Iron-catalyzed aromatic amination for nonsymmetrical triarylamine synthesis

Article abstract of DOI:10.1021/ja309845k

Novel iron-catalyzed amination reactions of various aryl bromides have been developed for the synthesis of diaryl- and triarylamines. The key to the success of this protocol is the use of in situ generated magnesium amides in the presence of a lithium halide, which dramatically increases the product yield. The present method is simple and free of precious and expensive metals and ligands, thus providing a facile route to triarylamines, a recurrent core unit in organic electronic materials as well as pharmaceuticals.

Full text of DOI:10.1021/ja309845k

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Communication
Iron-Catalyzed Aromatic Amination for
Nonsymmetrical Triarylamine Synthesis
Takuji Hatakeyama, Ryuji Imayoshi, Yuya Yoshimoto, Sujit Kumar Ghorai, Masayoshi
Jin, Hikaru Takaya, Kazuhiro Norisuye, Yoshiki Sohrin, and Masaharu Nakamura
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/ja309845k • Publication Date (Web): 26 Nov 2012
Downloaded from http://pubs.acs.org on November 30, 2012
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Iron-Catalyzed Aromatic Amination for Nonsymmetrical
Triarylamine Synthesis
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Takuji Hatakeyama,†,‡ Ryuji Imayoshi,† Yuya Yoshimoto,† Sujit K. Ghorai,† Masayoshi Jin,†,§
Hikaru Takaya†, Kazuhiro Norisuye,† Yoshiki Sohrin,† and Masaharu Nakamura*,†
†International Research Center for Elements Science (IRCELS), Institute for Chemical Research (ICR), Kyoto University, Uji, Kyoto,
611-0011, Japan, ‡PRESTO, Japan Science and Technology Agency (JST), 5, Sanbancho, Chiyoda-ku, Tokyo, 102-0075, Japan
Supporting Information Placeholder
Scheme 1. Iron-catalyzed amination reaction between p-
bromoanisole 1 and magnesium diphenylamide 2
ABSTRACT: Novel iron-catalyzed amination reactions of various
aryl bromides have been developed for the synthesis of diaryl- and
triarylamines. The key to the success of this protocol is the use of in
situ generated magnesium amides in the presence of a lithium hal-
ide, which dramatically increases the product yield. The present
method is simple and free of precious and expensive metals and
ligands, thus providing a facile route to triarylamines, a recurrent
core unit in organic electronic materials as well as pharmaceuticals.
catalyst (X mol %)
additive (Y equiv)
Ph
Ph
Ph
+
Br
OMe
N
MgBr
N
OMe
OMe
xylene, 140 ºC, time Ph
3
1
(1.0 equiv)
2
(2.0 equiv)
+
+
OMe
MeO
4
5
Table 1. Screening of catalysts and additivesa
Transition-metal-catalyzed aromatic amination is widely used for
the synthesis of arylamines, which are of particular interest in the
yield (%)b
catalyst
(X mol%)
additive
(Y equiv)
recovery
of 1 (%)b
1 2
,
entry
time (h)
fields of organic electronics and bioactive compounds. Despite
recent improvements to Pd- and Cu-catalyzed amination method-
ologies such as the Buchwald–Hartwig and catalytic Ullmann reac-
3
4
0
0
0
0
0
0
4
0
4
4
3
0
5
1
2
3
24
24
12
24
12
48
48
48
48
48
48
48
10
26
51
95
>99
99
6
0
0
0
0
0
0
0
0
0
6
8
0
89
67
41
0
FeCl2 (5.0)
FeCl2 (5.0)
FeCl2 (5.0)
none
LiBr (0.2)
LiBr (2.0)
3
tions, new methods that do not require hazardous and expensive
transition metals and ligands are highly desired for the efficient
production of functional arylamines. Although considerable effort
has been devoted to the development of iron-catalyzed amination
4
5
0
FeCl2 (5.0)
FeCl2 (0.5)
PdCl2 (0.5)
CuCl2 (0.5)
CoCl2 (0.5)
NiCl2 (0.5)
Ni(acac)2 (0.5)
LiBr (4.0)
LiBr (4.0)
LiBr (4.0)
LiBr (4.0)
LiBr (4.0)
LiBr (4.0)
LiBr (4.0)
0
6
80
92
47
0
7
2
4
reactions in the last decade, they have limited substrate scope and
8
27
88
80
8
5
6
are unsuited for the synthesis of triarylamines, , which are among
9
1
the most prevailing hole-transport materials. In addition, Buch-
10
11
0
90
Ni(acac)2 (0.0005) LiBr (4.0)
wald and Bolm reported that the product yields of the reported
iron-catalyzed amination reactions are sensitive even to trace quan-
tities of copper contaminants, especially in the presence of N,N'-
aReactions were carried out on a 1.0 mmol scale. The yield was de-
termined by GC analysis using undecane as an internal standard.
b
7
dimethylethylenediamine (DMEDA). Hence, further investiga-
tion of suitable routes to triarylamines is needed from synthetic and
mechanistic perspectives. Herein, we report a facile and environ-
mentally benign method based on iron-catalyzed aromatic amina-
tion for synthesizing diaryl- and triarylamines and provide mecha-
nistic insights obtained through experimental and computational
studies on the iron amide species.
screening of catalyst systems based on iron and other transition
metals. The reaction between 1 and 2 in the presence of 5 mol %
FeCl2 gave the desired product 3 in 10% yield (entry 1), while the
reaction between 1 and diphenylamine in the presence of conven-
tional inorganic bases (K3PO4, Cs2CO3, NaHCO3, t-BuOK) did not
give any coupling product. The addition of LiBr accelerated the
reaction and the optimum yield (99%) was achieved when using
Since the standard conditions for Pd- or Cu-catalyzed aromatic
amination3 were not effective for iron catalysis, our study began
with an extensive screening of bases and additives. We eventually
found that the combination of a Grignard reagent (base) and a
lithium bromide (additive) dramatically promoted the amination
9
4.0 equiv of LiBr (entries 2–4). The increased yield is probably
due to the deaggregation of magnesium amide by the lithium salt to
facilitate transmetallation of the amide ligand from magnesium to
10
iron. Notably, magnesium diphenylamide, prepared from lithium
8
of aryl bromides with arylamines. The reaction between p-
diphenylamide and MgBr2, gave good yield (95%), while lithium
bromoanisole 1 and magnesium diphenylamide 2, prepared in situ
from diphenylamine and an ethyl Grignard reagent, was carried out
in xylene at 140 °C for 12–48 h, using a variety of catalysts and ad-
ditives (Scheme 1). Table 1 summarizes the results of this initial
diphenylamide gave a very poor yield (2%) under the same condi-
11
tions. Complete conversion could be achieved even with 0.5
12
mol % FeCl2 when the reaction was done in 48 h (entry 5).
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To clarify the effects of the metal contaminants, the iron salts
contaminant in FeCl2 was determined to be 12.9 ppm by the above
14
mentioned analysis, we examined the use of 5 × 10–4 mol %
Ni(acac)2 (1000 ppm of 0.5 mol %) as the catalyst to confirm the
low reactivity, and hence, concluded that nickel contamination
does not play an important role in the present iron-catalyzed ami-
nation reaction (entry 11).
were analyzed by inductively coupled plasma-mass spectrometry
and atomic emission spectroscopy (ICP-MS and ICP-AES). Since
ppm-order amounts of Pd, Cu, Co and Ni were found in some iron
salts, we performed the amination reaction in the presence of these
transition-metal catalysts. As in entries 6–8, PdCl2, CuCl2, and
CoCl2 showed poor catalytic activities under the same reaction
Table 2 summarizes the substrate scope of the aromatic amina-
tion. As shown in entries 1–10, a variety of aryl- and heteroaryl
bromides could be coupled with diarylamines to give the corre-
sponding triarylamines in good yields. Although anilines did not
participate in the reaction, a protected aniline, N-(trimethylsilyl)
aniline, coupled with the aryl bromides to give, upon hydrolysis, the
13
conditions. As reported by Yang, NiCl2 and Ni(acac)2 showed
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catalytic activity comparable to that of the iron catalysts but gave
lower product yields owing to the competing homocoupling of p-
bromoanisole (entries 9 and 10). Since the amount of nickel
Table 2. Substrate scopea
15
corresponding diarylamines in excellent yields (entries 11–14).
entry
amine
aryl halide
product
yield (%)b
The reactions with N-(trimethylsilyl)aniline proceeded more
smoothly in dibutyl ether than in xylene. As shown in entries 15
and 16, the hole-transport material, N,N'-diphenyl-N,N'-di(m-
tolyl)benzidine (TPD), and its precursor could be prepared from
4,4'-dibromo-1,1'-biphenyl in 82% and 87% yields, respectively.
Aryl bromides possessing an ester or nitrile group underwent the
addition of magnesium amides to the electrophilic functional
groups and desired amination products were not obtained. Ketone
and nitro groups were not tolerated under the reaction conditions
and gave complex mixtures (data not shown). The relatively nar-
row functional-group compatibility compared to the standard Pd-
and Cu-catalyzed aminations5,6 is due to the high reactivity of the
magnesium amides and further effort to find suitable combinations
of a base and a neutral amine is needed to overcome this limitation.
1
2
3
4
5
92 (R = Me)
Ph
Ph
Ph
Ph
90 (R = OMe)
88 (R = NMe2)
59 (R = Cl)
Br
Br
R
N
N
H
H
N
R
77 (R = F)
Ph
Ph
Ph
N
Ph
6
90
82
Ph
Ph
Ph
N
Ph
Br
Br
Br
7
8
9
N
N
N
H
H
H
N
N
Ph
Ph
Ph
N
Ph
S
S
61
Scheme 2. Preparation of iron(II) diamide complex A and the
stoichiometric reaction
p-Tol
p-Tol
p-Tol
96
N
p-Tol
Me3Si Ph
NaN(SiMe3)2
(2.0 equiv)
FeCl2
(1.0 equiv)
N
N FeII FeII
N
Ph
Ph
SiMe3
Ph
p-FC6H4
p-FC6H4
N
H
10
82
Br
Br
OMe
OMe
N
N
H
N
OMe
THF, rt, 3 h
rt, 15 h
Me3Si
Me3Si
Ph
Ph
Ph
N
H
Ph SiMe3
(2.0 equiv)
A
25% yield
Ph
11c
N
N
H
H
96
OMe
Me3Si
Ph
+
A
Br
OMe
N
H
OMe
dibutyl ether
140 ºC, Y h
Ph
N
H
Ph
1 (0.40 mmol)
(X mmol)
Br
Br
12c
76
97
X, Y = 0.10, 1 47% yield
X, Y = 0.10, 6 53% yield
X, Y = 0.20, 1 81% yield
X, Y = 0.20, 6 93% yield
Me3Si
Me
Me
Ph
H
Ph
N
13c
14c
N
N
H
H
Selected bond lengths
Fe1–N2 1.9147(18) Å
Fe1–N1 2.0702(18) Å
Fe1–N1' 2.0348(16) Å
Fe1–Fe1' 2.7408(7) Å
Me3Si
Si1'
C1
Si2'
Ph
H
Ph
C10
Fe1
N1
Selected angles
Br
N
N1'
98
N2
N2–Fe1–N1 130.88(7)º
N2–Fe1–N1' 132.89(8)º
N1–Fe1–N1' 96.23(6)º
Fe1–N1–Fe1' 83.77(6)º
Fe1–N2–C1 114.04(13)º
Fe1–N2–Si2 128.45(10)º
C1–N2–Si2 117.46(14)º
C10–N1–Si1 115.22(13)º
Fe1'
N
N
Me3Si
N2'
C10'
m-Tol
m-Tol
N
Ph
Si2
m-Tol
C1'
N
15c, d
82
Si1
Br
Br
Br
Br
N
N
H
H
Ph
2
Ph
2
Ph
H
Ph
N
H
Ph
16c, d
N
Figure 1. ORTEP drawing of A. Thermal ellipsoids are shown
at 50% probability; hydrogen atoms are omitted for clarity.
87
2
Me3Si
2
aReactions were carried out on a 1.00 mmol scale according to the
To gain further insights into the mechanism, we prepared an
16
b
procedure described in Table 1 (entry 4), unless otherwise noted. I-
iron(II) diamide complex A according to Power’s method and
c
d
solated yield. The reaction was carried out in dibutyl ether. The reac-
tion was carried out on a 0.50 mmol scale using 4.0 equiv of amine.
conducted a stoichiometric reaction (Scheme 2). Deprotonation of
N-(trimethylsilyl)aniline with sodium bis(trimethylsilyl)amide
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(NaHMDS), followed by treatment with FeCl2, gave a dimer com-
plex of iron(II) diamide A in 25% yield. X-ray crystallography anal-
kcal/mol higher in energy than dimer A, undergoes oxidative addi-
tion with bromobenzene (Ph–Br) through the formation of σ-
complex (C) to give the iron(IV) intermediate D. The overall acti-
vation energy from A to D via TSCD is 26.7 kcal/mol, which is in fair
agreement with the experimental finding that the reaction proceeds
smoothly at 140 °C. Although oxidative addition is an endothermic
process, rapid reductive elimination of the coupling product from
ysis showed that A was dimeric, with each trigonal-planar iron
16
bound to one terminal and two bridging amide groups (Figure 1).
Aromatic amination of 1 in Bu2O at 140 °C for 6 h gave the desired
product in 53% and 93% yields in the presence of 0.25 and 0.50
equiv of A, respectively. This result clearly show that the iron(II)
diamide can be a reactive intermediate in which one of two amide
groups (per iron) takes part in the amination.
D gives the stable σ-complex E, which can drive the C–N coupling
reaction forward. Dissociation of the coupling product (E to F) and
subsequent transmetalation with magnesium amide regenerates the
iron diamide B to complete the catalytic cycle, or alternatively, the
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Ar2
Br
Br–Ar2
FeIV
Ar1
FeIICl2
R
N
R
N
Ar1
22
dimer formation from F to G and the transmetalation regenerate
+
2 Ar1RNMgBr!LiBr
the starting dimer A, the experimentally determined reactive inter-
mediate.
Ar1
N
R
Ar1
N
R
R
Ar2
R = aryl or SiMe3
FeII
N
In summary, we have developed an efficient iron-catalyzed aro-
matic amination between diaryl- or arylsilyl amines and aryl bro-
mides, which affords high product yields and selectivity, in the
presence of a simple catalyst system. The key to the success of the
reaction is the combined use of magnesium amide and lithium salt
additives, which promotes the catalyst turnover. A stoichiometric
reaction involving a newly synthesized iron(II) diamide complex
and DFT studies on the reaction pathway reveal that the present
reaction proceeds via a nonconventional Fe(II)–Fe(IV) mecha-
nism. These mechanistic insights will aid the design of new carbon–
nitrogen and other carbon–heteroatom bond formations in the
future.
Ar1
R
Ar1
Ar1
N
R
Ar1
R
N
FeII Br
MgBr2!LiBr
1/2 N FeII FeII
N
Ar1
R
N
R
Ar1RNMgBr!LiBr
Ar1
A
Figure 2. Possible catalytic cycle of iron-catalyzed aromatic
amination.
Figure 2 shows a plausible mechanism on the basis of the stoichi-
ometric studies. The precatalyst, FeCl2, reacts with 2.0 equiv of
magnesium amide to form monomeric and dimeric iron(II) dia-
17
,18
ASSOCIATED CONTENT
mide complexes, which are in monomer–dimer equilibrium.
The coordinatively unsaturated monomer may undergo oxidative
addition with an aryl bromide to form a formal iron(IV) intermedi-
ate. Successive reductive elimination of the coupling product af-
fords iron(II) monoamide complex. Regeneration of the active
species completes the catalytic cycle via the LiBr-assisted
transmetallation with magnesium amide.
Supporting Information. Experimental procedure, characterization,
photophysical data, electrochemical data, crystallographic data, and a
CIF file for the products, as well as computational method and data.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Me3Si Ph
Ph
Br
Corresponding Author
masaharu@scl.kyoto-u.ac.jp
N
FeII FeII
N
SiMe3
Ph
Ph
+ Ph–Br
Ph
Ph
1/2
FeII
N
Ph
Ph
N
N
N
FeII
N
N
SiMe3
Me3Si
Me3Si
SiMe3
Me3Si
Ph SiMe3
A (0)
Present Address
C (+12.5)
B (+5.4)
§Process Technology Research Laboratories, Pharmaceutical Technol-
ogy Division, Daiichi Sankyo Co., Ltd., 1-12-1, Shinomiya, Hiratsuka,
Kanagawa 254-0014, Japan
!G‡ = +14.2
2.20
Ph Br
Br
Br
‡
‡
Ph
Ph
!G‡ = +8.7
Ph
Fe
FeIV
Ph
Ph
Fe
Ph
N
Ph
1.89
N 1.95
N
SiMe3
N
N
Ph
N
SiMe3
SiMe3
SiMe3
ACKNOWLEDGMENT
SiMe3
SiMe3
TSCD (+26.7)
TSDE (+19.9)
D (+11.2)
This research was supported by the Japan Society for the Promotion of
Science (JSPS) through the “Funding Program for Next Generation
World-Leading Researchers (NEXT Program),” initiated by the Coun-
cil for Science and Technology Policy (CSTP) and the Japan Science
and Technology Agency (JST), the Core Research for Evolutional
Science and Technology (CREST) Program. We are grateful to Profes-
sor Kazuyuki Tatsumi (Nagoya University), Associate Professor Ya-
suhiro Ohki (Nagoya University), Mr. Takayoshi Hashimoto (Nagoya
University), and Mr. Genki Kawase (Nagoya University) for their
experimental guidance on the synthesis of iron amides. We also thank
Mr. Sigma Hashimoto (Kyoto University) and Mr. Yoshihiro Okada
(Kyoto University) for the experimental support. The synchrotron X-
ray absorption measurements were performed at BL14B2 (2011B1945,
Br
FeII
Ph
2.34
– Ph2NSiMe3
Br
FeII FeII
Br
Ph
Ph
SiMe3
Ph
Ph N
Me3Si
FeII
1/2
N
Br
N
N
N
Ph
SiMe3
E (–11.8)
Me3Si
Me3Si
F (–8.3)
G (–28.4)
Figure 3. Reaction pathways for oxidative addition and reductive
elimination. Gibbs free energies (ΔG, calculated at the B3LYP/6-
31G(d) level) relative to A are given in kcal/mol in parentheses.
19 20
,
To evaluate the nonconventional Fe(II)–Fe(IV) mechanism,
we performed a set of density functional theory (DFT) calculations
and have located an energetically reasonable reaction coordinates,
21
starting from monomer B (Figure 3). Monomer B, which is 5.4
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2012A1595) and BL27SU (2011B1418, 2012A1636) in SPring-8 with
the approval of JASRI.
REFERENCES
5
6
(10) Lithium chloride deaggregates TMPMgCl resulting in the for-
7
8
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(16) Bond lengths and angles are similar to those reported for the re-
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1599–1626. (c) Hartwig, J. F. Synlett 2006, 9, 1283–1294. (d) Surry, D. S.;
Buchwald, S. L. Angew. Chem., Int. Ed. 2008, 47, 6338–6361. (e) Evano, G.;
Blanchard, N.; Toumi, M. Chem. Rev. 2008, 108, 3054–3131. (f) Monnier,
F.; Taillefer, M. Angew. Chem., Int. Ed. 2009, 48, 6954–6971. (g) Surry, D.
S.; Buchwald, S. L. Chem. Sci. 2010, 1, 13–31. (h) Sadig, J. E. R.; Willis, M.
C. Synthesis 2011, 1–22. (i) Surry, D. S.; Buchwald, S. L. Chem. Sci. 2011, 2,
27–50. (j) Rauws, T. R. M.; Maes B. U. W. Chem. Soc. Rev. 2012, 41, 2463–
2497.
(4) Review: (a) Correa, A.; Mancheño, O. G.; Bolm, C. Chem. Soc. Rev.
2008, 37, 1108–1280. Recent reports: (b) Nakamura, Y.; Ilies, L.; Naka-
mura, E. Org. Lett. 2011, 13, 5998–6001. (c) Liu, X. Zhang, S. Synlett. 2011,
8, 1137–1142.
(5) Selected examples for triarylamine synthesis based on palladium ca-
talysis: (a) Thayumanavan, S.; Barlow, S.; Marder, S. R. Chem. Mater. 1997,
9, 3231–3235. (b) Louie, J.; Hartwig, J. F. J. Am. Chem. Soc. 1997, 119,
11695–11696. (c) Yamamoto, T.; Nishiyama, M.; Koie, Y. Tetrahedron Lett.
1998, 39, 2367–2370. (d) Harris, M. C.; Buchwald, S. L. J. Org. Chem.
2000, 65, 5327–5333. (e) Hooper, M. W.; Utsunomiya, M.; Hartwig, J. F. J.
Org. Chem. 2003, 68, 2861–2873. (f) Surry, D. S.; Buchwald, S. L. J. Am.
Chem. Soc. 2007, 129, 10354–10355. (h) Suzuki, K.; Hori, Y.; Kobayashi, T.
Adv. Synth. Catal. 2008, 350, 652–656. (i) Monguchi, Y.; Kitamoto, K.;
Ikawa, T.; Maegawa, T.; Sajiki, H. Adv. Synth. Catal. 2008, 350, 2767–2777.
(j) Hirai, Y.; Uozumi, Y. Chem. Asian J. 2010, 5, 1788–1795.
(6) Selected examples for triarylamine synthesis based on copper cataly-
sis: (a) Goodbrand, H. B.; Hu, N.-X. J. Org. Chem. 1999, 64, 670–674. (b)
Gujadhur, R. K.; Bates, C. G.; Venkataraman, D. Org. Lett. 2001, 3, 4315–
4317. (c) Kelkar, A. A.; Patil, N. M.; Chaudhari, R. V. Tetrahedron Lett.
2002, 43, 7143–7146. (d) Patil, N. M.; Kelkar, A. A.; Chaudhari, R. V. J.
Mol. Catal. A 2004, 223, 45–50. (e) Liu, Y.-H.; Chen, C.; Yang, L.-M. Tet-
rahedron Lett. 2006, 47, 9275–9278. (f) Zhao, Y.; Wang, Y.; Sun, H.; Li, L.;
Zhang, H. Chem. Commun. 2007, 3186–3188. (g) Nandurkar, N. S.;
Bhanushali, M. J.; Bhor, M. D.; Bhanage, B. M. Tetrahedron Lett. 2007, 48,
6573–6576. (h) Sawant, S. K.; Gaikwad, G. A.; Sawant, V. A.; Yamgar, B.
A.; Chavan, S. S. Inorg. Chem. Commun. 2009, 12, 632–635. (i) Tlili, A.;
Monnier, F.; Taillefer, M. Chem. Commun. 2012, 48, 6408–6410.
(7) Buchwald, S. L.; Bolm, C. Angew. Chem., Int. Ed. 2009, 48, 5586–
5587 and references cited therein.
(17) The dimer form is stable in the solid and solution states. See the
supporting information and reference 16.
(18) Preliminary synchrotron X-ray absorption measurements have
shown that the oxidation state of the iron diamides was not lower than +II
state. Details will be reported in a separate paper.
(19) The Fe(II)–Fe(III) mechanism was proposed for iron-catalyzed
cross coupling of alkyl halides. (a) Noda, D.; Sunada, Y.; Hatakeyama, T.;
Nakamura, M.; Nagashima, H. J. Am. Chem. Soc. 2009, 131, 6078–6079.
(b) Hatakeyama, T.; Hashimoto, T.; Kondo, Y.; Fujiwara, Y.; Seike, H.;
Takaya, H.; Tamada, Y.; Ono, T.; Nakamura, M. J. Am. Chem. Soc. 2010,
132, 10674–10676. (c) Kawamura, S.; Ishizuka, K.; Takaya. H.; Nakamura,
M. Chem. Commun. 2010, 46, 6054–6056. (d) Hatakeyama, T.; Okada, Y.;
Yoshimoto, Y.; Nakamura, M. Angew. Chem., Int. Ed. 2011, 50, 10973–
10976. (d) Hatakeyama, T.; Fujiwara, Y.; Okada, Y.; Itoh, T.; Hashimoto,
T.; Kawamura, S.; Ogata, K.; Takaya, H.; Nakamura, M. Chem. Lett. 2011,
40, 1030–1032. (e) Ghorai, S. K.; Jin, M.; Hatakeyama, T.; Nakamura, M.
Org. Lett. 2012, 14, 1066–1069. (f) Hatakeyama, T.; Hashimoto, T.;
Kathriarachchi, K. K. A. D. S.; Zenmyo, T.; Seike, H.; Nakamura, M. Angew.
Chem., Int. Ed. 2012, 51, 8834–8837.
(20) The Fe(II)–Fe(IV) mechanism was proposed for iron-catalyzed
biaryl coupling. (a) Hatakeyama, T.; Nakamura, M. J. Am. Chem. Soc. 2007,
129, 9844–9845. (b) Hatakeyama, T.; Hashimoto, S.; Ishizuka, K.; Naka-
mura, M. J. Am. Chem. Soc. 2009, 131, 11949–11963.
(21) The reaction coordinate was investigated for the high-spin state
(A: S = 4, others: S = 2) because A and B in the high-spin state are stable by
more than 20 kcal/mol as compared to those in the low- and intermediate-
spin states. See the supporting information for details.
(8 ) Lithium salts accelerate the iron-catalyzed cross-coupling of alkenyl
bromides and triflates with alkynyl Grignard reagents: Hatakeyama, T.;
Yoshimoto, Y; Toma, G.: Nakamura, M. Org. Lett. 2008, 10, 5541–5544.
(9) Other lithium salts (LiCl, LiI, LiOMe, LiOH) and NaBr also im-
proved the product yield but were not as effective as LiBr. See the support-
ing information for details.
(22) The nitrogen-bridged dimer was less stable by 1.9 kcal/mol
(Gibbs free energy) than G. See the supporting information for details.
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cat. FeCl2
LiBr
Ar
R
Ar
+
Ar'–Br
NMgBr
N Ar'
xylene or Bu2O
140 ºC
R
R = aryl or Me3Si
16 examples, 59–98% yield
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