschaft.
Notes and references
‡
General. All reactions and experiments were performed under an
atmosphere of dry argon using standard Schlenk techniques. For gas
chromatography, Perkin-Elmer Autosystem with a Varian CP-SIL-8
column was used.
General procedure for the Ir-catalyzed CH-activation: To a Schlenk tube
equipped with a reflux condenser, [Ir(OMe)(cod)]2 (0.015 mmol, 10.0 mg),
dtbpy (0.03 mmol, 4.7 mg), and B2pin2 (1.0 mmol, 254.0 mg) were added.
Octane (7 ml) and the respective ferrocene or half sandwich complex (2.0
mmol) were added, and the mixture was stirred at the given temperature for
the given period of time (typically at reflux for 24 h). The reaction mixture
was analyzed with GC and the pure product was isolated by column
chromatography (silica gel, cyclohexane/ethyl acetate) and the purity
checked by GC and NMR. Isomers were separated by chromatography.
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The results presented here raise some interesting questions with
respect to the mechanism of Ir-catalyzed CH-activation reactions.
Very recently both Periana, Goddard et al.13 and Sakaki et al.14
proposed in two independent publications that Ir(III) and Ir(
the relevant oxidation states of the metal in the catalytic cycle.
However, there can be little doubt that Ir( ) has considerable
V) are
V
oxidative power and should oxidize even electron-deficient ferro-
cenes.15 On the other hand, the successful transformation of
ferrocenes demonstrates that metallocenes do not inhibit the active
Ir-complex.
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C h e m . C o m m u n . , 2 0 0 4 , 1 5 0 8 – 1 5 0 9
1509