Asymmetric H2O-Nucleophilic Ring Opening of D-A Cyclopropanes: Catalyst Serves as a Source of Water

Article abstract of DOI:10.1021/jacs.5b10310

The first catalytic enantioselective ring-opening reaction of donor-acceptor cyclopropanes with water is described. By employing Cy-TOX/Cu(II) as catalyst, the reaction performed very well over a broad range of substrates, leading to the ring-opening products in 70-96% yields with up to 95% ee under mild conditions. The current method provides a new approach to direct access to γ-substituted GBH derivatives very efficiently. Importantly, Cu(ClO₄)₂·6H₂O proves to serve as both a Lewis acid and a source of water, which affords a fine system to controllably release water as a nucleophile in the asymmetric catalysis.

Full text of DOI:10.1021/jacs.5b10310

Subscriber access provided by Stockholm University Library
Communication
Asymmetric H2O-Nucleophilic Ring-opening of D-
A Cyclopropanes: Catalyst Serves as a Source of Water
Qi-Kai Kang, Lijia Wang, Qiong-Jie Liu, Jun-Fang Li, and Yong Tang
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.5b10310 • Publication Date (Web): 05 Nov 2015
Downloaded from http://pubs.acs.org on November 7, 2015
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
Journal of the American Chemical Society is published by the American Chemical
Society. 1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 6
Journal of the American Chemical Society
1
2
3
4
5
6
Asymmetric H O-Nucleophilic Ring-opening of D-A Cyclopropanes:
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
2
Catalyst Serves as a Source of Water
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
†
†
†
†
,
†,‡
QiꢀKai Kang, Lijia Wang, QiongꢀJie Liu, JunꢀFang Li, Yong Tang*
†
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 345 Lingling Lu, Shanghai 200032, China
‡
Collaborative Innovation Center of Chemical Science and Engineering (Tianjin)
Supporting Information Placeholder
cyclopropane 1a, and tested 5.0 equivalents of benzyl alcohol
2
reaction under the standard conditions. Unfortunately, the
desired product was not observed in DME. Thus, we turned
to
ABSTRACT: The first catalytic enantioselective ring-opening
a as nucleophile instead of amine to run the ring-opening
reaction of D-A cyclopropanes with water is described. By
employing Cy-TOX/Cu(II) as catalyst, the reaction per-
formed very well over a broad range of substrates, leading to
the ring opening products in 70-96% yields with up to 95%
ee under mild conditions. The current method provides a
new approach to direct access to γ-substituted GBH deriva-
tives very efficiently. Importantly, Cu(ClO ) ∙6H O proves to
other
catalyst
system
and
found
that
Cu(OTf) /bisoxazoline (BOX) could promote this reaction
2
(Table 1). After optimizing the solvents, Lewis acids, the ester
groups, we screened various BOX ligands and found that Cy-
BOX L1 gave 80% ee in 87% yield (entry 1). Further study
showed the sidearm (SA) on the bridge carbon of BOX also
influenced the results.
4
2
2
serve as both a Lewis acid and a source of water, which af-
fords a fine system to controllable release water as a nucleo-
phile in the asymmetric catalysis.
a
Table 1. Optimization of Reaction Conditions.
Owing to their flexible reaction patterns and versatile ap-
proaches for further elaboration of the products, donor-
acceptor (D−A) cyclopropanes are considered as useful syn-
thetic building blocks and have attracted increasing atten-
1
tion of synthetic chemists in recent years. Asymmetric ring-
2
opening annulations have been well studied and successfully
applied in the total synthesis of natural products and biologi-
cally active molecules. Many reports on the direct nucleo-
o
b
entry
SA/L
T( C) yield(%)
ee
3
c
(
%)
philic ring opening reactions of D−A cyclopropanes ap-
2-4
1
H/L1
40
40
40
40
40
40
87
81
80
84
82
86
81
87
peared, however, no successful examples on their asym-
metric versions are described except that the enantioselec-
tive ring-opening reactions of D−A cyclopropanes with sec-
2
3
4
5
6
Ph/L2
t
5
3,5- Bu
2
C
6
H
3
/L3
65
82
74
82
ondary amines and indoles. As our ongoing research on the
asymmetric ring-opening of D-A cyclopropanes, we are in-
3,5-(OCH
) C H /L4
3 2 6 3
6
terested in developing asymmetric reaction of H O with D-
2
3,4,5-(OCH ) C H /L5
3
3
6
3
A cyclopropanes, a potential approach to optically active
7
GHB acid derivatives. In the past several years, it proves very
challenging since water is a weak nucleophile and the corre-
sponding product alcohol is more nucleophilic than water,
which leads to competing by-products in the ring opening
reaction. In addition, water in the reaction system can nor-
mally poison the Lewis acid catalyst and slow down the reac-
/L6
7
40
89
85
/
L7
8
8
9
40
0
88
87
90
89
93
93
tion. In this communication, we wish to report a novel
/
L8
L8
/L8
strategy by employing catalyst as a source of water to realize
the asymmetric ring opening reactions of D−A cyclopropanes
with water.
/
d
Initially, we tried several Lewis acids as catalysts for the
water ring-opening reaction of D−A cyclopropane 1a but
failed. In order to shed light on this ring-opening reaction,
we chose alcohol as a model substrate instead of water for
the initial study. We first employed In-TOX/Ni(ClO ) as the
10
0
a
Conditions: All reactions were carried out under Ar at-
mosphere, 1a (0.44 mmol), 2a (0.20 mmol), Cu(OTf) (0.020
2
4
2
mmol), L (0.024 mmol) in C H F (2.0 mL) and 4 Å MS (200
6
5
catalyst, which is optimal in the reaction of amine with D−A
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 6
b
c
d
mg). Isolated yield based on 2a. Determined by chiral
Determined by chiral HPLC. At 40 °C.
d
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
HPLC. In C H F (0.4 mL) and 4 Å MS (40 mg).
6
5
Inspired by the success of the asymmetric ring-opening re-
action with alcohol, we next reinvestigated water as nucleo-
phile in an effort to obtain the corresponding GHB diesters
directly. Based on the former scrupulous evaluation, we em-
As shown in Table 1, 84% ee could be obtained by in-
stalling phenyl as a side arm (entry 2) and substituted phenyl
further improved the enantiomeric excess to 87% (entries 3-
9,10
ployed Cu(OTf) /Cy-TOX as the catalyst and treated racemic
7). Finally, cyclohexyl−trisoxazoline
(Cy−TOX) L8 was
2
D−A cyclopropane 1a with 5.0 equivalents of water as nucle-
found to give the optimal result. In this case, the desired ring
opening product 3a was obtained in 88% yield with 89% ee
o
ophile in fluorobenzene at 40 C. Fortunately, the ring open-
ing product 4a was obtained with 89% ee but in only 9%
yield (entry 1, Table 3). As tabulated in Table 3, the solvents
influence the reaction strongly. For example, the reaction did
not occur in toluene (entry 2). When THF was used, the yield
was improved to 29% (entry 3). With dimethoxyethane
in the presence of 10 mol% L8/Cu(OTf) (entry 8). Lowering
2
o
the reaction temperature to 0 C, combined with increasing
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
the substrate concentration, the desired product was resulted
in 90% yield with 93% ee (entry 10).
The current catalyst system was found insensitive to the
structure of the nucleophiles. When the reactions were per-
formed using benzyl alcohol 2a, the reaction proceeded
smoothly to furnish product 3a-3c in high yields with good to
excellent levels of enantioselectivity (90-96% ee, Table 2,
entries 1-3), not only for the cyclopropanes with both elec-
tron donating and electron withdrawing groups on the phe-
nyl substituents, but also for those substituted with 2-thienyl
groups, which are flexible for further transformation in or-
ganic synthesis. Since the benzyl group could be readily re-
moved, this process provided a synthetic useful approach to
a variety of enantio-enriched substituted GHB diesters. Un-
saturated alcohols, such as cinnamyl alcohol and propargyl
alcohol, both reacted with high enantioselectivity (93-94%
ee, entries 4-5). The ring-opening reaction also worked well
with 1-octanol 2d, giving the target products 3f in 79% yield
with 94% ee (entry 6). Functionalized alcohol 2e derived
from ethylene glycol was well-tolerated in the current sys-
tem, affording the corresponding γ-alkoxy butyric diester 3g
in 73% yield with 93% ee (entry 7). In particular, the ring
opening with secondary alcohol 2f proceeded very well,
providing the desired product 3h in 80% yield with 94% ee
(
DME, containing 230 ppm of water) as solvent, the desired
product 4a was afforded in 23% yield with 92% ee (entry 4).
Remarkably, it was found that the amount of water in this
reaction proved critical (Scheme 1). When it was conducted
without additional water, the reaction could also occur, af-
fording the product 4a in 34% yield with 90% ee (eq.2). In
this case, the D−A cyclopropane 1a was all consumed and a
product-initiated nucleophilic ring opening by-product 5 was
isolated as a main by-product. These results suggested that
product 4a can further nucleophilic attack the D−A cyclo-
propane 1a even faster than water in the reaction system,
which is a major competitor of water for the ring-opening
process and will destroy the desired product 4a. We strug-
gled to improve the yield and found that the reaction was
sluggish with additional 5.0 equivalents of water. Only 23%
yield was obtained with a big surplus of cyclopropane, and
no by-product was detected, probably due to the reason that
the excessive amount of water poisoned the Lewis acid and
deteriorated the effective activation of the D−A cyclopropane
(eq.1). We also tested addition of 4Å molecule sieves to re-
move the water in the system, but it led to no reaction (eq.
3). Hundreds of attempts failed and higher than 40% yields
proved to be a challenging task. As the amount of water af-
fected the reaction clearly, we conceived that keeping the
water at a proper concentration may suppress both the com-
peting coordination and the undesired alcohol nucleophilic
ring opening reaction. Further screening carefully on the
water loading (Figure 1, for details, see SI) revealed that the
yield of 4a could reach a slightly varied level in a range of 74-
(
entry 8).
Table 2. Substate Scope using Alcohol as Nucleo-
a
phile.
7
8% with the ee values remained in 91-92% when the water
1
2
b
c
12
entry R
R (2)
3/yield(%) ee(%)
was added in a range of 0.5-1.0 equiv. However, the protocol
by direct adding water to the reaction system suffered a ma-
jor setback due to the inconvenient experimental operation
and the unreproducible yields. Inspired by these results, we
tested crystalline hydrate of catalyst as a reservoir to control
and release water. It was found that the product 4a was fur-
nished in 71% yield with 89% ee (entry 5, Table 3; eq. 4,
Scheme 1) when Cu(ClO ) ∙6H O was employed. Although 5
1
4-MeOC H4 Bn (2a)
3a /90
3b /89
3c /92
3d /92
3e /70
3f /79
93
96
90
94
93
94
6
d
2
3
4-BrC H4
Bn (2a)
Bn (2a)
6
2-thienyl
4
5
6
4-MeOC H4 cinnamyl (2b)
6
4-MeOC H4 propargyl (2c)
6
4
2
2
mol % of the Cu(ClO ) ∙6H O could lead to 57% yield (entry
4
2
2
4-MeOC H4 n-octyl (2d)
6
6
), 15 mol% of the Cu(ClO ) ∙6H O gave the desired product
4 2 2
4
-MeOC H4 TBSOCH CH
6 2 2
in 92% yield and 90% ee (entry 7). Further lowering the reac-
tion temperature from 40 to 25 °C, the yield was improved to
95% with 93% ee (entry 8) in the case of L8/Cu(ClO ) ∙6H O
4 2 2
as the catalyst. In the presence of 4 Å MS, the desired prod-
uct was not observed (entry 9).
7
3g /73
3h /80
93
94
(
2e)
i
8
4-MeOC H4 Pr (2f)
6
a
Conditions: All reactions were carried out under Ar
o
atmosphere at 0 C, 1 (0.44 mmol), 2 (0.20 mmol),
Cu(OTf) (0.020 mmol), L8 (0.024 mmol) in C H F (0.4
mL) and 4 Å MS (40 mg). Isolated yield based on 2.
a
Table 3. Optimization of Reaction Conditions.
2
6
5
b
c
ACS Paragon Plus Environment

Page 3 of 6
Journal of the American Chemical Society
CO (2ꢀAd)
OH CO (2ꢀAd)
2
In order to trace the source of the hydroxyl oxygen in the
ring opening product, an isotropic labeling experiment was
2
1
0 mol% L8/Cu(II)
1
CO (2ꢀAd)
2 + H
2
O
PMP
2
CO (2ꢀAd)
solvent, 40 o
C
18
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
PMP
conducted by using Cu(ClO
)
∙6H
O
instead of
1a
4a
4
1
2
2
8
18
Cu(ClO ) ∙6H O. As expected, 66 O% of the 4a- O was
4
2
2
1
1
obtained. This result demonstrated that Cu(ClO ) ∙6H O
4
2
2
entry
Cu(II)
solvent
water
equiv.) (%)
yield ee
b
c
plays dual roles both as the catalyst and a source of water for
the ring-opening reaction.
(
(%)
1
Cu(OTf)2
PhF
5.0
5.0
5.0
5.0
0
9
89
2
CO (2ꢀAd)
5 mol% L8/Cu(ClO ) —6H218O
18OH CO (2ꢀAd)
2
1
4
2
2
3
4
5
Cu(OTf)2
PhMe
THF
DME
-
-
2
CO (2ꢀAd)
PMP
CO (2ꢀAd)
4 O
2
Cu(OTf)2
29
23
71
57
92
95
0
91
92
89
90
90
93
-
PMP
DME, rt
a-18
1a
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Cu(OTf)2
91% yield, 66 18
O%
Cu(ClO ) ∙6H O DME
4
2
2
d
6
Cu(ClO ) ∙6H O DME
0
To examine the generality of this strategy, we studied the
scope of the enantioselective ring opening reacion (Table 4).
D−A cyclopropanes with substituents containing various
alkoxy and acyl amino groups on the phenyl ring all reacted
smoothly with excellent enantioselectivity (70-95% yields,
4
2
2
e
7
Cu(ClO ) ∙6H O DME
0
4
2
2
e,f
8
Cu(ClO ) ∙6H O DME
0
4
2
2
g
9
Cu(ClO ) ∙6H O DME
0
4
2
2
1
1,12
a
90-95% ee, 4a-4e). The current catalyst system can also be
applied to substrates bearing cinnamyl and substituted cin-
namyl groups, providing the corresponding products 4f-4g in
good to high yields with high levels of enantioselectivity.
Notably, these classes of products would be generally diffi-
cult to prepare by traditional carbonyl reduction methods
due to the sensitive carbon-carbon double bonds. Further-
more, heterocyclic substrate such as 2-(2-thienyl) cyclopro-
pane 1,1-diesters was well tolerated (4h). Notably, 3-indolyl
substituted cyclopropanes with both electron-donating and
electron-withdrawing groups could resulted in 70-96% yields
with 82-88% ee (4i-4k). Notably, the current reaction is easi-
ly scaled up. As shown in Table 4, 85% yield was obtained
with 92% ee when 2 mmol of 1a was employed. Lowing the
catalyst loading to 5 mol% on gram-scale reaction, 79% yield
of the desired product (830 mg) was afforded without loss of
Conditions: All reactions were carried out under Ar at-
mosphere, 1a (0.20 mmol), metal (0.020 mmol), L8 (0.024
mmol) in solvent (1.0 mL). Isolated yield based on 1a. De-
termined by chiral HPLC. With 5 mol% catalyst loading.
With 15 mol% catalyst loading, in 2.0 mL of DME. At room
b
c
d
e
f
g
temperature. 4 Å MS (200 mg).
Scheme 1. Effects of the Water Loading.
OH CO (2ꢀAd)
2
(
30% conv.)
H O (5.0 equiv)
PMP
CO (2ꢀAd)
2
2
4
a
(1)
10 mol% cat., DME
2
3 % yield, 92% ee
(
>99% conv.)
10 mol% cat., DME
O free"
1
2
the enantiopurity.
4a 34 % yield, 90% ee
"
H
2
CO
2
(2ꢀAd)
(2ꢀAd)
+
In conclusion, we have developed a new strategy that the
hydrate copper serves as both a Lewis acid and a source of
CO
2
PMP
(
(
2
Adꢀ2)O C
O
(
2)
PMP
1a
nucleophile in the first H O-nucleophilic enantioselective
2
2
Adꢀ2)O C
PMP
CO (2ꢀAd)
2
5
ring-opening reaction of D-A cyclopropanes. With the Cy-
TOX/Cu(II) as catalyst, the reaction performed very well over
a broad range of substrates, leading to the ring opening
products in excellent yields (up to 96%) with excellent levels
of enantioselectivity (up to 96% ee) under mild conditions.
This method provides a new approach to access directly to γ-
substituted GBH derivatives very efficiently from activated
cyclopropanes. Importantly, the strategy by employing hy-
drate catalyst as a reservoir to controlled-release of water
(
2
Adꢀ2)O C
5
0% yield
1
0 mol% cat., DME
product 4a not observed (3)
"
H O free", 4Å MS
2
1
0 mol%
4
a
L8/Cu(ClO ) •6H
2
O
4
2
71 % yield, 89% ee
(4)
DME
might pave a way for asymmetric H O-nucleophilic reac-
2
tions. Further study on the applications of this methodology
is underway.
x
0
0
y
x
y
x
y
a
34 0.5 78 1.5 35
.1 40 0.6 79 2.0 22
0.2 56 0.8 74 5.0 23
Table 4. Substrate Scope.
2
CO (2ꢀAd)
OH CO (2ꢀAd)
2
0
0
.3 54 1.0 74
.4 61 1.2 47
15 mol% L8/Cu(ClO ) —6H O
4 2 2
CO (2ꢀAd)
2
R
2
CO (2ꢀAd)
DME, rt
R
x = water loading (eq.)
y = yield of 4a (%)
1
4
Figure 1. Relationship of the Yield and Water Load-
ing. Conditions: All reactions were carried out under Ar at-
mosphere at 40 C, 1a (0.20 mmol), Cu(OTf) (0.020 mmol),
L8 (0.024 mmol), [1a] = 0.20 M in DME (1.0 mL), Isolated
o
2
0
yield based on 1a.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 6
Sun, X. L.; Tang, Y. Angew. Chem., Int. Ed. 2007, 46, 3918-3921. (c)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Parsons, A. T.; Johnson, J. S. J. Am. Chem. Soc. 2009, 131, 3122-3123. (d)
Parsons, A. T.; Smith, A. G.; Neel, A. J.; Johnson, J. S. J. Am. Chem.
Soc. 2010, 132, 9688-9692. (e) Benfatti, F.; de Nanteuil, F.; Waser, J.
Chem.-Eur. J. 2012, 18, 4844-4849. (f) Lin, M.; Kang, G. Y.; Guo, Y. A.;
Yu, Z. X. J. Am. Chem. Soc. 2012, 134, 398-405. (g) Xiong, H.; Xu, H.;
Liao, S. H.; Xie, Z. W.; Tang, Y. J. Am. Chem. Soc. 2013, 135, 7851-7854.
(h) Xu, H.; Qu, J. P.; Liao, S. H.; Xiong, H.; Tang, Y. Angew. Chem.,
Int. Ed. 2013, 52, 4004-4007. (i) Zhou, Y. Y.; Li, J.; Ling, L.; Liao, S. H.;
Sun, X. L.; Li, Y. X.; Wang, L. J.; Tang, Y. Angew. Chem., Int. Ed. 2013,
52, 1452-1456. (j) de Nanteuil, F.; Serrano, E.; Perrotta, D.; Waser, J. J.
Am. Chem. Soc. 2014, 136, 6239-6242. (k) Racine, S.; de Nanteuil, F.;
Serrano, E.; Waser, J. Angew. Chem., Int. Ed. 2014, 53, 8484-8487. (l)
Hashimoto, T.; Kawamata, Y.; Maruoka, K. Nat. Chem. 2014, 6, 702-
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
0
5. (m) Xia, Y.; Liu, X. H.; Zheng, H. F.; Lin, L. L.; Feng, X. M., An-
gew. Chem., Int. Ed. 2015, 54, 227-230. (n) Xu, H.; Hu, J.-L.; Wang, L.;
Liao, S.; Tang, Y., J. Am. Chem. Soc. 2015, 137, 8006-8009.
(
3) (a) Lerchner, A.; Carreira, E. M. J. Am. Chem. Soc. 2002, 124,
4826-14827. (b) Carson, C. A.; Kerr, M. A. Angew. Chem., Int. Ed.
2006, 45, 6560-6563. (c) Lerchner, A.; Carreira, E. M. Chem.-Eur. J.
1
2
2
006, 12, 8209-8219. (d) Young, I. S.; Kerr, M. A. J. Am. Chem. Soc.
007, 129, 1465-1469. (e) Leduc, A. B.; Kerr, M. A. Angew. Chem., Int.
Ed. 2008, 47, 7945-7948. (f) Campbell, M. J.; Johnson, J. S. J. Am.
Chem. Soc. 2009, 131, 10370-10371. (g) Carson, C. A.; Kerr, M. A. Org.
Lett. 2009, 11, 777-779. (h) Sanders, S. D.; Ruiz-Olalla, A.; Johnson, J.
S. Chem. Commun. 2009, 5135-5137. (i) Campbell, M. J.; Johnson, J. S.
Synthesis-Stuttgart 2010, 2841-2852. (j) Jung, M. E.; Chang, J. J. Org.
Lett. 2010, 12, 2962-2965. (k) Gharpure, S. J.; Nanda, L. N.; Shukla, M.
K. Eur. J. Org. Chem. 2011, 6632-6635. (l) Zhang, D.; Song, H.; Qin, Y.
Acc. Chem. Res. 2011, 44, 447-457. (m) Tang, P.; Qin, Y. Synthesis-
Stuttgart 2012, 44, 2969-2984. (n) Wang, Z. W. Synlett 2012, 2311-
2327. (o) Grover, H. K.; Emmett, M. R.; Kerr, M. A. Org. Lett. 2013, 15,
4838-4841. (p) Gharpure, S. J.; Nanda, L. N.; Shukla, M. K. Org. Lett.
Conditions: All reactions were carried out under Ar at-
mosphere at rt, 1 (0.20 mmol) Cu(ClO ) ∙6H O (0.030 mmol),
4
2
2
a
L8 (0.036 mmol) in DME (2.0 mL), isolated yield based on 1.
.0 mmol of 1a was used. 5 mol% of L8/Cu(ClO ) ∙6H O.
1] = 0.20 M in DME (1.0 mL). At 40 °C.
0
b
2
[
4 2 2
c
d
ASSOCIATED CONTENT
Experimental procedures, characterizations and analytical
data of products, and spectra of NMR and HPLC. This mate-
rial is available free of charge via the Internet at
http://pubs.acs.org.
2
014, 16, 6424-6427.
4) (a) Tanimori, S.; Niki, T.; He, M. Q.; Nakayama, M. Heterocy-
cles 1994, 38, 1533-1540. (b) Yu, M.; Pagenkopf, B. L. Tetrahedron
003, 59, 2765-2771. (c) Cao, W.; Ding, W.; Chen, Y.; Gao, J. Syn.
(
2
Commun. 2007, 30, 4531-4541. (d) Leduc, A. B.; Lebold, T. P.; Kerr, M.
A. J. Org. Chem. 2009, 74, 8414-8416. (e) Hu, B.; Ren, J.; Wang, Z.
Tetrahedron 2011, 67, 763-768. (f) Novikov, R. A.; Korolev, V. A.;
Timofeev, V. P.; Tomilov, Y. V. Tetrahedron Lett. 2011, 52, 4996-4999.
(5) (a) Zhou, Y. Y.; Wang, L. J.; Li, J.; Sun, X. L.; Tang, Y. J. Am.
Chem. Soc. 2012, 134, 9066-9069. (b) Kang, Q. K.; Wang, L. J.; Zheng,
Z. B.; Li, J. F.; Tang, Y. Chin. J. Chem. 2014, 32, 669-672. (c) Wales, S.
M.; Walker, M. M.; Johnson, J. S. Org. Lett. 2013, 15, 2558-2561.
AUTHOR INFORMATION
Corresponding Author
tangy@mail.sioc.ac.cn
ACKNOWLEDGMENT
We are grateful for the financial support from the National
Natural Science Foundation of China (nos. 21421091, 21432011,
and 21272250); the National Basic Research Program of China
973 Program) (2015CB856600); the Chinese Academy of
Sciences.
(
6) (a) Wistuba, D.; Traeger, O.; Schurig, V. Chirality 1992, 4, 185-
9
2. (b) Tokunaga, M.; Larrow, J. F.; Kakiuchi, F.; Jacobsen, E. N. Sci-
ence 1997, 277, 936-938. (c) Ready, J. M.; Jacobsen, E. N. J. Am. Chem.
Soc. 2001, 123, 2687-2688. (d) Vanderwal, C. D.; Jacobsen, E. N. J. Am.
Chem. Soc. 2004, 126, 14724-14725. (e) Zhu, S.-F.; Chen, C.; Cai, Y.;
Zhou, Q.-L. Angew. Chem., Int. Ed. 2008, 47, 932-934. (f) Zhu, S.-F.;
Cai, Y.; Mao, H.-X.; Xie, J.-H.; Zhou, Q.-L. Nat. Chem. 2010, 2, 546-
(
REFERENCES
5
51. (g) Gartner, M.; Mader, S.; Seehafer, K.; Helmchen, G. J. Am.
(
1) (a) Danishefsky, S. Acc. Chem. Res. 1979, 12, 66-72. (b) Wong,
Chem. Soc. 2011, 133, 2072-2075. (h) Ford, D. D.; Nielsen, L. P.; Zuend,
S. J.; Musgrave, C. B.; Jacobsen, E. N. J. Am. Chem. Soc. 2013, 135,
15595-15608. (i) Li, J.; Liao, Y.; Zhang, Y.; Liu, X.; Lin, L.; Feng, X.
Chem. Commun. 2014, 50, 6672-6674.
H. N. C.; Hon, M. Y.; Tse, C. W.; Yip, Y. C.; Tanko, J.; Hudlicky, T.
Chem. Rev. 1989, 89, 165-198. (c) Reissig, H.-U.; Zimmer, R. Chem.
Rev. 2003, 103, 1151-1196. (d) Yu, M.; Pagenkopf, B. L. Tetrahedron
005, 61, 321-347. (e) Rubin, M.; Rubina, M.; Gevorgyan, V. Chem.
Rev. 2007, 107, 3117-3179. (f) Carson, C. A.; Kerr, M. A. Chem. Soc. Rev.
009, 38, 3051-3060. (g) DeꢁSimone, F.; Waser, J. Synthesis 2009,
3353-3374. (h) Lebold, T. P.; Kerr, M. A. Pure. Appl. Chem. 2010, 82,
1797-1812. (i) Mel’nikov, M. Y.; Budynina, E. M.; Ivanova, O. A.;
Trushkov, I. V. Mendeleev Commun. 2011, 21, 293-301. (j) Cavitt, M.
A.; Phun, L. H.; France, S. Chem. Soc. Rev. 2014, 43, 804-818. (k) de
Nanteuil, F.; De Simone, F.; Frei, R.; Benfatti, F.; Serrano, E.; Waser,
J. Chem. Commun. 2014, 50, 10912-10928. (l) Green, J. R.; Snieckus, V.
Synlett 2014, 25, 2258-2259. (m) Schneider, T. F.; Kaschel, J.; Werz, D.
B. Angew. Chem., Int. Ed. 2014, 53, 5504-5523. (n) Grover, H. K.; Em-
mett, M. R.; Kerr, M. A. Org. Biomol. Chem. 2015, 13, 655-671.
2
(
7) (a) Corey, E. J.; Bakshi, R. K.; Shibata, S.; Chen, C.-P.; Singh, V.
K. J. Am. Chem. Soc. 1987, 109, 7925 - 7926. (b) Corey, E. J.; Link, J. O.
Tetrahedron Lett. 1989, 30, 6275 - 6278. (c) Schiffers; Kagan Synlett
2
1997, 1997, 1175 - 1178. (d) Hilborn, J. W.; Lu, Z.-H.; Jurgens, A. R.;
Fang; Byers, P.; Wald, S. A.; Senanayake, C. H. Tetrahedron Lett.
2001, 42, 8919 - 8921. (e) Lipshutz, B. H.; Lower, A.; Kucejko, R. J.;
Noson, K. Org. Lett. 2006, 8, 2969 - 2972. (f) Matsumura, Y.; Ogura,
K.; Kouchi, Y.; Iwasaki, F.; Onomura, O. Org. Lett. 2006, 8, 3789 -
3
2
792. (g) Takeuchi, T.; Matsuhashi, M.; Nakata, T. Tetrahedron Lett.
008, 49, 6462 - 6465. (h) Broussy, S.; Cheloha, R. W.; Berkowitz, D.
B. Org. Lett. 2009, 11, 305 - 308. (i) Periasamy, M.; Sanjeevakumar, N.;
Dalai, M.; Gurubrahamam, R.; Reddy, P. O. Org. Lett. 2012, 14, 2932 -
(
2) For recent leading reference, see: (a) Sibi, M. P.; Ma, Z. H.; Jas-
2935. (j) Covell, D. J.; White, M. C. Tetrahedron 2013, 69, 7771-7778.
perse, C. P. J. Am. Chem. Soc. 2005, 127, 5764-5765. (b) Kang, Y. B.;
ACS Paragon Plus Environment

Page 5 of 6
Journal of the American Chemical Society
(
8) (a) D. A. Evans, S. J. Miller, T. Lectka, P. von Matt J. Am.
Asymmetry. 2010, 21, 1194–1198. (p) Zhu, J.-B.; Chen, H.; Liao, S.; Li,
Y.-X.; Tang, Y. Org. Chem. Front. 2014, 1, 1035–1039.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Chem. Soc. 1999, 121, 7559-7573. (b) Johnson, J. S.; Evans, D. A. Acc.
Chem. Res. 2000, 33, 325-335. (c) J. Zhou, M.-C. Ye, Z.-Z. Huang, Y.
Tang J. Org. Chem. 2004, 69, 1309 -1320. (d) Zhou, J.; Tang, Y. Org.
Biomol. Chem. 2004, 2, 429–433.
(10) For recent uses of TOX and SaBOX ligands, see: (a) Cao, P.;
Deng, C.; Zhou, Y. Y.; Sun, X. L.; Zheng, J. C., Xie, Z., Tang, Y. Angew.
Chem., Int. Ed. 2010, 49, 4463–4466. (b) Zhou, J. L.; Deng, C.; Wang,
Z.; Sun, X. L.; Zheng, J. C.; Tang , Y. Angew. Chem., Int. Ed. 2011, 50,
7874–7878. (c) Zhou, Y. Y.; Sun, X. L.; Zhu, B. H.; Zheng, J. C. Zhou, J,
L.; Tang, Y. Synlett. 2011, 935–938. (d) Rendina, V. L.; Moebius, D. C.;
Kingsbury, J. S. Org. Lett. 2011, 13, 2004–2007. (e) Castillo, M. R.;
Castillón, S.; Claver, C.; Fraile, J. M.; Gual, A.; Martín, M.; Mayoral, J.
A.; Sola, E. Tetrahedron. 2011, 67, 5402–5408. (f) Sawada, T.; Nakada,
M. Tetrahedron: Asymmetry. 2012, 23, 350–356. (g) Rendina, V. L.;
Kaplan, H. Z.; Kingsbury, J. S. Synthesis. 2012, 686–693. (h) Li, J.; Liao,
S. H.; Xiong, H.; Zhou, Y. Y.; Sun, X. L.; Zhang, Y.; Zhou, X. G.; Tang,
Y. Angew. Chem., Int. Ed. 2012, 51, 8838–8841. (i) Deng, C. Wang, L. J.;
Zhu, J.; Tang, Y. Angew. Chem., Int. Ed. 2012, 51, 11620–11623. (j) Zhou,
J. L.; Wang, L. J.; Xu, H.; Sun, X. L.; Tang, Y. ACS Catal. 2013, 3, 685–
688. (k) Wang, P.; Tao, W. J.; Sun, X. L.; Liao, S.; Tang, Y. J. Am.
Chem. Soc. 2013, 135, 16849–16852. (l) Feng, L. W.; Wang, P.; Wang,
L.; Tang, Y. Sci. Bull. 2015, 60, 210–215. (m) Hu, J.-L.; Wang, L.; Xu, H.;
Xie, Z.; Tang, Y. Org. Lett. 2015, 17, 2680-2683.
(
9) For reviews on sidearm strategy, see: (a) Zhou, J.; Tang, Y.
Chem. Soc. Rev. 2005, 34, 664–676. (b) Gade, L. H.; Bellemin–
Laponnaz, S. Chem. Eur. J. 2008, 14, 4142–4152. (c) Hargaden, G. C.;
Guiry, P. J. Chem. Rev. 2009, 109, 2505–2550. (d) Liao, S.; Sun, X. L.;
Tang Y. Acc. Chem. Res. 2014, 47, 2260−2272. For selected examples,
see: (e) Zhou, J.; Tang, Y. J. Am. Chem. Soc. 2002, 124, 9030–9031. (f)
Ye, M. C.; Zhou, J.; Huang, Z. Z.; Tang, Y. Chem. Commun. 2003,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
554–2555. (g) Huang, Z. Z.; Kang, Y. B.; Zhou, J.; Ye, M. C. Tang, Y.
Org. Lett. 2004, 6, 1677–1679. (h) Rasappan, R.; Hager, M.; Gissibl, A.;
Reiser, O. Org. Lett. 2006, 8, 6099–6102. (i) Seitz, M.; Capacchione,
C.; Bellemin–Laponnaz, S.; Wadepohl, H.; Ward, B. D.; Gade, L. H.
Dalton Trans. 2006, 193–202. (j) Xu, Z. H.; Zhu, S. N.; Sun, X. L.; Tang,
Y.; Dai, L. X. Chem. Commun. 2007, 1960–1962. (k) Foltz, C.; Enders,
M.; Bellemin–Laponnaz, S.; Wadepohl, H.; Gade, L. H. Chem. Eur. J.
007, 13, 5994–6008. (l) Foltz, C.; Stecker, B.; Marconi, G.; Bellemin–
Laponnaz, S.; Wadepohl, H.; Gade, L. H. Chem. Eur. J. 2007, 13, 9912–
923. (m) Schätz, A.; Rasappan, R.; Hager, M.; Gissibl, A.; Reiser, O.
2
9
(11) The absolute configuration of the product 4a was determined
by transforming to lactone, and comparing its optical rotations with
the literature: Gutman A. L.; Zuobi K.; Bravdo T. J. Org. Chem. 55,
1990, 3546-3552.
Chem. Eur. J. 2008, 14, 7259–7265. (n) R. Rasappan, T. Olbrich, O.
Reiser, Adv. Synth. Catal. 2009, 351, 1961–1967. (o) Hager, M.; Witt-
mann, S.; Schätz, A.; Pein, F.; Kreitmeier, P.; Reiser, O. Tetrahedron:
(
12) For details, see Supporting Information.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 6 of 6
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
6
ACS Paragon Plus Environment