Iridium-catalyzed enantioselective C-H alkylation of ferrocenes with alkenes using chiral diene ligands

Article abstract of DOI:10.1002/anie.201402518

The first catalytic and enantioselective C-H alkylation of ferrocene derivatives with various alkenes was achieved. A cationic iridium complex, having a chiral diene ligand, and an isoquinolyl moiety as a directing group are essential for regioselective and enantioselective C-H bond activation. Director's cut: The first catalytic and enantioselective C-H alkylation of ferrocene derivatives with various alkenes was achieved. A cationic iridium complex, having a chiral diene ligand, and an isoquinolyl moiety as a directing group are essential for regioselective and enantioselective C-H bond activation. coe=cyclooctene, NaBARF=sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate.

Full text of DOI:10.1002/anie.201402518

Angewandte
Chemie
DOI: 10.1002/anie.201402518
À
C H Activation
À
Iridium-Catalyzed Enantioselective C H Alkylation of Ferrocenes
with Alkenes Using Chiral Diene Ligands**
Takanori Shibata* and Tsubasa Shizuno
À
Abstract: The first catalytic and enantioselective C H alkyla-
tion of ferrocene derivatives with various alkenes was achieved.
A cationic iridium complex, having a chiral diene ligand, and
an isoquinolyl moiety as a directing group are essential for
co-workers reported a palladium-catalyzed enantioselective
arylation, alkenylation, and annulation of aminomethylferro-
cene.[10] Described herein is the iridium-catalyzed enantiose-
letive alkylation of (isoqunolin-1-yl)ferrocene (1a) using
chiral diene ligands, and it serves as the first example of an
À
regioselective and enantioselective C H bond activation.
À
asymmetric reaction initiated by enantioselective C H bond
T
ransition metal catalyzed C C bond formation initiated by
cleavage using chiral diene ligands.[11]
À
À
C H bond cleavage is an ideal synthetic protocol because pre-
activation of the substrate is unnecessary, and thus makes
possible a shorter and more atom-economical synthesis.[1]
Since monumental work of Murai et al. on the ruthenium-
Ferrocene is a historically important organometallic
compound, and the application of its derivatives in medicinal
chemistry and material science has attracted much atten-
tion.[12] With regard to organic synthesis, the planar chirality
of ferrocene having two different substituents is utilized.[13] In
fact, a chiral diphosphine, xyliphos, which has a planar-chiral
ferrocene scaffold, is used in iridium-catalyzed hydrogenation
on a scale of 10000 ton per year.[14] However, the preparation
of planar-chiral ferrocenes has relied on optical resolution or
diastereoselective approaches.[15] With respect to enantiose-
lective synthesis, ortho lithiation using chiral diamines has
been the most successful example.[16] Recently, Ogasawara
reported a molybdenum-catalyzed asymmetric olefin meta-
thesis for the creation of planar chirality in ferrocene.[17] In
contrast, we recently reported the [Ir(cod)2]BARF-catalyzed
catalyzed C H alkylation,[2] various transition-metal catalysts
À
À
have been reported for C H bond activation using directing
groups such as carbonyl and imino groups.[3] Some reactions
have been used as key steps in natural product synthesis.[4]
À
However, catalytic and asymmetric C C bond formation
initiated by enantioselective C(sp ) H bond cleavage is still
a challenging topic. Secondary C H bond cleavage induces
a chiral center, but the C(sp ) H bond is intrinsically more
3
À
À
3
À
2
À
difficult to cleave than the C(sp ) H bond. The first successful
example was a chiral copper-catalyzed alkynylation at the
benzylic position.[5] Yu and co-workers reported an enantio-
selective palladium-catalyzed arylation of cyclopropane
rings.[6] Chiral rhodium-catalyzed intramolecular alkylation
À
C H alkenylation and alkylation of ferrocenes possessing
a directing group.[18] A mechanistic study revealed that
cycloocta-1,5-diene (cod) coordinated to the metal center
throughout the entire catalytic cycle, and phosphine ligands
deactivated the catalytic activity. The results were quite
at the allylic position is another successful example.[7] We also
3
À
reported enantioselective C(sp ) H alkylation using a chiral
iridium catalyst.[8] Another approach to the creation of
2
À
À
a chiral center is desymmetrization initiated by C(sp ) H
bond cleavage. Yu and co-workers reported the asymmetric
synthesis of chiral diarylmethane compounds initiated by
enantioselective C(sp ) H bond cleavage. The generation
of planar chirality by enantioselective C(sp ) H bond cleav-
different from those in other iridium-catalyzed C H bond
activations, where phosphine ligands were considered to be
critical for efficient transformation.[19] Against this back-
2
[9]
À
À
ground, we investigated the enantioselective C H bond
2
À
activation of ferrocene by using an iridium/chiral diene
catalyst.
age is also fascinating. In the first elegant work on the
À
enantioselective C H bond activation of ferrocene, You and
We chose (isoquinolin-1-yl)ferrocene (1a) as a model
substrate and examined the reaction with ethyl acrylate (2a)
(Table 1). As representative diene ligands, Hayashiꢀs diene
L1[20] and Carreiraꢀs diene L2[21,22] were used in combination
with [{Ir(coe)2Cl}2] and sodium tetrakis[3,5-bis(trifluorome-
thyl)phenyl]borate (NaBARF) in toluene (entries 1 and 2).[23]
The monoalkylated product 3aa was obtained in good yield in
both cases, but the enantioselectivities differed. In this
transformation, the rhodium counterpart was completely
ineffective (entry 3). We additionally examined various
analogues of L2 derived from carvone (entries 4–7).[24] A p-
tolyl group gave the best results, and the ee value exceeded
90% (entry 5).
[*] Prof. Dr. T. Shibata, T. Shizuno
Department of Chemistry and Biochemistry
School of Advanced Science and Engineering
Waseda University, Shinjuku, Tokyo 169-8555 (Japan)
E-mail: tshibata@waseda.jp
Homepage: http://www.chem.waseda.ac.jp/shibata/
Prof. Dr. T. Shibata
ACT-C, Japan Science and Technology Agency (JST)
4-1-8 Honcho Kawaguchi, Saitama, 332-0012 (Japan)
[**] This work was supported by a Grand-in-aid for Scientific Research
on Innovative Area, “Molecular Activation Directed toward
Straightforward Synthesis”, MEXT, JST, ACT-C, and grants for
Excellent Graduate School (Practical Chemical Wisdom), Waseda
University, MEXT (Japan).
We next examined the effect of the directing group (DG)
on ferrocene on the enantioselectivity and regioselectivity
using exactly one equivalent of ethyl acrylate (Table 2). Even
a simple pyridyl group induced excellent enantioselectivity,
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201402518.
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À
Table 1: Screening of chiral dienes in the iridium-catalyzed C H
alkylation of 1a.
2-yl group, only trace amounts of the dialkylated products
were detected (entries 4 and 5). These results imply that the
substituent adjacent to the ferrocenyl group controls the
regioselectivity, and the coordination of the nitrogen atom to
the metal center leads to excellent enantioselectivity. The
À
pyrimidyl group was ineffective in this C H alkylation and
the monoalkylated products 3 were not obtained (entries 6
and 7).[26]
Table 3: Substrate of scope with respect to the alkenes.[a]
Entry
Alkene
t [h]
3
Yield [%][b]
ee [%][c]
Entry
Chiral diene
Yield [%][a]
ee [%][b]
1
2
L1
L2
L2
L3
L4
L5
L6
80
91
n.r.
72
90
60
85
<2
84
–
22
91
85
59
3[c]
4
1[c]
2b
48
24
38 (3ab)
75
5[d]
6
7
[a] Yield of the isolated product. [b] The ee value was determined by
HPLC analysis using a chiral stationary phase. [c] In place of [{Ir-
(coe)2Cl}2], [{Rh(coe)2Cl}2] was used. [d] The reaction time was 7 h.
n.r.=no reaction. coe=cyclooctene.
2
2c
83 (3ac)
88
Table 2: Effect of directing group on the enantioselectivity and regiose-
lectivity.
3
4
2d
24
24
73 (3ad)
93
79
2e
96 (3ae)
Entry
Directing group
3
4
Yield [%][a]
ee [%][b]
Yield [%][a]
1
2
3
4
5
6
7
pyridin-2-yl
1b
1c
1d
1e
1a
1 f
33 (3ba)
32 (3ca)
45 (3da)
77 (3ea)
88 (3aa)
trace
97
98
96
93
90
–
ca. 30[c]
ca. 30[c]
ca. 25[c]
trace
5[d]
2 f
24
64 (d.r.=2:1)
(3af)[e]
83
5-Me-pyridin-2-yl
4-Me-pyridin-2-yl
3-Me-pyridin-2-yl
isoquinolin-1-yl
pyrimidin-2-yl
pyrimidin-4-yl
trace
ca. 35[c]
–
1g
n.r.
–
[a] Yield of the isolated product. [b] The ee value was determined by
HPLC analysis using a chiral stationary phase. [c] Inseparable impurities
were included.
6
2g
24
78 (3ag)
77
[a] The reaction conditions were the same as those used for the reactions
in Table 2 except the reaction time. [b] Yield of the isolated product.
[c] The ee value was determined by HPLC analysis using a chiral
stationary phase. [d] Four equivalent amounts of alkenes were used.
[e] The stereostructures of the diastereomers could not be determined.
The ee value of the minor diastereomer was 85%.
but the yield of the monoalkylated adduct 3ba was low and
a significant amount of the achiral dialkylated product 4ba
was also obtained (entry 1).[25] A methyl group at the 5- or 4-
position could not suppress the second alkylation, but in the
case of a 3-methylpyridin-2-yl group, as well as an isoquinolin-
2
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Several alkenes were subjected to the reaction with
(isoquinolin-1-yl)ferrocene (1a; Table 3). Methyl vinyl
ketone (2b) was too reactive, and the chiral ketone 3ab was
obtained, albeit in low yield (entry 1). The reactions of
allylbenzene and allylsilane gave the corresponding mono-
alkylated products 3ac and 3ad (entries 2 and 3). Notably,
a simple alkene, oct-1-ene (2e), could be used as a coupling
partner (entry 4). The reaction of methyl methacrylate (2 f)
also proceeded, but the products were obtained as a 2:1
diastereomeric mixture (entry 5). Norbornene (2g) was also
a good alkylating reagent (entry 6).[27]
isoquinolin-1-yl moiety was observed [Eq. (1)]. When the
reaction was conducted in the presence of both D2O and 2-
vinylnaphthalene (2p), and was quenched within 3 hours,
deuteration at both the a and b-position of the naphthalene
Table 4 shows the results of the reaction of 1a with styrene
derivatives under the same reaction conditions.[24] In each
case, high to excellent yields were achieved, but the branched
ring of the product 3ap(L) was observed [Eq. (2)]. Two
vinylic positions of the recovered 2p ring were also deuter-
Table 4: Substrate scope of with respect to the styrenes.
À
ated. These results imply that the C H bond on ferrocene is
cleaved under the present reaction conditions and the alkene
insertion pathway is reversible.[8b]
Entry Ar
t [h] Yield [%][b] L/B[b]
ee [%][c]
1
2
3
4
5
6
7
8
9
C6H5
2h
2i
2j
2k
2l
2m
2n
2o
7
7
96 (3ah)
92 (3ai)
96 (3aj)
95 (3ak)
99 (3al)
99 (3am)
86 (3an)
69 (3ao)
95 (3ap)
3:1
>20:1 83
2:1
2:1
2:1
89 (91)[d]
2-BrC6H4
3-BrC6H4
4-BrC6H4
4-ClC6H4
2-CF3C6H4
3-CF3C6H4
C6F5
24
24
12
7
24
24
7
87
83
87
>20:1 82
2:1
87 (91)[e]
>20:1 51 (95)[f]
naphthalen-2-yl 2p
1:1
91
[a] Yield of the isolated product. [b] The ratio of linear and branched
adducts was determined by NMR analysis. [c] The ee value was
determined by HPLC analysis using a chiral stationary phase. The
ee value of the linear products 3ah–ap(L) was listed, unless otherwise
noted. [d] The ee value using L2 as a chiral ligand is described in the
parentheses. [e] The ee value of the branched adduct 3an(B) is described
within the parentheses. It was obtained as a single diastereomer, but its
stereostructure could not be determined. [f] The ee value after recrys-
tallization of the obtained 3ao(L) is described within the parentheses.
In conclusion, we have developed a catalytic and enan-
À
tioselective C H alkylation of (isoquinolin-1-yl)ferrocene
with various alkenes. The combination of a cationic iridium
complex with a chiral diene ligand is essential for regiose-
À
lective and enantioselective C H bond activation. This
2
À
reaction is the first example of the enantioselective C(sp )
H alkylation of ferrocenes. Further studies on the scope of the
alkenes and application of the obtained planar-chiral ferro-
cenes are underway in our laboratory.
alkylated products 3(B) were also obtained as minor products.
In the reaction with ortho-substituted styrenes, the linear
adducts 3ai(L) and 3am(L) were the only detectable products
(entries 2 and 6). The reaction of pentafluorostyrene (2o)
gave only the linear product 3ao(L) (entry 8). The ee value
was moderate, but recrystallization of the solid sample
drastically improved the enantiomeric purity to 95%, and
the structure of the product was determined to be R form by
X-ray analysis.[28] The ee value of the linear products was
generally good to high and a comparable ee value of the
branched product 3an(B) was ascertained (entry 7).[29]
Received: February 17, 2014
Published online: && &&, &&&&
À
Keywords: alkylation · C H activation · enantioselectivity ·
.
iridium · synthetic methods
[1] For selected reviews, see: a) V. Ritleng, C. Sirlin, M. Pfeffer,
Chem. Rev. 2002, 102, 1731 – 1770; b) F. Kakiuchi, N. Chatani,
Adv. Synth. Catal. 2003, 345, 1077 – 1101; c) K. Godula, D.
Sames, Science 2006, 312, 67 – 72; d) H. M. L. Davies, J. R.
Manning, Nature 2008, 451, 417 – 424; e) X. Chen, K. M. Engle,
D. H. Wang, J.-Q. Yu, Angew. Chem. 2009, 121, 5196 – 5217;
Angew. Chem. Int. Ed. 2009, 48, 5094 – 5115; f) T. W. Lyons, M. S.
As a preliminary mechanistic study, we performed label-
ling experiments. When 1a was subjected to the reaction
conditions in the presence of D2O and the absence of alkene,
À
deuteration of C H bond on ferrocene adjacent to the
Angew. Chem. Int. Ed. 2014, 53, 1 – 5
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www.angewandte.org
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These are not the final page numbers!

.
Angewandte
Communications
Sanford, Chem. Rev. 2010, 110, 1147 – 1169; g) C.-L. Sun, B.-J. Li,
Z.-J. Shi, Chem. Commun. 2010, 46, 677 – 685; h) C. S. Yeung,
V. M. Dong, Chem. Rev. 2011, 111, 1215 – 1292; i) S. H. Cho, J. Y.
Kim, J. Kwak, S. Chang, Chem. Soc. Rev. 2011, 40, 5068 – 5083.
[2] S. Murai, F. Kakiuchi, S. Sekine, Y. Tanaka, A. Kamatani, M.
Sonoda, N. Chatani, Nature 1993, 366, 529 – 531.
[3] For recent reviews, see: a) Handbook of C-H Transformations
(Ed.: G. Dyker), Wiley-VCH, Weinheim, 2005; b) D. Alberico,
M. E. Scott, M. Lautens, Chem. Rev. 2007, 107, 174 – 238; c) T.
Kitamura, Eur. J. Org. Chem. 2009, 1111 – 1125; d) R. Giri, B.-F.
Shi, K. M. Engle, N. Maugel, J.-Q. Yu, Chem. Soc. Rev. 2009, 38,
118, 685 – 686; c) Y. Nishibayashi, Y. Arikawa, K. Ohe, S.
Uemura, J. Org. Chem. 1996, 61, 1172 – 1174.
[17] a) M. Ogasawara, S. Watanabe, L. Fan, K. Nakajima, T.
Takahashi, Organometallics 2006, 25, 5201 – 5203; b) M. Ogasa-
wara, S. Watanabe, K. Nakajima, T. Takahashi, J. Am. Chem.
Soc. 2010, 132, 2136 – 2137; c) M. Ogasawara, S. Arae, S.
Watanabe, K. Nakajima, T. Takahashi, Chem. Eur. J. 2013, 19,
4151 – 4154.
[18] S. Takebayashi, T. Shibata, Organometallics 2012, 31, 4114 –
4117.
[19] a) K. Tsuchikama, M. Kasagawa, Y. Hashimoto, K. Endo, T.
Shibata, J. Organomet. Chem. 2008, 693, 3939 – 3942; b) K.
Tsuchikama, Y. Hashimota, K. Endo, T. Shibata, Adv. Synth.
Catal. 2009, 351, 2850 – 2854; c) K. Tsuchikama, M. Kasagawa,
K. Endo, T. Shibata, Org. Lett. 2009, 11, 1821 – 1823; d) K.
Tsuchikama, M. Kasagawa, K. Endo, T. Shibata, Synlett 2010,
97 – 100; e) T. Shibata, Y. Hashimoto, M. Otsuka, K. Tsuchi-
kama, K. Endo, Synlett 2011, 2075 – 2079; f) T. Shibata, H.
Hirashima, M. Kasagawa, K. Tsuchikama, K. Endo, Synlett 2011,
2171 – 2176; g) S. Pan, N. Ryu, T. Shibata, J. Am. Chem. Soc.
2012, 134, 17474 – 17477; h) S. Pan, N. Ryu, T. Shibata, Adv. Syn.
Catal. 2014, 356, 929 – 933.
[20] a) N. Tokunaga, Y. Otomaru, K. Okamoto, K. Ueyama, R.
Shintani, T. Hayashi, J. Am. Chem. Soc. 2004, 126, 13584 – 13585;
b) R. Shintani, T. Hayashi, Aldrichimica Acta 2009, 42, 31 – 38.
[21] a) C. Fischer, C. Defieber, T. Suzuki, E. M. Carreira, J. Am.
Chem. Soc. 2004, 126, 1628 – 1629; b) C. Defieber, H. Grꢃtz-
macher, E. M. Carreira, Angew. Chem. 2008, 120, 4558 – 4579;
Angew. Chem. Int. Ed. 2008, 47, 4482 – 4502.
[22] a) C. Defieber, J.-F. Paquin, S. Serna, E. M. Carreira, Org. Lett.
2004, 6, 3873 – 3876; b) J.-F. Paquin, C. R. J. Stephenson, C.
Defieber, E. M. Carreira, Org. Lett. 2005, 7, 3821 – 3824; c) J.-F.
Paquin, C. Defieber, C. R. J. Stephenson, E. M. Carreira, J. Am.
Chem. Soc. 2005, 127, 10850 – 10851; d) K. Aikawa, S. Akuta-
gawa, K. Mikami, J. Am. Chem. Soc. 2006, 128, 12648 – 12649;
e) T. Gendrineau, O. Chuzel, H. Eijsberg, J.-P. Genet, S. Darses,
Angew. Chem. 2008, 120, 7783 – 7786; Angew. Chem. Int. Ed.
2008, 47, 7669 – 7672; f) K. Aikawa, Y. Takabayashi, S. Kawau-
chi, K. Mikami, Chem. Commun. 2008, 5095 – 5097; g) P. Four-
nier, R. Fiammengo, A. Jaeschke, Angew. Chem. 2009, 121,
4490 – 4493; Angew. Chem. Int. Ed. 2009, 48, 4426 – 4429; h) T.
Gendrineau, J.-P. Genet, S. Darses, Org. Lett. 2009, 11, 3486 –
3489; i) S. J. Mahoney, A. M. Dumas, E. Fillion, Org. Lett. 2009,
11, 5346 – 5349; j) T. Gendrineau, J.-P. Genet, S. Darses, Org.
Lett. 2010, 12, 308 – 310; k) J. Keilitz, S. G. Newman, M. Lautens,
Org. Lett. 2013, 15, 1148 – 1151.
[23] The solvent and counter anion effect were shown in Table S1 in
the Supporting Information.
[24] The ligand screening of the reaction with styrene was shown in
Table S2.
[25] The kinetic resolution of racemic 3ba was examined but the
ee value of recovered 3ba was low (31% ee; see the Supporting
Information).
[26] Other directing groups such as acetyl and dimethylaminomethyl
groups were ineffective and no reaction proceeded under the
same reaction conditions.
[27] The reaction with ynones such as methyl propiolate and methyl
3-phenylpropiolate did not proceed under the same reaction
conditions.
[28] The stereostructure of 3ao(L) is shown in the Supporting
Information.
À
3242 – 3272; e) C H Activation (Eds.: J.-Q. Yu, Z. Shi), Springer,
Berlin, 2010; f) O. Daugulis, Top. Curr. Chem. 2010, 292, 57 – 84;
g) D. A. Colby, R. G. Bergman, J. A. Ellman, Chem. Rev. 2010,
110, 624 – 655.
[4] a) J. Cossy, S. Arseniyadis, Modern Tools for the Synthesis of
Complex Bioactive Molecules, 2012, 1 – 32; b) J. Yamaguchi,
A. D. Yamaguchi, K. Itami, Angew. Chem. 2012, 124, 9092 –
9142; Angew. Chem. Int. Ed. 2012, 51, 8960 – 9009; c) D. Y.-K.
Chen, S. W. Youn, Chem. Eur. J. 2012, 18, 9452 – 9474.
[5] Z. Li, C.-J. Li, Org. Lett. 2004, 6, 4997 – 4999.
[6] M. Wasa, K. M. Engle, D. W. Lin, E. J. Yoo, J.-Q. Yu, J. Am.
Chem. Soc. 2011, 133, 19598 – 19601.
[7] Q. Li, Z.-X. Yu, Angew. Chem. 2011, 123, 2192 – 2195; Angew.
Chem. Int. Ed. 2011, 50, 2144 – 2147.
[8] a) S. Pan, K. Endo, T. Shibata, Org. Lett. 2011, 13, 4692 – 4695;
b) S. Pan, Y. Matsuo, K. Endo, T. Shibata, Tetrahedron 2012, 68,
9009 – 9015.
[9] a) B.-F. Shi, N. Maugel, Y.-H. Zhang, J.-Q. Yu, Angew. Chem.
2008, 120, 4960 – 4964; Angew. Chem. Int. Ed. 2008, 47, 4882 –
4886; b) B.-F. Shi, Y.-H. Zhang, J. K. Lam, D.-H. Wang, J.-Q. Yu,
J. Am. Chem. Soc. 2010, 132, 460 – 461; c) X.-F. Cheng, Y. Li, Y.-
M. Su, F. Yin, J.-Y. Wang, J. Sheng, H. U. Vora, X.-S. Wang, J.-Q.
Yu, J. Am. Chem. Soc. 2013, 135, 1236 – 1239.
[10] a) D.-W. Gao, Y.-C. Shi, Q. Gu, Z.-L. Zhao, S.-L. You, J. Am.
Chem. Soc. 2013, 135, 86 – 89; b) C. Pi, Y. Li, X. Cui, H. Zhang, Y.
Han, Y. Wu, Chem. Sci. 2013, 4, 2675 – 2679; c) Y.-C. Shi, R.-F.
Yang, D.-W. Gao, S.-L. You, Beilstein J. Org. Chem. 2013, 9,
1891 – 1896.
[11] Recently, a iridium/chiral diene complex for the catalysis of
2
À
a [3+2] cycloaddition was reported, and was initiated by C(sp )
H activation along with enantioselective 1,3-diene insertion: T.
Nishimura, M. Nagamoto, Y. Ebe, T. Hayashi, Chem. Sci. 2013, 4,
4499 – 4504.
[12] a) M. F. R. Fouda, M. M. Abd-Elzaher, R. A. Abdelsamaia,
A. A. Labib, Appl. Organomet. Chem. 2007, 21, 613 – 625;
b) T.-L. Choi, K.-H. Lee, W.-J. Joo, S. Lee, T.-W. Lee, M. Y.
Chae, J. Am. Chem. Soc. 2007, 129, 9842 – 9843; c) W. A. Amer,
L. Wang, A. M. Amin, L. Ma, H. Yu, J. Inorg. Organomet.
Polym. 2010, 20, 605 – 615; d) T. Daeneke, T.-H. Kwon, A. B.
Holmes, N. W. Duffy, U. Bach, L. Spiccia, Nat. Chem. 2011, 3,
211 – 215; e) M. Tropiano, N. L. Kilah, M. Morten, H. Rahman,
J. J. Davis, P. D. Beer, S. Faulkner, J. Am. Chem. Soc. 2011, 133,
11847 – 11849.
[13] a) R. Gꢁmez Arrayꢂs, J. Adrio, J. C. Carretero, Angew. Chem.
2006, 118, 7836 – 7878; Angew. Chem. Int. Ed. 2006, 45, 7674 –
7715; b) Chiral Ferrocenes in Asymmetric Catalysis, (Eds.: L.-X.
Dai, X.-L. Hou), Wiley-VCH, Weinheim, 2010.
[14] H.-U. Blaser, Adv. Synth. Catal. 2002, 344, 17 – 31.
[15] A recent review: D. Schaarschmidt, H. Lang, Organometallics
2013, 32, 5668 – 5704.
[16] Pioneering works: a) D. Price, N. S. Simpkins, Tetrahedron Lett.
1995, 36, 6135 – 6136; b) M. Tsukazaki, M. Tinkl, A. Roglans,
B. J. Chapell, N. J. Taylor, V. Snieckus, J. Am. Chem. Soc. 1996,
[29] The reaction of diphenylacetylene proceeded to give mono-
alkenylated product in 66%, but its ee value was below 2%.
4
www.angewandte.org
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Communications
À
C H Activation
T. Shibata,* T. Shizuno
&&&& — &&&&
À
Iridium-Catalyzed Enantioselective C H
Alkylation of Ferrocenes with Alkenes
Using Chiral Diene Ligands
Director’s cut: The first catalytic and
isoquinolyl moiety as a directing group
À
enantioselective C H alkylation of ferro-
are essential for regioselective and enan-
À
cene derivatives with various alkenes was
achieved. A cationic iridium complex,
having a chiral diene ligand, and an
tioselective C H bond activation. coe=
cyclooctene, NaBARF=sodium tetrakis-
[3,5-bis(trifluoromethyl)phenyl]borate.
Angew. Chem. Int. Ed. 2014, 53, 1 – 5
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!