1030
Published on the web September 5, 2011
Kumada-Tamao-Corriu Coupling of Alkyl Halides Catalyzed
by an Iron-Bisphosphine Complex
Takuji Hatakeyama,1 Yu-ichi Fujiwara,1,2 Yoshihiro Okada,1,2 Takuma Itoh,1,2 Toru Hashimoto,1,2
Shintaro Kawamura,1,2 Kazuki Ogata,1,2 Hikaru Takaya,1 and Masaharu Nakamura*1
1International Research Center for Elements Science (IRCELS), Institute for Chemical Research (ICR),
Kyoto University, Uji, Kyoto 611-0011
2Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering,
Kyoto University, Nishikyo-ku, Kyoto 615-8530
(Received July 4, 2011; CL-110567; E-mail: masaharu@scl.kyoto-u.ac.jp)
t-Bu
t-Bu
An iron(II) chloride complex possessing
a sterically
t-Bu
t-Bu
demanding ortho-phenylene-tethered bisphosphine ligand shows
a high catalytic activity in the Kumada-Tamao-Corriu coupling
of nonactivated alkyl halides with aryl Grignard reagents.
Primary, secondary, and tertiary alkyl halides can participate as
an electrophilic coupling partner. A radical clock experiment
using (iodomethyl)cyclopropane exclusively gives the corre-
sponding ring-opening coupling product, suggesting intermedi-
acy of alkyl radical species.
FeCl2(H2O)4
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
P
P
P
P
EtOH
90 °C, 6 h
82% yield
Fe
Cl Cl
FeCl2(3,5-t-Bu2-SciOPP)
t-Bu
t-Bu
t-Bu
t-Bu
3,5-t-Bu2-SciOPP
Scheme 1. Synthesis of an iron complex.
Table 1. Screening of iron catalyst
Br
Transition-metal-catalyzed cross-coupling is one of the most
powerful tools in organic synthesis.1 After dormancy for
decades, iron has attracted renewed attention as a practical
coupling catalyst due to its economic and ecological advantages
over the other rare metal catalysts.2,3 Moreover, iron catalyst
displays characteristic reactivities and selectivities, which cannot
be easily attained by the prevalent Ni- and Pd-catalysts: several
research groups, including us, have reported the cross-coupling
reactions of nonactivated alkyl halides with Grignard reagents
by using iron catalysts.3h-3j,3m-3o,3t,3u In 2004, we introduced
TMEDA as a Lewis basic additive into the iron-catalyzed cross-
coupling reaction to obtain the desired reactivity toward the
alkyl halides.3h Although high selectivity and reactivity were
achieved by using TMEDA with the optimized experimental
procedure, large excess of the additive was required. In order to
control the reaction by using a catalytic amount of additives
instead of TMEDA, we continued the study and have developed
new ortho-phenylene-bisphosphine ligands, which bear periph-
eral steric bulk around the iron center.4 We report herein a new
Kumada-Tamao-Corriu coupling between various nonactivated
alkyl halides and aryl Grignard reagents effected by low catalyst
loading (0.5 to 3 mol %) of the iron-bisphosphine complex.
According to Nagashima’s report on the reaction of
dimesityliron(II)-N,N,N¤,N¤-tetramethylethylenediamine, [Mes2-
FeII(tmeda)], with an alkyl halide (eq 1), it was suggested that
the reactive iron species should adopt a tetrahedral geometry in
high-spin state (S = 2).5
PhMgBr
2
(1.5 equiv)
iron catalyst
(0.5 mol%)
4
5
Ph
THF, 0 °C
25 °C, 20 min,
slow addition
3
Yield/%a Recovery/%a
Entry Iron catalyst
3
4
5
2
1
FeCl3
21 69
50 20
6
4
0
0
0
25
1
2b [FeCl2(dppbz)2]
3b [FeCl2(3,5-t-Bu2-SciOPP)] 84 14
[FeCl2(3,5-t-Bu2-SciOPP)] 92
aThe yield and recovery were determined by GC analysis using
undecane as an internal standard. All data are the average of
two or three experiments. c0.5 mol % of 3,5-t-Bu2-SciOPP was
used as an additive.
4c
8
0
b
benzene6 (hereafter named 3,5-t-Bu2-SciOPP4c,7) and also
prepared its iron(II) chloride complex [FeCl2(3,5-t-Bu2-
SciOPP)].4 The iron complex exhibited the above-mentioned
properties of the catalytically active iron species, and we
anticipated that the bulky substituents would bring about
peripheral steric bulkiness around the iron center to maintain
the desired properties upon transmetalation with aryl Grignard
reagents, emulating Nagashima’s [Mes2FeII(tmeda)].
Having the iron complex in hand, we examined the coupling
reaction of alkyl halides with aryl Grignard reagents in the
presence of catalytic amounts of [FeCl2(3,5-t-Bu2-SciOPP)].
Table 1 summarizes the results of catalyst screening for the
reaction of bromocycloheptane (2) with the phenyl Grignard
reagent. To a THF solution of 2 and the iron complex was added
dropwise the Grignard reagent over 20 min at 25 °C according to
a procedure we reported previously.3h In the absence of the
phosphine ligand, coupling product (3) was obtained in 21%
Me
Me
Me
Me
Me
Me
Me
Me
N
N
N
N
+
+
n-C8H16 Mes
n-C8H16 Br
FeII
FeII
ð1Þ
THF
30 °C, 9.5 h
Mes
Mes Mes
Br
[MesFeBr(tmeda)]
90% yield
[Mes2Fe(tmeda)]
76% yield
As shown in Scheme 1, we designed and synthesized a novel
ortho-phenylene-tethered bisdphosphine ligand possessing bulky
substituents at the 3,5-positions of phenyl groups on the phos-
phorus atoms, 1,2-bis{bis[3,5-di(t-butyl)phenyl]phosphino}-
Chem. Lett. 2011, 40, 1030-1032
© 2011 The Chemical Society of Japan