Iron-catalyzed borylation of alkyl, allyl, and aryl halides: Isolation of an iron(I) boryl complex

Article abstract of DOI:10.1021/om500847j

Activation of B₂pin₂ with ^tBuLi facilitates the Fe-catalyzed borylation of alkyl, allyl, benzyl, and aryl halides via the formation of Li[B₂pin₂(^tBu)] (1). The reaction of 1 with a representative iron phosphine precatalyst generates the unique iron(I) boryl complex [Fe(Bpin)(dpbz)₂] (2).

Full text of DOI:10.1021/om500847j

Communication
pubs.acs.org/Organometallics
Iron-Catalyzed Borylation of Alkyl, Allyl, and Aryl Halides: Isolation of
an Iron(I) Boryl Complex
Robin B. Bedford,*,† Peter B. Brenner,† Emma Carter,‡ Timothy Gallagher,† Damien M. Murphy,‡
and Dominic R. Pye†
†School of Chemistry, University of Bristol, Cantock’s Close, Bristol BS8 1TS, U.K.
‡School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff CF10 3AT, U.K.
S
* Supporting Information
t
ABSTRACT: Activation of B2pin2 with BuLi facilitates the Fe-
catalyzed borylation of alkyl, allyl, benzyl, and aryl halides via the
formation of Li[B2pin2(tBu)] (1). The reaction of 1 with a
representative iron phosphine precatalyst generates the unique
iron(I) boryl complex [Fe(Bpin)(dpbz)2] (2).
a
lkylboronic acid derivatives are of great synthetic interest
and can be prepared by a variety of methods.1 A recent
Table 1. Optimization of Iron-Catalyzed Borylation
A
and highly attractive methodology, developed originally by
Marder and co-workers,2 relies on the borylation of alkyl
halides with diboron esters, in particular bis(pinacolato)-
diboron (B2pin2) (Scheme 1). Originally, this method required
b
entry
[Fe-cat]
activator
yield, %
c
1
[FeCl2(dppe)]
KF + MgBr2
0
3
c
2
KOtBu + MgBr2
Scheme 1
c
3
NEt3 + MgBr2
6
4
EtMgBr
38
71
71
80
85
90
90
0
c
5
tBuLi + MgBr2
d
6
[FeCl2(dppe)]
FeBr2
7
Cu catalysts,2,3 but the scope has been expanded to include
Pd-,4 Ni-,5 and, most recently, Zn-based catalysts.6 The
equivalent iron-catalyzed process is highly desirable due to
iron’s low cost and toxicity.7 We report that both phosphine-
containing and coligand-free iron-based catalysts can be
employed in the reaction to excellent effect. Furthermore, we
show that a unique iron(I) boryl complex can be isolated under
catalytically relevant conditions.
8
FeBr2 + xantphos
FeBr2 + dcpe
[FeCl2(dcpe)]
none
9
10
11
12
13
14
15
16
c
[FeCl2(dcpe)]
MgBr2
0
e
c
[FeCl2(dcpe)]
tBuLi + MgBr2
88
71
69
[FeCl2(dcpe)]
tBuLi
tBuLi + AlBr3
tBuLi + ZnBr2
c
c
77
From optimization studies (Table 1) it was clear that the
barrier to success lay with the transfer of the boryl group from
a
b
tBuBpin produced as coproduct, observed by GC-MS. By GC
n
c
d
(dodecane standard). 20 mol % with respect to nBuBr. From 99.99%
purity FeCl2. 6 mol % [Fe].
B2pin2 to the iron center. Initial attempts at coupling BuBr
with B2pin2, activated with KF, KOtBu, or NEt3 in the presence
of MgBr2 (20 mol %), gave little or none of the desired
product. Alkyl anions have been shown to be useful activating
agents in the iron-catalyzed Suzuki coupling of arylboronic
pinacol esters,8 and this approach proved fruitful here,
e
t
particularly when BuLi was exploited in the presence of
Received: August 21, 2014
Published: October 22, 2014
cocatalytic MgBr2 (entry 5).
© 2014 American Chemical Society
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Communication
a
Surprisingly, an increase in yield was observed in the absence
of added ligand (entry 7). Indeed, most of the P- or N-based
ligands we surveyed either hindered the catalysis or gave no
improvement in yield in comparison to “coligand-free”
conditions (see Table S1 in the Supporting Information).9
Only xantphos (4,5-bis(diphenylphosphino)-9,9-dimethylxan-
thene) and dcpe (1,2-bis(dicyclohexylphosphino)ethane) gave
higher yields (entries 8−10) than the phosphine-free system.
Table 2. Borylation of Alkyl, Benzyl, Allyl, and Aryl Halides
t
Both iron and BuLi (entries 11 and 12) were found to be
essential for the reaction, while an iron precatalyst made from
high-purity FeCl2 gave the same result as that obtained with
reagent grade FeCl2. In the absence of MgBr2 the yield dropped
significantly (entry 14). Replacing MgBr2 with either AlBr3 or
ZnBr2 gave little or no improvement in activity in comparison
t
with BuLi alone.
Table 2 summarizes the borylation of a range of substrates.
Typically, with more reactive substrates (allyl, benzyl, and
secondary alkyl halides) we obtained higher yields under
coligand-free conditions in comparison to those when
[FeCl2(dcpe)] was used, whereas with primary alkyl halides,
better activity was seen in the presence of the phosphine (see
Table S2 (Supporting Information) for full data).9 Gratifyingly
we obtained some, albeit modest, activity with aryl bromides, a
class of substrate that can prove challenging for iron catalysis.
Here the best precatalyst proved to be [FeCl2(dppe)].
Next we turned our attention to garnering mechanistic
insights, starting first with identifying the activated borylating
reagent. The reaction of B2pin2 with tBuLi in THF (Scheme 2)
gave a solution of a compound we assign as the borate ion
Li[B2pin2(tBu)] (1).
The solution of compound 1 showed two peaks in its 11B
NMR spectrum, a broad peak at δ 39.1 and a sharper peak at δ
6.4 similar to those observed previously for the related anion
[B2pin2(OMe)]− (δ 35.0 and 5.9).10 After the solvent was
removed, the solubility of the isolated solid 1 was poor. Despite
n
this, its reaction with BuBr, catalyzed by [FeCl2(dcpe)], still
n
gave BuBpin in 85% yield, strongly suggesting that 1 is the
borylating species. In effect, 1 behaves as a “masked” boryl
anion stabilized by coordination to an alkylboronic ester.11
As we previously observed in iron-catalyzed Suzuki coupling
reactions, phosphine-free precatalysts gave black, heteroge-
neous reaction mixtures.8b In contrast, the reaction of BuBr
n
with 1 catalyzed by [FeCl2(dcpe)] in THF gave a pale yellow,
homogeneous solution, allowing us to undertake initial-rate
kinetic studies. These were performed at 5 °C unless specified
otherwise. The initial rate of the reaction was found to be
independent of [1] over the range investigated,9 indicating that
1 was not involved in the rate-limiting step. For a reaction run
at 2.5 mM precatalyst concentration we observed no turnover
with an [MgBr2]0 = 8.3 mM. However, by [MgBr2]0 = 12.5 mM
the rate rose significantly, after which point further addition of
MgBr2 led to only a slight increase in rate. We have yet to
ascertain the role(s) played by the MgBr2, but it is interesting to
note that a nontrivial dependence on [MgBr2] was also
observed in Fe-catalyzed Suzuki coupling.8b
The initial rate showed an approximately first order
dependence on the concentration of the precatalyst,
[FeCl2(dcpe)]. Adding extra dcpe proved to be hugely
deleterious to the reaction, so much so that we needed to
increase the temperature of the reaction to 30 °C and double
the concentration of iron precatalyst in order to be able to
record meaningful rates. Under these conditions, the addition
of 0.5 equiv of dcpe led to an approximately 40-fold decrease in
a
t
Conditions: THF solution of B2pin2 (2.8 mmol) and BuLi (2.8
mmol) added to a THF solution of RX (2 mmol), MgBr2 (0.4 mmol),
and iron precatalyst (3 mol %, unless otherwise indicated), stirred at
b
room temperature for 1 h. Isolated yield, unless otherwise stated.
c
d
Determined by GC (dodecane internal standard). Determined by
e
1H NMR (1,3,5-(MeO)3C6H3 internal standard). 40 °C, 5 mol % Fe.
initial rate, beyond which point an approximately inverse first-
order dependence on [dcpe] was observed. A previously
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Scheme 2
observed inverse first-order dependence of rate on diphosphine
concentration in a related iron-catalyzed Suzuki coupling8b was
attributed to a pre-equilibrium between a stable bis-
diphosphine complex and a reactive mono-diphosphine species
immediately prior to the rate-determining step: the oxidation of
the latter species by the alkyl halide substrate. Here the effect of
added phosphine is far more pronounced and may indicate that
the active species is in fact diphosphine-free. In this scenario,
the phosphine would presumably stabilize resting state species
and thus prevent catalyst degradation: much the same role as
we previously proposed for chelating diamine ligands in iron-
catalyzed Kumada cross-coupling reactions.12
While it might be presumed that the reactions proceed via
the formation of iron boryl intermediates, we wished to
examine whether such species could indeed be formed under
catalytically relevant conditions. Under phosphine-free con-
ditions, the reaction of FeBr2 with excess 1 at room
temperature led to the immediate formation of a black
suspension.13 Although yellow to red homogeneous solutions
could be obtained at −78 °C on varying the B:Fe ratio from 3:1
through to 5:1, these species underwent rapid decomposition
on slight warming. So far we have not been able to isolate any
species from these reactions due to their extreme thermal
sensitivity; therefore, we focused instead on the equivalent
reactions of 1 with Fe phosphine complexes. The reaction of
[FeCl2(dpbz)2] (dpbz = 1,2-bis(diphenylphospino)benzene)
with 1 led to a rapid change from a yellow suspension to a deep
red solution, and we were able to isolate the iron(I) boryl
complex 2 in good yield (Scheme 3).
Figure 1. (top) X-ray structure of 2, with H atoms and C atoms except
for the ipso-C atoms of Ph residues omitted. Ellipsoids were set at 50%
probability. (bottom left) X-band EPR spectrum (THF, 140 K) of 2.
(bottom right) Calculated SOMO (isovalue 0.05 (electron/
bohr3)1/2) of low-spin 2.9
aryl) complexes,8b,12,14 presumably as a result of superhyperfine
coupling to 31P and both superhyperfine and quadrupolar
coupling to 10,11B. A density functional theory (B3LYP-D2)9
analysis of the ground-state structure of 2 gave a geometry and
electronic structure consistent with low-spin Fe(I) character
(Figure 1, bottom right). The Mulliken spin density
corresponding to the unpaired electron is located primarily
on the Fe atom (86.7%), with only very small contributions
from the ligating P and B atoms and the other ligand atoms.
Unsurprisingly, in view of the highly deleterious effect on the
rate of reaction of having >1 diphosphine ligand present in the
catalytic reaction, complex 2 showed poor activity as a catalyst
Scheme 3. Formation of an Fe(I) Boryl Complex
n
n
in the coupling of BuBr with 1, giving only 16% of BuBpin
after 16 h. This suggests that 2 is not an active catalyst but
rather that it slowly converts to an active species. This
presumably occurs on reaction with 1, since complex 2 showed
n
no reaction with a stoichiometric amount of BuBr in the
absence of 1 after 16 h.
In summary, the iron-catalyzed borylation of a range of alkyl,
allyl, benzyl, and aryl halides can be achieved. Preliminary
mechanistic investigations indicate that overcoordination by
chelating diphosphines slows the rate enormously. Conversely,
the stabilization provided by phosphine ligation allows the
isolation of a unique iron(I) boryl complex, the formation of
which shows that the activated borate 1 is sufficiently reducing
to be able to access oxidation states below Fe(II), adding to the
range of nucleophiles that yield Fe(I) under catalytically
relevant conditions.17 We are currently exploring both the
scope of the reaction and the mechanism in detail.
The single-crystal X-ray structure of 2 is shown in Figure 1
(top). The gross structure is very similar to those of other Fe(I)
complexes we have reported of the type [FeX(PP)2], where X =
aryl, halide and PP = dpbz, dppe.14 To the best of our
knowledge, this is both the first example of a boryl ligand on an
Fe(I) center (the vast majority of Fe boryl complexes contain
Fe(II))15 and the first example of an iron boryl species
supported solely by phosphine ligands. The Fe−B bond length
(2.065(3) Å) is similar to those at the longer end of the range
reported for iron(II) boryl complexes.15
Complex 2 is paramagnetic (μeff = 1.73 μB, Evans method,
ASSOCIATED CONTENT
THF, room temperature),16 consistent with an S = /2 spin
1
■
S
* Supporting Information
state, and is NMR silent. The X-band EPR spectrum of
complex 2 (Figure 1, bottom left) is significantly more
broadened and lacking in resolved hyperfine structure in
comparison to the spectra of related [FeX(PP)2] (X = halide,
Text, figures, tables, and CIF and xyz files giving experimental
details, spectroscopic data, and DFT calculations. This material
is available free of charge via the Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
Notes
The authors declare no competing financial interest.
■
ACKNOWLEDGMENTS
■
We thank the EPSRC for funding from the Bristol Chemical
Synthesis Centre for Doctoral Training (D.R.P.) and for
postdoctoral support (P.B.B., E.C.) and Dr. Natalie Fey and
Joshua Nunn for theory guidance and discussions.
REFERENCES
■
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