Pd-Catalyzed Enantioselective Ring Opening/Cross-Coupling and Cyclopropanation of Cyclobutanones

Article abstract of DOI:10.1002/anie.201813071

A palladium-catalyzed enantioselective sequential ring-opening/cross-coupling of cyclobutanones is disclosed that provides chiral indanones bearing C3-quaternary stereocenters. The reaction process involves palladium-catalyzed nucleophilic addition of cyc

Full text of DOI:10.1002/anie.201813071

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
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Accepted Article
Title: Pd-Catalyzed Enantioselective Ring-Opening/Cross-Coupling
and Cyclopropanation of Cyclobutanones
Authors: Jian Cao, Ling Chen, Feng-Na Sun, Yu-Li Sun, Ke-Zhi Jiang,
Ke-Fang Yang, Zheng Xu, and Li-Wen Xu
This manuscript has been accepted after peer review and appears as an
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of the final Version of Record (VoR). This work is currently citable by
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201813071
Angew. Chem. 10.1002/ange.201813071
Link to VoR: http://dx.doi.org/10.1002/anie.201813071
http://dx.doi.org/10.1002/ange.201813071

10.1002/anie.201813071
Angewandte Chemie International Edition
COMMUNICATION
Pd-Catalyzed Enantioselective Ring-Opening/Cross-Coupling and
Cyclopropanation of Cyclobutanones
Jian Cao,* Ling Chen+, Feng-Na Sun+, Yu-Li Sun, Ke-Zhi Jiang, Ke-Fang Yang, Zheng Xu, and Li-Wen
Xu*
Abstract: A palladium-catalyzed enantioselective sequential ring-
opening/cross-coupling of cyclobutanones is disclosed, providing
chiral indanones bearing C3-quaternary stereocenters. The reaction
process involves palladium-catalyzed nucleophilic addition of
cyclobutanones and aryl halides, enantioselective β-carbon
elimination[9] can be expected to lead to -alkylpalladium species
containing all-carbon quaternary stereocenters. -
C
Alkylpalladium species, usually formed via enantioselective
intramolecular carbopalladation of alkenes, have become
versatile intermediates for creating quaternary stereocenters
owing to the endeavor of the groups of Zhu,[10] Jia,[11] Diaz,[12]
and Zhang.[13] We anticipate the -alkylpalladium species
generated through ring-opening of cyclobutanones would be
trapped by various nucleophiles to produce indanones bearing
elimination and intermolecular trapping of
a
transient -
alkylpalladium complex with boronic acids. Alternatively, an
intramolecular cyclopropanation is realized via C-H bond
functionalization in the absence of external coupling reagents,
affording chiral cyclopropane-fused-indanones in good yields and
enantioselectivity.
C3-quaternary stereocenters. Alternatively,
a
C(sp3)−C(sp3)
bond could be forged via intramolecular C-H functionalization in
the absence of external nucleophiles, thus leading to chiral
cyclopropane-fused-indanones.[14]
Chiral
indanones
and
Quaternary carbon stereocenters, bonded by four different
carbon substituents, are omnipresent in natural products and
pharmaceuticals. Catalytic enantioselective creation of
quaternary stereocenters is a long-term challenge.[1] In this
respect, enantioselective desymmetrization of prochiral small-
ring compounds has emerged as a powerful tool for creating
cyclopropane-fused-cyclopentane skeletons are important
structural units in many natural products and pharmaceuticals.[15]
quaternary
carbon
stereocenters.[2]
For
example,
enantioselective desymmetrization of prochiral cyclobutanones
via Rh- and Ni-catalyzed ring-opening and ring-expansion has
been achieved by the groups of Murakami,[3] Cramer,[4] and
Dong.[5] In addition, Pd-catalyzed racemic ring-opening and ring-
expansion reaction patterns of cyclobutanones were established
by Murakami with achiral catalyst systems.[6] Recently, Lu
reported a Pd-catalyzed asymmetric intramolecular α-arylation of
prochiral cyclobutanones and aryl halides, forming chiral
cyclobutanones containing quaternary carbon stereocenters
(Scheme 1A).[7] Herein, we disclose an enantioselective Pd-
catalyzed tandem ring-opening/carbon-carbon bond forming
reaction pattern between prochiral cyclobutanones and aryl
halides (Scheme 1B). Our strategy is based on the proposed
enantioselective ring-opening process: arylpalladium species A
generated via oxidative addition of symmetrical cyclobutanones
with palladium catalysts would undergo nucleophilic addition
toward carbonyl group to form alkoxypalladium intermediate B.[8]
With appropriate chiral ligands, enantioselective β-carbon
Scheme 1. Pd-catalyzed enantioselective desymmetrization of prochiral
cyclobutanones with aryl halides.
To achieve this proposal, the following issues need to be
addressed: (1) The critical step nucleophilic addition (A to B)
requires effective carbonyl-palladium coordination to avoid
direct cross-coupling, therefore judicious choices of bulky
monodentate phosphine ligands capable of leaving a vacant
orbital of palladium is a prerequisite. (2) At the chirality-
determining step (B to C), appropriate chiral, and at the same
time bulky monodentate phosphine ligands are required to
achieve both high enantioselectivity and good chemoselectivity.
(3) It is nontrivial to identify two sets of reaction conditions to
achieve competitive intermolecular capture and intramolecular
C-H functionalization respectively.
[*]
Dr. J. Cao, L. Chen,[+] F.-N. Sun,[+] Y.-L. Sun, Dr. K.-Z. Jiang, Dr. K.-
F. Yang, Dr. Z. Xu, Prof. Dr. L.-W. Xu
Key Laboratory of Organosilicon Chemistry and Material Technology
of Ministry of Education, Hangzhou Normal University, No. 2318,
Yuhangtang Road, 311121, Hangzhou, P. R. China
E-mail: caojian@hznu.edu.cn (CJ) and liwenxu@hznu.edu.cn (XLW)
Prof. Dr. L.-W. Xu
Suzhou Research Institute and State Key Laboratory for Oxo
Synthesis and Selective Oxidation, Lanzhou Institute of Chemical
Physics, Chinese Academy of Sciences, 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.201813071
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COMMUNICATION
Initially, aryl boronic acids were selected as the
nucleophiles to examine the feasibility of ring-opening/cross-
coupling sequence since Suzuki-Miyaura coupling has become
one of the most robust methods for the construction of carbon-
carbon bonds. 3-(2-Bromophenyl)-3-methylcyclobutanone 1a
and 4-methoxyphenyl-boronic acid were used as the model
substrates. After a systematic survey of reaction parameters
(Table S1 in supporting information), the following optimum
conditions were identified: Pd2(dba)3 (0.05 equiv), XPhos (0.1
equiv), K2CO3 (2.5 equiv), 1,4-dioxane, 100 oC, affording the
desired 1-indanone 2a in 89% yield and direct cross-coupling
product 3a [Eq. (1)]. It should be noted that the cyclopropanation
product 4a was also observed albeit in trace amounts.
as the model substrate. Under the optimum conditions for ring-
opening/Suzuki-Miyaura reaction in the absence of boronic acid,
the desired cyclopropanantion product 4a was obtained in only
9% yield and significant amount of substrate 1a remained intact,
suggesting the difficulty of formation of three-membered ring
(Table 1, entry 1). After extensive screening of reaction
parameters, we found that addition of one equivalent of
Brønsted acids (e.g. TsOH, entry 2) greatly increased the yield.
Further screening led to the finding that simply replacing the
base K2CO3 with KHCO3 without additional acids resulted in
excellent yield (entry 3). Subsequently, a set of chiral ligands
were screened for achieving enantioselective cyclopropanation.
Among the screened phosphine ligands, TADDOL-derived
phosphoramidites showed promising level of enantioselectivity
and L12 proved to be most effective (entries 4-8). Lowering the
o
reaction temperature to 90 C increased the yield to 94% and
enantiomer ratio to 97.5:2.5 (entry 9, for detailed screening of
other parameters, see Table S3 in supporting information).
Table 1. Optimization of the enantioselective ring-opening/cyclopropanation.[a]
Subsequently, a range of chiral monodentate phosphine
ligands were examined to realize the enantioselective sequential
reaction. Among the screened phosphine ligands, BINOL- and
TADDOL-derived phosphoramidites[16] showed promising level
of enantioselectivity and selected examples were shown in
Scheme 2 (for screening of other parameters, see Table S2 in
supporting information). While BINOL-derived phosphoramidites
L1-L3 resulted in only moderate enantioselectivity, new
TADDOL-derived phosphoramidites L7 and L8 proved to be
suitable, giving good yield and enantioselectivity. Thus L8 was
chosen as the optimized chiral ligand for subsequent evaluation
of the generality of this enantioselective reaction.
Entry
Ligand
XPhos
XPhos
XPhos
L4
Base
Yield [%]
er
1
K2CO3
9
/
[Pd(allyl)Cl]2 (2.5 mol%)
O
L (10 mol%)
Ar
+
ArB(OH)2
2
K2CO3 + TsOH
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
49
96
94
92
96
94
91
94
/
Ag2CO3 (2.5 equiv)
dioxane
Br
1a
80 o
C
O
3
/
2a
Ar = 4-MeOC6H4
4
66:34
90:10
89:11
87.5:12.5
96.5:3.5
97.5:2.5
Ph
N
Ph
N
Et
Et
O
O
O
O
O
O
5
L9
P
N
P
P
Ph
Ph
6
L10
L1 (R)
19%, 73:27 er
L2 (S,R,R)
35%, 65.5:34.5 er
L3 (S,S,S)
34%, 77:23 er
7
L11
Ar'
Ar'
Ph
Ph
Ar'
Ar'
8
L12
O
P
O
O
O
P
O
O
P N
O
O
O
O
Et
Et
R
R
N
N
R
9[b]
L12
O
O
Ph
Ar'
Ph
Ar'
Ar'
Ph
Ar'
[a] Unless otherwise specified, the reactions were run on 0.2 mmol scale in 2 mL
solvents at 100 oC for 24 h. [b] The reaction was run at 90 oC
L4 (R,R) R = Me
L6 (R,R) R = Me
L8 (R,R)
31%, 44.5:55.5 er
42%, 86:14 er
91%, 93.5:6.5 er
L5 (R,R) R = Ph
11%, 62.5:37.5 er
L7 (R,R) R = Et
90%, 93:7 er
Ar' = 3,5-Me2C6H3
With the two sets of optimum conditions in hand, the scope
and limitation of these enantioselective ring-opening/carbon-
carbon bond forming reactions was examined. As depicted in
Scheme 3, a wide variety of boronic acids proved to be
amenable to this transformation. Aryl boronic acids bearing both
electron-donating and -withdrawing groups regardless of their
positions participated efficiently to afford the desired products
2a-2l. Functional groups including methoxy, methylthio, fluorine,
Scheme 2. Selected screening of chiral ligands for tandem ring-
opening/cross-coupling reaction.
At the same time, the highly strained cyclopropanation
product 4a attracted our interest. Thus we next examined this
tandem ring-opening/cyclopropanation using cyclobutanone 1a
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10.1002/anie.201813071
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COMMUNICATION
chlorine, trifluoromethoxy, and ester were well tolerated. In
addition, an alkenyl group could also be easily incorporated in
the product 2m. On the other hand, the scope of cyclobutanones
was also screened. Cyclobutanones bearing various alkyl
groups at the R1 position are compatible (2n-2q). Although the
product 2x with a phenyl group at R1 position can be obtained in
67% yield under racemic conditions, enantioselective reaction
only gave the desired product in trace amount. When R1 was H,
the desired product was not found and only direct Suzuki-
Miyaura coupling product was obtained. Substituents on the
phenyl moiety of cyclobutanones, including halogen and
methoxy, were well tolerated, leaving ample room for further
functionalization (2d, 2r-2v). Generally, enantiomeric ratio
ranged from 93:7 to 97.5:2.5. The absolute configurations of 2f
and 2v were disclosed by X-ray diffraction analysis.[17] To
demonstrate the practicability of our protocol, a gram-scale
experiment (8 mmol) was conducted and 2a was obtained in
excellent yield and good enantioselectivity.
Scheme 4. Reaction scope of the enantioselective tandem ring-
opening/cyclopropanation.
A
plausible mechanism was proposed for these
enantioselective tandem ring-opening/carbon-carbon bond
forming reactions.[18] As outlined in Scheme 5, symmetrical
cyclobutanones
1
undergo oxidative addition to form
arylpalladium species A. Subsequent nucleophilic addition of
arylpalladium toward carbonyl group in cyclobutanones
generates highly strained alkoxypalladium intermediate B. With
appropriate chiral ligands, enantioselective -carbon elimination
leads to -alkylpalladium species C. Intramolecular C-H bond
functionalization affords the cyclopropanation product 4 via
palladacyclobutane intermediate D (path a). Alternatively, -
alkylpalladium species C is captured by boronic acids to form
intermediate E (path b), which gives 1-indanone 2 through
reductive elimination.
Scheme 3. Reaction scope of the enantioselective ring-opening/cross-
coupling. [a] 8 mmol scale. Ar = 4-MeOC6H4, Ar' = 4-(MeOCO)C6H4. [b] Under
racemic conditions in Eq 1.
Next, the scope and limitation of the enantioselective ring-
opening/cyclopropanation was examined with
a variety of
cyclobutanones. As shown in Scheme 4, alkyl groups were well
tolerated at R1 position, delivering the expected products 4a-4e.
Phenyl was also amenable albeit with lower enantioselectivity
(4f). Unfortunately, no reaction occurred when R1 was H.
Cyclobutanones with functional groups on the phenyl moiety,
such as Cl, F, and MeO, afforded the desired products 4g-4m in
good yields and enantioselectivity. The absolute configuration of
4m was disclosed by X-ray diffraction analysis.[17]
Scheme 5. Proposed mechanism.
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COMMUNICATION
[1]
For recent reviews, see: a) K. W. Quasdorf, L. E. Overman, Nature 2014,
516, 181; b) Y. Liu, S.-J. Han, W.-B. Liu, B. M. Stoltz, Acc. Chem. Res.
2015, 48, 740.
Since halogens Cl and F were well tolerated, various cross-
coupling technologies can be considered for downstream
derivatization. For example, 2w obtained from 1a under
standard conditions smoothly underwent Pd-catalyzed α-
[2]
[3]
X.-P. Zeng, Z.-Y. Cao, Y.-H. Wang, F. Zhou, J. Zhou, Chem. Rev. 2016,
116, 7330.
arylation to afford polycyclic product
5
as the sole
a) T. Matsuda, M. Shigeno, M. Makino, M. Murakami, Org. Lett. 2006, 8,
3379; b) T. Matsuda, M. Shigeno, M. Murakami, J. Am. Chem. Soc.
2007, 129, 12086; c) L. Liu, N. Ishida, M. Murakami, Angew. Chem. Int.
Ed. 2012, 51, 2485; Angew. Chem. 2012, 124, 2535.
diastereoisomer (Scheme 6). The relative configuration of 5 was
deduced by NOESY spectrum (see supporting information). The
fluorine atom in 2v could be easily replaced by an amine via
nucleophilic aromatic substitution to form 6. In addition, the
versatile carbonyl group was transferred to carbon-carbon
double bond, delivering chiral indene 7 through 2 steps. It should
be noted that all the derivatives were obtained without
racemization.
[4]
[5]
[6]
a) E. Parker, N. Cramer, Organometallics 2014, 33, 780; b) L. Souillart,
E. Parker, N. Cramer, Angew. Chem. Int. Ed. 2014, 53, 3001; Angew.
Chem. 2014, 126, 3045; c) L. Souillart, N. Cramer, Angew. Chem. Int.
Ed. 2014, 53, 9640; Angew. Chem. 2014, 126, 9794.
a) X. Zhou, G. Dong, Angew. Chem. Int. Ed. 2016, 55, 15091; Angew.
Chem. 2016, 128, 15315; b) X. Zhou, G. Dong, J. Am. Chem. Soc.
2015, 137, 13715; c) H. M. Ko, G. Dong, Nature Chemistry 2014, 6,
739.
Cl
OMe
Me
standard
conditions
Pd2(dba)3
XPhos
Me
a) T. Matsuda, M. Shigeno, M. Murakami, Org. Lett. 2008, 10, 5219. For
other racemic Pd-catalyzed ring-opening and ring-expansion of
cyclobutanones, see: b) N. Ishida, W. Ikemoto, M. Murakami, Org. Lett.
2012, 14, 3230; c) N. Ishida, W. Ikemoto, M. Murakami, J. Am. Chem.
Soc. 2014, 136, 5912.
1a
+
OMe
K3PO4
H
OMe
Cl
dioxane
90 o
C
O
B(OH)2
O
2w
5
78%, 96:4 er
73%, 95.5:4.5 er
Me
O
Me
[7]
[8]
M. Wang, J. Chen, Z. Chen, C. Zhong, P. Lu, Angew. Chem. Int. Ed.
2018, 57, 2707; Angew. Chem. 2018, 130, 2737.
O
F
N
DMSO
+
120 o
C
OMe
N
H
OMe
For Pd-catalyzed nucleophilic addition of aryl halides to ketones, see: a)
L. G. Quan, V. Gevorgyan, Y. Yamamoto, J. Am. Chem. Soc. 1999,
121, 3545; b) V. Gevorgyan, L. G. Quan, Y. Yamamoto, Tetrahedron
Lett. 1999, 40, 4089; c) L. G. Quan, M. Lamrani, Y. Yamamoto, J. Am.
Chem. Soc. 2000, 122, 4827; d) J. Vicente, J.-A. Abad, B. López-
Peláez, E. Martínez-Viviente, Organometallics 2002, 21, 58; e) D. Solé,
L. Vallverdú, X. Solans, M. Font-Bardía, J. Bonjoch, J. Am. Chem. Soc.
2003, 125, 1587; f) Y. B. Zhao, B. Mariampillai, D. A. Candito, B. Laleu,
M. Z. Li, M. Lautens, Angew. Chem. Int. Ed. 2009, 48, 1849; Angew.
Chem. 2009, 121, 1881.
O
O
6
2v
74%, 95.5:4.5 er
Me
1) TsNHNH2, MeOH
60 oC, 77%
Me
OMe
2) 4-Me2NC6H4Br
Pd2(dba)3, XPhos
tBuOLi, dioxane
120 oC, 79%
OMe
O
NMe2
7
2a
96:4 er
[9]
For enantioselective β-carbon elimination of palladium(II)-alcoholate
species, see: a) T. Nishimura, S. Matsumura, Y. Maeda, S. Uemura,
Chem. Commun. 2002, 50; b) S. Maysumura, Y. Maeda, T. Nishimura,
S. Uemura, J. Am. Chem. Soc. 2003, 125, 8862; c) A. Ziadi, A. Correa,
R. Martin, Chem. Commun. 2013, 49, 4286.
Scheme 6. Synthetic applications.
In conclusion, we developed
a
tandem nucleophilic
[10] a) A. Pinto, Y. Jia, L. Neuville, J. Zhu, Chem. Eur. J. 2007, 13, 961; b) W.
Kong, Q. Wang, J. Zhu, J. Am. Chem. Soc. 2015, 137, 16028; c) W.
Kong, Q. Wang, J. Zhu, Angew. Chem. Int. Ed. 2016, 55, 9714; Angew.
Chem. 2016, 128, 9866; d) W. Kong, Q. Wang, J. Zhu, Angew. Chem.
Int. Ed. 2017, 56, 3987; Angew. Chem. 2017, 129, 4045; e) X. Bao, Q.
Wang, J. Zhu, Angew. Chem. Int. Ed. 2017, 56, 9577; Angew. Chem.
2017, 129, 9705; f) S. Tong, A. Limouni, Q. Wang, M.-X. Wang, J. Zhu,
Angew. Chem. Int. Ed. 2017, 56, 14192; Angew. Chem. 2017, 129,
14380.
addition/β-carbon elimination paradigm between cyclobutanones
and intramolecular aryl halides, generating -alkylpalladium
species bearing β-quaternary carbon stereocenters. Using
boronic acids as external nucleophilic trapping reagents, the
enantioselective domino ring-opening/cross-coupling reaction
was achieved for the construction of 1-indanones bearing C3-
quaternary
stereocenters.
In
addition,
a
ring-
opening/cyclopropanation sequence was realized in the absence
of external nucleophiles, affording chiral cyclopropane-fused-
indanones in good yields and enantioselectivity.
[11] a) C. Shen, R.-R. Liu, R.-J. Fan, Y.-L. Li, T.-F. Xu, J.-R. Gao, Y.-X. Jia,
J. Am. Chem. Soc. 2015, 137, 4936; b) R.-R. Liu, Y.-G. Wang, Y.-L. Li,
B.-B. Huang, R.-X. Liang, Y.-X. Jia, Angew. Chem. Int. Ed. 2017, 56,
7475; Angew. Chem. 2017, 129, 7583.
[12] P. Diaz, F. Gendre, L. Stella, B. Charpentier, Tetrahedron 1998, 54,
4579.
Acknowledgements
[13] Z.-M. Zhang, B. Xu, Y. Qian, L. Wu, Y. Wu, L. Zhou, Y. Liu, J. Zhang,
Angew. Chem. Int. Ed. 2018, 57, 10373; Angew. Chem. 2018, 130,
10530.
Financial support from National Natural Science Foundation of
China (No. 21472031) and Zhejiang Provincial Natural Science
Foundation of China (No. LY18B020013 and LZ18B020001) is
gratefully acknowledged.
[14] For examples of racemic Pd-catalyzed cyclopropanation via C-H
functionalization, see: W. Du, Q. Gu, Z. Li, D. Yang, J. Am. Chem. Soc.
2015, 137, 1130.
[15]
a) T. Lomberget, E. Bentz, D. Bouyssi, G. Balme, Org. Lett. 2003, 5,
2055; b) T. Ito, T. Tanaka, M. Iinuma, K. Nakaya, Y. Takahashi, R.
Sawa, J. Murata, D. Darnaedi, J. Nat. Prod. 2004, 67, 932; c) E. Fillion,
D. Fishlock, A. Wilsily, J. M. Goll, J. Org. Chem. 2005, 70, 1316; d) G.
Yue, L. Yang, C. Yuan, X. Jiang, B. Liu, Org. Lett. 2011, 13, 5406.
Keywords: Cyclobutanone • C-C activation • quaternary
stereocenter • asymmetric catalysis • palladium-catalysis
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10.1002/anie.201813071
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COMMUNICATION
[16]
For selected reviews on TADDOL-derived phosphoramidites ligands,
see: a) B. L. Feringa, Acc. Chem. Res. 2000, 33, 346; b) J. F. Teichert,
B. L. Feringa, Angew. Chem. Int. Ed. 2010, 49, 2486; Angew. Chem.
2010, 122, 2538; c) J. Pedroni, N. Cramer, Chem. Commun. 2015, 51,
17647.
[17] CCDC 1816797, 1816798 and 1840312 contain the supplementary
crystallographic data for this paper (2f, 2v and 4m). These data are
provided free of charge by The Cambridge Crystallographic Data
Centre.
[18] The ring-opening/cyclopropanation reaction was monitored by in-situ IR,
NMR, GC-MS and HRMS. See supporting information.
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Entry for the Table of Contents (Please choose one layout)
Layout 2:
COMMUNICATION
Jian Cao,* Ling Chen, Feng-Na Sun, Yu-
Li Sun, Ke-Zhi Jiang, Ke-Fang Yang,
and Zheng Xu, Li-Wen Xu*
R3B(OH)2
[Pd(allyl)Cl]2/L*
Ag2CO3
1,4-dioxane, 80 o
Pd2(dba)3/L*
KHCO3
R1
R1
R1
R3
1,4-dioxane, 90 o
C
C
O
R2
R2
R2
Ar
Ar
O
O
Ph
Ph
O
O
H
Br
iPr
Bn
O
O
Et
Et
Page No. – Page No.
L*:
L*:
P
O
N
P
N
22 examples
13 examples
up to 96% yield
up to 98:2 er
O
O
O
up to 91% yield
up to 97.5:2.5 er
Ar
Ph
Ph
Ar
Pd-Catalyzed Enantioselective Ring-
Opening/Cross-Coupling and
Cyclopropanation of Cyclobutanones
Ar: 3,5-Me2C6H3
Enantioselective desymmetrization of prochiral cyclobutanones is realized via
tandem palladium-catalyzed ring-opening/cyclopropanation, providing chiral
cyclopropane-fused-indanones. With external coupling reagents, the transient σ-
alkylpalladium intermediate can be captured to afford an array of chiral indanones
bearing C3-quaternary stereocenters.
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