Iron(III) amine-bis(phenolate) complexes as catalysts for the coupling of alkyl halides with aryl Grignard reagents

Article abstract of DOI:10.1039/b713647a

Catalytic cross-coupling of aryl Grignard reagents with primary and secondary alkyl halides bearing β-hydrogens is achieved using Fe(III) amine-bis(phenolate) halide complexes. The Royal Society of Chemistry.

Full text of DOI:10.1039/b713647a

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Iron(III) amine-bis(phenolate) complexes as catalysts for the coupling of
alkyl halides with aryl Grignard reagents{
Rajoshree Roy Chowdhury, Angela K. Crane, Candace Fowler, Philip Kwong and Christopher M. Kozak*
Received (in Cambridge, UK) 5th September 2007, Accepted 14th November 2007
First published as an Advance Article on the web 23rd November 2007
DOI: 10.1039/b713647a
Eight Fe(III) complexes were prepared by the dropwise addition
of a methanol solution of FeCl3 to a methanolic slurry of the
ligand at room temperature (eqn. 1). This dark blue solution was
neutralized using NEt3 and evaporated to dryness. Extraction into
toluene, filtration and removal of the solvent gave analytically pure
complexes in good yield.
Catalytic cross-coupling of aryl Grignard reagents with primary
and secondary alkyl halides bearing b-hydrogens is achieved
using Fe(III) amine-bis(phenolate) halide complexes.
Transition metal-catalyzed Grignard cross-coupling is an impor-
tant class of C–C bond forming reaction.1 Traditionally, Ni and
Pd complexes have been used to perform the Kumada–Corriu
coupling of alkyl Grignard reagents with alkyl or aryl halides.2–4
Related iron(III) chloride complexes possessing salen ligands have
recently been shown to be capable of cross-coupling alkyl
Grignards with aryl halides, as well as coupling aryl Grignards
with alkyl halides.5–7 Other iron complexes have shown activity in
the cross-coupling of both primary and secondary alkyl halides
with aryl Grignard reagents. The use of Fe(acac)3 shows good
activity towards the coupling of aryl Grignard reagents with alkyl
halides,8 as does FeCl3 in the presence of simple amines.9–11 Also,
cross-coupling can be catalyzed by phosphine, phosphite, arsine
and carbene ligands with FeCl3 or FeCl2.12 Lower oxidation state
iron compounds have also shown cross-coupling activity, including
the formally Fe(2II) complex [Li(tmeda)]2[Fe(C2H4)2], the ‘‘inor-
ganic Grignard’’ reagent [Fe(MgX)2] and the Fe(II) ‘ate’ complex
[Me4Fe][Li2(OEt2)2].13,14 Iron nanoparticles have also been pro-
posed as active catalysts for the coupling of aryl Grignard reagents
with alkyl halides.15 The use of FeCl3 directly in the above
reactions, or its use to generate an active catalyst in situ, is often
inconvenient on a large scale because it is highly hygroscopic, and
yields vary according to its purity and commercial origin.11
Although Fe(acac)3 is a more convenient, less hygroscopic starting
material, amine additives must be employed to achieve high
conversions and yields of cross-coupled products. An easy to use,
non-hygroscopic single component catalyst precursor is therefore
highly desirable. Herein, we report the synthesis of iron chloride
complexes of amine-bis(phenolate) ether ligands and their use in
the catalytic cross-coupling of aryl Grignard reagents with primary
and secondary alkyl halides.
(1)
The complexes have magnetic moments of 5.5 to 5.9 mB at room
temperature, consistent with high spin d5 configurations. MALDI
mass spectrometry using an anthracene matrix can be used to
characterize the iron complexes; compounds 1–8 all show
molecular ion peaks and characteristic fragment ions. Slow
evaporation of a solution of FeClL1 (1) in methanol gave crystals
suitable for X-ray diffraction.{ The structure of 1 is shown in
Fig. 2, along with selected bond lengths and angles. The
coordination geometry around the iron atom is distorted trigonal
bipyramidal. The metal is bonded to two phenolate oxygen atoms
and the furfuryl oxygen atom, which define the trigonal plane of
the bipyramid. The central nitrogen atom of the ligand and the
chloride ion occupy the apical sites. The Fe–O(2) and Fe–O(3)
distances of 1.854(2) and 1.850(2) s, respectively, for the phenolate
oxygen donors are similar to those observed in related trigonal
bipyramidal and square pyramidal iron(III) complexes possessing
diamine bis(phenolate) ligands.20,21 However, the Fe–Cl and Fe–N
bond distances of 2.2739(10) and 2.223(3) s, respectively, are
slightly shorter in 1. The iron atom is displaced 0.206 s above the
equatorial plane. The N–Fe–Cl angle of 165.69(8)u is considerably
The amine-bis(phenolate) ligands in Fig. 1 were prepared using
literature procedures by employing a Mannich condensation of the
corresponding phenol, amine and formaldehyde.16–19 Single
crystals of L1H2 were obtained from a saturated methanol
solution and were characterized by X-ray diffraction.{
Memorial University of Newfoundland, Department of Chemistry,
Centre for Green Chemistry and Catalysis, St. John’s, Newfoundland,
Canada A1B 3X7. E-mail: ckozak@mun.ca
{ Electronic supplementary information (ESI) available: Experimental
details, crystallographic data for L1H2 and 1, and characterization data
(GC and NMR) for the cross-coupled products. See DOI: 10.1039/
b713647a
Fig. 1 Ligand variationsemployed in the synthesis ofFe(III) precatalysts.
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Table 1 Cross-coupling of ArMgBr with alkyl halidesa
Yieldb
(%)
Entry ArMgBr
Alkyl halide
Product
1
Ar = para-tolyl Bromocyclohexane
99
2
3
4
5
6
7
Bromocyclohexanec
Bromocyclohexaned
Bromocyclohexanee
Chlorocyclohexane
Iodocyclohexane
0
0
0
0
0
80
99
50
48
99
50
Benzyl bromide
Fig. 2 The molecular structure (ORTEP) and numbering scheme for 1.
Ellipsoids are shown at 30% probability. Selected bond distances (s) and
angles (u): Fe1–O3 1.850(2), Fe1–O2 1.854(2), Fe1–O1 2.074(3), Fe1–N1
2.223(3), Fe1–Cl1 2.2739(10), O1–C29 1.452(5), O1–C26 1.468(5), O2–C7
1.346(4), O3–C19 1.352(4); O3–Fe1–O2 118.39(10), O3–Fe1–O1
119.00(11), O2–Fe1–O1 119.60(11), O3–Fe1–N1 87.62(10), O2–Fe1–N1
89.37(10), O1–Fe1–N1 75.79(10), O3–Fe1–Cl1 100.81(8), O2–Fe1–Cl1
96.60(8), O1–Fe1–Cl1 89.98(8), N1–Fe1–Cl1 165.69(8).
8
2-Bromobutane
2-Bromopentane
79
99
90
54
99
9
10
11
12
1-Bromooctane
1-Iodopropane
distorted from the ideal linear geometry; it is bent away from the
phenolate groups and directed toward the tetrahydrofurfuryl
fragment.
Ar = ortho-tolyl Bromocyclohexane
13
14
15
Chlorocyclohexane
Iodocyclohexane
Benzyl bromide
0
0
62
99
68
For the preliminary screening of catalyst performance, the
reaction shown in eqn. 2 was chosen. In addition to the desired
cross-coupled product, by-products may include the elimination
product (cyclohexene), the hydrodehalogenated product (cyclo-
hexane) and two possible homo-coupled products (dicyclohexane
and bitoluene).1 Initially, complexes 1 to 8 were examined for their
catalytic cross-coupling activity, but little variation was seen
among them, thus implying a negligible effect imposed by either
the aryl substituents or the pendant donor groups examined.
Iron(III) salen complexes displayed a similar behaviour, where
16
17
18
19
20
2-Bromobutane
2-Bromopentane
50
64
99
53
99
1-Bromooctane
t
ortho and para Bu-modified analogues showed essentially the
same activity as systems containing only hydrogen atoms in these
positions.5 For subsequent reaction optimization experiments,
complex 1 was employed.
1-Iodopropane
Ar = para-anisylf Bromocyclohexane
21
22
23
Chlorocyclohexane
Iodocyclohexane
Benzyl bromide
0
0
22
81
0
(2)
24
25
26
27
a
2-Bromobutane
2-Bromopentane
1-Bromooctane
1-Iodopropane
37
35
30
42
Several sets of reaction conditions were examined to determine
their effect on both the conversion to products and the selectivity
for cross-coupling. We found that adding the catalyst as a solution
in CH2Cl2 and removing the solvent under vacuum consistently
gave superior conversions and yields of products compared to
when it is added as a solid. This is consistent with what is observed
when [FeCl(salen)] complexes were used for this reaction.5 The
catalyst loading was maintained at 5.0 mol% throughout. The
solvent, temperature and amount of Grignard reagent used were
examined for their influence on the conversion and yield (Table 1).
Using diethyl ether and conducting the reaction at room
temperature gave an excellent yield of cross-coupled product B
Conditions: ArMgBr (4.0 mmol), alkyl halide (2.0 mmol), catalyst
b
1 (5.0 mol%), Et2O, 25 uC, 30 min. Yield determined by GC using
dodecane as the internal standard; average of 2 trials. Solvent used
was THF instead of Et2O. Reaction conducted at 0 uC. 2.0 mmol
of ArMgBr used. 0.5 M solution in THF.
c
d
e
f
(Table 1, entry 1). The use of THF (Table 1, entry 2) lead to a
lower yield, while conducting the reaction at 0 uC did not affect the
yield of the desired product (Table 1, entry 3). Decreasing the
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153 K, Z = 2, m(Mo-Ka) = 0.707 cm21, Dc = 1.117 g cm23, 13994
reflections measured, 6808 unique reflections (Rint = 0.019), R[I . 2s(I)] =
0.0600, wR2 = 0.1659. CCDC 659673.
Crystal data for 1: C29H41ClFeNO3, M = 542.95, black prism,
monoclinic, P21/n (#14), a = 9.7824(8), b = 25.0778(19), c = 12.3276(9) s,
b = 95.0780(19)u, V = 3012.4(4) s3, T = 153 K, Z = 4, m(Mo-Ka) =
6.160 cm21, Dc = 1.197 g cm23, 27790 reflections measured, 8185 unique
reflections (Rint = 0.049), R[I . 2s(I)] = 0.0836, wR2 = 0.2400. CCDC
659674.
For crystallographic data in CIF or other electronic format see DOI:
10.1039/b713647a. See the ESI for full experimental procedures and
characterization.{
Grignard reagent stoichiometry decreased the yield of the desired
cross-coupled product (Table 1, entry 4), but increasing the
amount of Grignard reagent was only found to generate more
biaryl product C. It has been proposed that excess Grignard is
required to reduce the Fe(III) precatalyst, thus generating the active
catalyst.7,11 During these initial screenings, the presence of
products D, E and F were only detected in trace amounts by
GC-MS.
Subsequently, substrate screening was performed using
the conditions shown in Table 1. Under these conditions,
conversion to the cross-coupled products of 4-MeC6H4MgBr,
2-MeC6H4MgBr and 4-MeOC6H4MgBr with bromocyclohexane
each gave 99% yields. Similarly high yields were observed using
iodocyclohexane with 4-MeC6H4MgBr and 2-MeC6H4MgBr
1 Metal-Catalyzed Cross-Coupling Reactions, ed. A. de Meijere and
F. Diederich, Wiley-VCH, Weinheim, 2004.
2 D. J. Cardenas, Angew. Chem., Int. Ed., 2003, 42, 384.
3 A. C. Frisch and M. Beller, Angew. Chem., Int. Ed., 2005, 44, 674.
4 M. R. Netherton and G. C. Fu, Adv. Synth. Catal., 2004, 346,
1525.
(Table 1, entries
6 and 14), but decreased slightly with
MeOC6H4MgBr (Table 1, entry 22). Chlorocyclohexane gave very
poor yields with all three Grignard reagents (Table 1, entries 5, 13
and 21). Acyclic alkyl halide reagents generally gave poorer yields
of cross-coupled products and also showed the highest yields of
biaryl products. Benzyl bromide only showed fair cross-coupling
activity with tolyl Grignards; no product was observed using
MeOC6H4MgBr. Also, using benzyl bromide as the alkyl source
generated significant yields of bibenzyl, a product of alkyl halide
coupling.
5 R. B. Bedford, D. W. Bruce, R. M. Frost, J. W. Goodby and M. Hird,
Chem. Commun., 2004, 2822.
6 A. Fu¨rstner and A. Leitner, Angew. Chem., Int. Ed., 2002, 41, 609.
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2002, 124, 13856.
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R. M. Frost and M. Hird, J. Org. Chem., 2006, 71, 1104.
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14 A. Fu¨rstner, H. Krause and C. W. Lehmann, Angew. Chem., Int. Ed.,
2006, 45, 440.
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M. Hird, Chem. Commun., 2006, 1398.
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Inorg. Chim. Acta, 2003, 345, 137.
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J. M. Lynam, A. C. Whitwood and C. E. Willans, Can. J. Chem., 2007,
submitted for publication.
In summary, new Fe(III) chloride complexes with amine-
bis(phenolate) ligands have been easily synthesized and show
excellent potential as catalysts for the cross-coupling of aryl
Grignard reagents with primary and secondary alkyl halides.
Further studies evaluating the scope and limitations of this
reaction with other aryl Grignard reagents are being pursued. For
example, functional group tolerance studies and reaction condition
optimization are under way.
We gratefully acknowledge Memorial University and the
NSERC of Canada for funding (C. M. K.) and Undergraduate
Student Research Awards (A. K. C. and P. K.). We thank Julie
Collins for crystallography and C-CART for assistance. P. K. also
thanks the Inorganic Chemistry Exchange (ICE) Program.
20 M. Velusamy, M. Palaniandavar, R. S. Gopalan and G. U. Kulkarni,
Inorg. Chem., 2003, 42, 8283.
Notes and references
{ Crystal data for L1H2: C29H43NO3, M = 453.66, colourless, prism,
21 P. Mialane, E. Anxaolabe´he`re-Mallart, G. Blondin, A. Nivorojkine,
J. Guilhem, L. Tchertanova, M. Cesario, N. Ravi, E. Bominaar,
J. J. Girerd and E. Munck, Inorg. Chim. Acta, 1997, 263, 367.
¯
triclinic, P1 (#2), a = 10.453(4), b = 11.703(4), c = 12.508(4) s,
a = 101.931(6), b = 107.410(5), c = 104.170(7)u, V = 1349.3(8) s3, T =
96 | Chem. Commun., 2008, 94–96
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