Asymmetric Synthesis of Chiral Cyclopentanes Bearing an All-Carbon Quaternary Stereocenter by Zirconium-Catalyzed Double Carboalumination

Article abstract of DOI:10.1002/anie.201706198

Herein, we report a zirconium-catalyzed enantio- and diastereoselective inter/intramolecular double carboalumination of unactivated 2-substituted 1,5-dienes, which provides efficient and direct access to chiral cyclopentanes through the generation of two

Full text of DOI:10.1002/anie.201706198

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Accepted Article
Title: Asymmetric Synthesis of Chiral Cyclopentanes Bearing an All-
Carbon Quaternary Stereocenter via Zr-catalyzed Doubled
Carboalumination
Authors: Shiqing Xu, Chuan Wang, Masato Komiyama, Yasuhiko
Tomonari, and Ei-ichi Negishi
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201706198
Angew. Chem. 10.1002/ange.201706198
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10.1002/anie.201706198
Angewandte Chemie International Edition
COMMUNICATION
Asymmetric Synthesis of Chiral Cyclopentanes Bearing an
All-Carbon Quaternary Stereocenter via Zr-catalyzed Doubled
Carboalumination
Shiqing Xu,†,[a] Chuan Wang,†,[a,b] Masato Komiyama,[a] Yasuhiko Tomonari,[a] and Ei-ichi
Negishi*[a]
Dedicated to Professor Victor Snieckus on the occasion of his 80th birthday
Abstract: Herein we report
a
Zr-catalyzed enantio- and
centers, are still very rare.[6] Herein, we report an efficient Zr-
catalyzed doubled carboalumination of unactivated 1,5-dienes to
provide a variety of chiral cyclopentanes bearing an all-carbon
quaternary stereogenic center through the formation of two new
C–C bonds as well as a C–Al bond.
diastereoselective inter–intramolecular doubled carboalumination of
unactivated 2-substituted-1,5-dienes which provides an efficient and
direct access to chiral cyclopentanes with generation of two
stereocenters including an all-carbon quaternary stereocenter
generally in excellent diastereomeric ratios and high enantiomeric
excesses. This tandem carboalumination process creates two new C–
C bonds as well as a C–Al bond which can be in-situ oxidized with O2
or hydrolyzed. Furthermore, the obtained chiral cyclopentanes can be
readily functionalized to provide various chiral compounds.
In the last decades, zirconium-catalyzed asymmetric
carboalumination of alkenes (ZACA) developed by our group has
proven to be a powerful tool for asymmetric synthesis of versatile
chiral building blocks as well as various natural products
containing alkyl-branched tertiary stereocenters, in many cases in
enantiomerically pure form with the assistance of either lipase-
catalyzed acetylation through kinetic resolution of the initial ZACA
products or statistical enantiometric amplification.[1,2] It is
important to note that the previous examples are limited to the
construction of chiral tertiary stereocenters. Cyclopentanes
bearing an all-carbon quaternary stereocenter can be found in
numerous natural products and synthetic biologically active
compounds.[3] However, construction of all-carbon quaternary
stereocenters in a highly enantioselective manner, especially
from simple starting materials, is still a formidable challenge for
organic chemists.[4] Transition metal-catalyzed intramolecular C–
C bond formation reactions provide powerful methods for the
synthesis of various carbo- and heterocyclic molecules. Thus,
extensive studies have been performed on transition metal-
catalyzed cyclizations of α,ω-bifunctional compounds such as
diynes, enynes, and dienes.[5] In contrast, studies of cyclization of
dienes through an intermolecular carbometalation followed by a
cascade diastereoselective intramolecular carbometalation,
especially those cases with the formation of all-carbon quaternary
Scheme 1. Optimum reaction conditions for the Zr-catalyzed stereoselective
doubled carboalumination of 2-phenyl-1,5-hexadiene.
For optimization of the reaction conditions, we used 2-phenyl
1,5-hexadiene (1a) as the standard substrate. After a brief
screening of solvents and additives and the tuning of temperature
and catalyst loading, the optimal results concerning both
enantioselectivity and the efficiency were achieved when the
reaction was conducted in chloroform using 3 mol% (−)-
[7]
Zr(NMI)2Cl2 (NMI: 1-neomenthylindenyl) as catalyst and 1
equivalent amount of water as additive (Scheme 1).[8] Presumably,
the addition of water to AlMe3 leads to the generation of MAO or
a more active species as a Lewis acid activator or co-activator to
assist the formation of the active cationic zirconium complex.[9]
Remarkably, the initial intermolecular ZACA reaction proceeded
exclusively at the monosubstitued olefin followed by
intramolecular carboalumination[10] and in-situ oxidation with
oxygen providing the cyclopentane 2a as the sole cyclic product.
After establishing the optimum reaction conditions, we started
to evaluate the substrate scope of this doubled carboalumination
reaction (Table 1). We first reacted diverse 1,5-dienes with AlMe3
followed by in-situ oxidation with O2. Generally, various 1,5-
dienes with different substituents of the disubstituted double bond,
such as aryls with electron-withdrawing and electron-donating
groups, naphthyl, furyl, and c-hexyl underwent tandem
carboalumination smoothly affording products 2a-i in moderate to
good yields, excellent diastereomeric ratios and good
enantiomeric excesses. Subsequently, we investigated the
substrate scope further by employing different trialkylaluminum
[a]
[b]
Dr. S. Xu, Dr. C. Wang, Mr. M. Komiyama, Dr. Y. Tomonari, Prof.
Dr. E. Negishi
Herbert C. Brown Laboratories of Chemistry, Purdue University
560 Oval Drive, West Lafayette, IN-47906 (USA)
E-mail: negishi@purdue.edu
Dr. C. Wang
Department of Chemistry, University of Science and Technology of
China. 96 Jinzhai Road, Heifei, Anhui, 230026 (P. R. China)
† These authors contributed equally to this work
Supporting information for this article is given via a link at the end of
the document.
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10.1002/anie.201706198
Angewandte Chemie International Edition
COMMUNICATION
Table 1. Evaluation of the substrate scope of the doubled carboalumination[a]
Table 2. Investigation of the effect of heteromatom of alkyl substituents on
diastereoselectivity[a]
Yield
[%][b]
71
66
60
53
47
46
54
60
72
55
41
46
55
54
41
ee
Entry
2
R1
R2
dr[c]
[%][d]
87 (‒87[e]
85
Yield
[%][b]
66
85
51
72
40
75
72
82
72
80
58
ee
Entry
2
R1
R2
dr[c]
[%][c]
‒83[f]
‒83[f,h]
n.d.[i]
82
1
2
3
4
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
Et
Et
Et
n-Pr
n-Pr
Me
Me
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
67:33[i]
>98:2
>98:2
>98:2
71:29
>98:2
>98:2
98:2[i]
97:3[i,l]
)
4-FC6H4
4-ClC6H4
3-ClC6H4
4-MeOC6H4
2-Naphthyl
2-Furyl
c-Hex
Me
Ph
4-ClC6H4
3-ClC6H4
Bn
1
p
q
r
i
s
t
CH2OH
CH2OTBDPS
CH2NBn2
Me
Me
Me
Me
Me
Me
Me
Me
Et
98:2
‒88[e]
87
83
2[g]
3
97:3[h]
>98:2[d]
67:33
72:28[d]
98:2
5[f,g]
6[g]
7
4
5
6
Me
84
CH2CH2TBDPS
CH2CH2OH
CH2CH2OH
CH2CH2OTBDPS
CH2CH2OH
CH2CH2OTBDPS
CH2CH2OTBDPS
86[e]
‒83[f]
‒83[f]
‒83[f,h]
‒95[f]
‒95[f,h]
n.d.[i]
82
79[h]
82[i]
90
7[j]
8[g]
9[j]
10[j]
11[j]
t
98:2
8
9[g]
10[j]
11[j]
12[j]
13[j]
14[j]
15[j]
16[g]
17[g,k]
u
v
w
x
87:13[h]
87:13
54:46[h]
53:47
97
97
94
91
Et
Et
Ph
[a] Unless otherwise specified, reactions were performed on a 0.5 mmol scale
of diene 1 using 4.0 equiv trialkylaluminum, 3 mol% (+)-(NMI)2ZrCl2 and 1.0
equiv. H2O in 2.5 mL dichloromethane. [b] Yields of the isolated product after
flash chromatography. [c] Determined by GC-analysis on chiral stationary
phase. [d] Determined by 1H-NMR-spectroscopy. [e] Determined by HPLC-
analysis on chiral stationary phase. [f] (+)-(NMI)2ZrCl2 catalyst was used. [g] 0.2
Equiv H2O was used as additive. [h] Based on the corresponding desilylated
derivative. [i] Not determined. [j] Reactions were performed with 5 mol% catalyst
loading and 1.0 equiv IBAO as additive.
3-ClC6H4
CH2OH
CH2OTBDPS
94
68
85
‒83[e,i]
‒83[e,i,l]
[a] Unless otherwise specified, reactions were performed on a 0.5 mmol scale
of diene 1 using 4.0 equiv trialkylaluminum, 3 mol% (−)-(NMI)2ZrCl2 and 1.0
equiv. H2O in 2.5 mL chloroform. [b] Yields of the isolated product after flash
chromatography. [c] Determined by 1H-NMR-spectroscopy. [d] Determined by
HPLC-analysis on chiral stationary phase. [e] (+)-(NMI)2ZrCl2 catalyst was used.
[f] 6 mol% catalyst was used. [g] Reactions were performed in dichloromethane.
[h] Based on the corresponding benzoate derivative. [i] Determined by GC-
analysis on chiral stationary phase. [j] Reactions were performed in
dichloromethane with 5 mol% catalyst loading and 1.0 equiv IBAO as additive.
[k] 0.2 Equiv H2O was used as additive. [l] Based on the corresponding
desilylated derivative.
As mentioned above, 2-aryl-1,5-dienes with a strictly planar
configuration
generally
showed
the
excellent
diastereoselectivities (dr > 98:2) of the cyclocarbometalation
reactions with AlMe3, AlEt3 and Al(nPr)3 (2a-g,j-I,n,o). However, it
seems that the diastereoselectivity of the carboalumination of 2-
alkyl-substituted dienes, due to more flexible configuration of alkyl
substituents, is influenced by the coordinating heteroatom of the
alkyl substituent at the disubstituted double bond. In order to
investigate this effect, we carried out several control experiments
(Table 2). First, we performed the doubled carboalumination
reactions using the dienes containing an O- or a N-atom at the
allylic position as substrates. In all these cases, excellent
diastereomeric ratios were achieved (entries 1-3, Table 2). In
contrast, when the diene substrates in the absence of a
coordinating heteroatom, the reactions afforded the products with
significantly lower diastereomeric ratios of 67:33 and 72:28,
respectively (entries 4 and 5, Table 2). In addition, when the diene
contains a OH substituent at homoallyl position (entries 6 and 7,
Table 2), the cascade carboalumination reaction by using AlMe3
provided 2t of an excellent diastereoselectivity (dr = 98:2).
However, when CH2CH2OH substituent was replaced with
CH2CH2OTBDPS (entry 8, Table 2), the diastereoselectivity
decreased to 87:13 probably due to the increased steric
hindrance and thus weaker coordination of zirconium complexes
with substrate. This hypothesis was further confirmed by the
findings that the doubled carboalumination products 2v,w,x from
AlEt3 were yielded in significantly lower diastereoselectivities (dr
= 87:13, 54:46, and 53:47, entries 9-11, Table 2) in comparison
to the reactions using AlMe3 (2t,u, dr = 98:2 and 87:13). These
reagents like AlEt3 and Al(nPr)3. In these cases, freshly prepared
IBAO (isobutylaluminoxane) solution[11] instead of water was
preferred in ethyl and higher alkylalumination reactions.
Remarkably, the tandem carboalumination products 2j-o were
formed in relatively higher enantioselectivities (90~97% ee)
compared to the reactions using AlMe3 (79~88% ee). Furthermore,
in the cases of functionalized dienes (entries 16 and 17, Table 1),
the reactions were quenched by adding water furnishing the
products 2p and 2q in high yields and stereoselectivities.
Concerning the diastereoselectivities of this doubled
carboalumination reaction, both the bulkiness and the presence
of a coordinating heteroatom of the substituent at disubstituted
double bond seem to have significant influence. Various dienes
bearing aryl, furyl, c-hexyl substituents (2a-h,j-I,n,o) showed
excellent diastereoselectivites (dr > 98:2), while substrates with
Me (2i) and Bn (2m) substituent exhibited lower
diastereoselectivites. In addition, when the alkyl substituent of the
disubstituted double bond includes a heteroatom (2p,q), the
doubled carboalumination led to the products with high
diastereomeric ratios of 98:2 (2p) and 97:3 (2q), respectively.
Moreover, in the case of 2-phenyl-1,6-diene as substrate, only the
intermolecular ZACA reaction occurred at the monosubstitued
double bond giving an acyclic product.
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10.1002/anie.201706198
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COMMUNICATION
results indicate that not only the presence but also the position of
the heteroatom and steric hindrance are crucial for the
diastereoselectivity of the doubled carboalumination of dienes
bearing alkyl substituents.
A plausible reaction pathway of this doubled carboalumination
reaction is depicted in Scheme 2. Initially, the intermolecular
carbozirconation of 1,5-diene with trialkylaluminum reagent
selectively
proceeds
at
the
sterically
less-hindered
monosubstituted double bond affording a chiral alkyl-zirconium
species I,[12] which subsequently undergoes a diastereoselective
intramolecular carbozirconation on the disubstituted olefin to
generate an all-carbon quaternary stereocenter. Two transition
states II and III are postulated, wherein the latter one is disfavored
due to the repulsion between ZrL2 and R1 in the presence of two
bulky 1-neomenthylindenyl (NMI) ligands. The favored chair-like
seven-membered ring transition state II leads to the formation of
a cyclic organozirconium compound IV. Next, the aluminum–
zirconium
transmetalation
occurs
providing
a
cyclic
organoaluminum compound V, which can be subjected to either
Scheme 3. Derivatization of the doubled carboalumination products.
oxidation or hydrolysis.
The absolute configuration of the compound
7 was
unambiguously determined to be 1S, 3S through X-ray crystal
structure analysis (Figure 1).[16] Therefore, the stereochemistry of
the doubled carboalumination-oxidation products, which were
obtained in the process catalyzed by (+)-Zr(NMI)2Cl2, was
assigned to be 1S, 3S.
Figure 1. X Ray crystal structure of 7.
Scheme 2. Plausible reaction pathway for Zr-catalyzed doubled
carbometalation reaction.
In summary, a doubled carboalumination reaction efficiently
catalyzed by chiral (NMI)2ZrCl2 complex starting from simple
unactivated 1,5-dienes (1) was developed via an inter–
intramolecular cascade carbometalation process. A number of
desired chiral cyclopentanes products with diverse substituents
were obtained in good yields and high diastereo- and
enantioselectivities. This tandem process creates two
stereocenters including an all-carbon quaternary stereocenter
through the formation of two new C–C bonds as well as a C–Al
bond which can be applied to further synthetic transformations.
Moreover, the doubled carboalumination products can be easily
further functionalized to provide various chiral compounds
including an anti-fungicidal agent.
To demonstrate the synthetic utility of this method, doubled
carboalumination products were examined for further
functionalizations (Scheme 3). First, doubled carboalumination
product ent-2a was efficiently converted to 3 by Ir-catalyzed α-
alkylation of ketone with aliphatic alcohol as an electrophile via a
borrowing-hydrogen process for C–C formation.[13] Furthermore,
compound 5 was synthesized in 72% yield by a C–O formation
reaction from 2e. In addition, a biologically active compound 7,
which is reported to bear anti-fungicidal activities,[3b] was readily
synthesized in two steps in a high overall yield (87%) starting from
2c. Moreover, a protected cyclic β-amino acid 9 was also
prepared through Mitsunobu reaction[14] followed by subsequent
oxidative cleavage of phenyl group with RuCl3/NaIO4[15] from 2a
(Scheme 3).
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10.1002/anie.201706198
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COMMUNICATION
[8]
[9]
For details on the optimization of the reaction conditions, see the
Supporting Information, Page S-3.
Acknowledgements
a) E. Y. Chen, T. J. Marks, Chem. Rev. 2000, 100, 1391-1434; b) P. Wipf,
S. Ribe, Org. Lett. 2000, 2, 1713-1716.
We thank the Negishi-Brown Institute, Purdue University and
Teijin Limited for the support of this research. We would also like
to thank Dr. Matthias Zeller for X-ray crystal structure analysis.
[10] For the original examples on intramolecular carboalumination, see: a) G.
Hata, A. Miyake, J. Org. Chem. 1963, 28, 3237-3228; b) R. Rienlcker, G.
F. Gdthel, Angew. Chem. Int. Ed. Engl. 1967, 6, 872; c) L. Clawson, J.
Soto, S. L. Buchwald, M. L. Steigerwald, R. H. Grubbs, J. Am. Chem.
Soc. 1985, 107, 3377-3378; d) P. Rigollier, J. R. Young, L. A, Fowley, J.
R. Stille, J. Am. Chem. Soc. 1990, 112, 9441-9442.
Keywords: ZACA Reaction • All-carbon Quaternary Stereocenter
• Cyclopentanes • Carbometalation • Asymmetric Synthesis
[11] S. Huo, J. Shi, E. Negishi, Angew. Chem. Int. Ed. 2002, 41, 2141-2143;
Angew. Chem. 2002, 114, 2245-2247.
[1]
For reviews on ZACA reaction, see: a) E. Negishi, Angew. Chem. Int. Ed.
2011, 50, 6738-6764; Angew. Chem. 2011, 123, 6870-6897; b) S. Xu, E.
Negishi, Heterocycles 2014, 88, 845-877; c) S. Xu, E. Negishi, Acc.
Chem. Res. 2016, 49, 2158-2168.
[12] a) E. Negishi, Dalton Trans. 2005, 827-848; b) J. M. Camara, R. A. Petros,
J. R. Norton, J. Am. Chem. Soc. 2011, 133, 5263-5273.
[13] K. Taguchi, H. Nakagawa, T. Hirabayashi, S. Sakaguchi, Y. Ishii, J. Am.
Chem. Soc. 2004, 126, 72-73.
[2]
For selected examples on ZACA reaction, see: a) D. Kondakov, E.
Negishi, J. Am. Chem. Soc. 1995, 117, 10771-10772; b) E. Negishi, Z.
Tan, B. Liang, T. Novak, Proc. Natl. Acad. Sci. USA 2004, 101, 5782-
5787; c) B. Liang, T. Novak, Z. Tan, E. Negishi, J. Am. Chem. Soc. 2006,
128, 2770-2771; d) S. Xu, A. Oda, T. Bobinski, H. Li, Y. Matsueda, E.
Negishi, Angew. Chem. Int. Ed. 2015, 54, 9319-9322; Angew. Chem.
2015, 127, 9451-9454.
[14] O. Mitsunobu, M. Yamada, Bull. Chem. Soc. Jpn. 1967, 40, 2380-2382.
[15] J. H. Carlsen, T. Katsuki, S. V. Martin, B. K. Sharpless, J. Org. Chem.
1981, 46, 3936-3938.
[16] CCDC 1523287 (7) contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.
uk/data_request/cif .
[3]
a) M. Suzuki, E. Kurosawa, Bull. Chem. Soc. Jpn. 1979, 52, 3352-3354;
b) J. Clough, D. Griffin, US4684396 A, 1987; c) J. Bryans, T. Capiris, D.
Horwell, C. Kneen, D. Wustrow, WO1999031075 A1, 1999; d) J. Bryans,
L. Meltzer, WO 2002000209 A2, 2002; e) D. Blakemore, J. Bryans, P
Carnell, N. Chessum, M. Field, N. Kinsella, J. Kinsora, S. Osborne, S.
Williams, Bioorg. Med. Chem. Lett. 2010, 20, 362-365; f) G. Doshi, G.
Aggarwal, E. Martis, P. Shanbhag, Int. J. Pharm. Sci. Nanotech. 2011, 4,
1446-1461; g) D. Zaleta-Pinet, I. Holland, M. Munoz-Ochoa, J. Murillo-
Alvarez, J. Sakoff, I. van Altena, A. McCluskey, Org. Med. Chem. Lett.
2014, 4, 1-7; h) M. Harizani, E. Ioannou, V. Roussis in Progress in the
Chemistry of Organic Natural Products, Vol. 102 (Eds.: A. D. Kinghorn,
H. Falk, S. Gibbons, J. Kobayashi), Springer, 2016, pp. 91-252; i) T. Ishii,
T. Nagamine, B. Nguyen, S. Tawata, Rec. Nat. Prod. 2017, 11, 63-68.
For recent reviews on all-carbon quaternary stereogenic centers, see: a)
J. Christoffers, A. Baro, Adv. Synth. Catal. 2005, 347, 1473-1482; b) B.
M. Trost, C. Jiang, Synthesis 2006, 369-396; c) J. Christoffers, A. Baro,
Quaternary Stereocenters: Challenges and Solutions for Organic
Synthesis, Wiley-VCH, Weinheim, 2006; d) P. G. Cozzi, R. Hilgraf, N.
Zimmermann, Eur. J. Org. Chem. 2007, 5969-5994; d) K. W. Quasdorf,
L. E. Overman, Nature 2014, 516, 181-191; e) I. Marek, Y. Minko, M.
Pasco, T. Mejuch, N. Gilboa, H. Chechik, J. P. Das, J. Am. Chem. Soc.
2014, 136, 2682-2694; f) X. Zeng, Z. Cao, Y. Wang, F. Zhou, J. Zhou,
Chem. Rev. 2016, 116, 7330-7396.
.
[4]
[5]
For reviews on transition metal-catalyzed cyclization reactions, see: a) B.
M. Trost, M. J. Krische, Synlett 1998, 1-16; b) E. Negishi, C. Copéret, S.
Ma, S. Y. Liou, F. Liu, Chem. Rev. 1996, 96, 365-393; c) M. Lautens, W.
Klute, W. Tam, Chem. Rev. 1996, 96, 49-92; d) I. Ojima, M.
Tzamarioudaki, Z. Li, R. J. Donovan, Chem. Rev. 1996, 96, 635-662; e)
C. Aubert, O. Buisine, M. Malacria, Chem. Rev. 2002, 102, 813-834; f) I.
Nakamura, Y. Yamamoto, Chem. Rev. 2004, 104, 2127-2198; g) Y.
Yamamoto, Chem. Rev. 2012, 112, 4736-4769; h) A. Marinetti, H. Jullien,
A. Voituriez, Chem. Soc. Rev. 2012, 41, 4884-4908.
[6]
[7]
a) E. Negishi, M. Jensen, D. Kondakov, S. Wang, J. Am. Chem. Soc.
1994, 116, 8404-8405; b) K. H. Shaughnessy, R. M. Waymouth, J. Am.
Chem. Soc. 1995, 117, 5873-5874; c) D. Kondakov, S. Wang, E. Negishi,
Tetrahedron Lett. 1996, 37, 3803-3806; d) K. H. Shaughnessy, R. M.
Waymouth, Organometallics 1998, 17, 5728-5745; e) Z. Tan, B. Liang,
S. Huo, J. Shi, E. Negishi, Tetrahedron: Asymmetry 2006, 17, 512-515.
a) G. Erker, M. Aulbach, M. Knickmeier, D. Wingbermühle, C. Krürger,
M. Nolte, S. Werner, J. Am. Chem. Soc. 1993, 115, 4590-4601; b) (–)–
(NMI)2ZrCl2 (CAS number: 148347-88-0) and (+)–(NMI)2ZrCl2 (CAS
number: 641627-68-1) are available from Sigma-Aldrich and Wako Pure
Chemicals.
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Entry for the Table of Contents (Please choose one layout)
Layout 2:
COMMUNICATION
Shiqing Xu, Chuan Wang, Masato
Komiyama, Yasuhiko Tomonari, and Ei-
ichi Negishi*
Page No. – Page No.
Asymmetric Synthesis of Chiral
Cyclopentanes Bearing an All-Carbon
Quaternary Stereocenter via
Zr-
catalyzed Doubled Carboalumination
All-carbon quaternary stereocenter: A Zr-catalyzed enantio- and diastereoselective
doubled carboalumination of various unactivated 1,5-dienes has been developed,
providing an efficient access to chiral cyclopentanes with generation of two
stereocenters including an all-carbon quaternary stereocenter through the formation of
two new C–C bonds as well as a C–Al bond in high diastereo- and enantioselectivities.
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