Enantioselective 1,2-Difunctionalization of Dienes Enabled by Chiral Palladium Complex-Catalyzed Cascade Arylation/Allylic Alkylation Reaction

Article abstract of DOI:10.1021/jacs.5b08734

A Pd-catalyzed highly enantioselective three-component coupling of 1,3-dienes with aryl iodines and sodium dialkyl malonates has been successfully established by using a H₈-BINOL-based phosphoramidite ligand. This reaction proceeded via a Pd-catalyzed cascade arylation and asymmetric allylic alkylation reaction, providing an efficient strategy for the enantioselective 1,2-difunctionalization of 1,3-dienes.

Full text of DOI:10.1021/jacs.5b08734

Subscriber access provided by EPFL | Scientific Information and Libraries
Communication
Enantioselective 1,2-Difunctionalization of Dienes Enabled by Chiral
Palladium Complex-Catalyzed Cascade Arylation/Allylic Alkylation Reaction
Xiang Wu, Hua-Chen Lin, Ming-Li Li, Lu-Lu Li, Zhi-Yong Han, and Liu-Zhu Gong
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.5b08734 • Publication Date (Web): 05 Oct 2015
Downloaded from http://pubs.acs.org on October 5, 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 5
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
Enantioselective 1,2-Difunctionalization of Dienes Enabled by Chiral
Palladium Complex-Catalyzed Cascade Arylation/ Allylic Alkylation
Reaction
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
†
†
†
†
†
†‡
§
§
Xiang Wu , HuaꢀChen Lin , MingꢀLi Li , LuꢀLu Li , ZhiꢀYong Han , and LiuꢀZhu Gong*
† Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, University of Science and Technology
of China, Hefei, 230026, China
‡ Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), China
Supporting Information Placeholder
a good enantiomeric excess, but a rather low yield (Figure 2a).
As a consequence, highly efficient and enantioselective 1,2ꢀ
difunctionlization reactions of 1,3ꢀdienes remain highly challengꢀ
ing and are in great demand. Herein, we will describe a highly
regioselective and stereoselective 1,2ꢀdifunctionalizaton of termiꢀ
nal 1,3ꢀdienes with iodoarenes and stabilized carbon nucleophiles
catalyzed by chiral palladium complexes (Figure 2b).
ABSTRACT: A Pdꢀcatalyzed highly enantioselective threeꢀ
component coupling of 1,3ꢀdienes with aryl iodines and sodium
dialkyl malonates has been successfully established by using a H8ꢀ
BINOLꢀbased phosphoramidite ligand. This reaction proceeded
via a palladiumꢀcatalyzed cascade arylation and asymmetric
allylic alkylation reaction, providing an efficient strategy for the
enantioselective 1,2ꢀdifunctionalization of 1,3ꢀdienes.
Figure 1. Pdꢀcatalyzed Difunctionlization of 1,3ꢀDienes
The difunctionalization of alkenes is able to provide a wide range
of structurally diverse functionalized chemicals, which hold great
importance in organic synthesis, and has hence been considered a
powerful strategy in synthetic organic chemistry.1 1,3ꢀDienes are
easily accessible chemicals2 and basically able to participate in a
wide spectrum of reactions by acting on the carbonꢀcarbon double
bonds. Indeed, last several decades have witnessed that 1,3ꢀdiene
derivatives are versatile reagents to render the invention of a large
number of fundamentally important and synthetically significant
methodologies, as exemplified by stereoselective cycloaddition
reactions and polymerizations, which have shown widespread
applications in the medicinal chemistry and material science.3 It
has been recognized that the 1,3ꢀdienes can undergo nucleopalꢀ
As shown in Figure 2c, the Pd(II) intermediate I, generated from
an oxidative addition reaction of a Pd(0) complex to an aryl iodine
2, undergoes a Heck insertion reaction to give an allylic palladium
intermediate II, which will be able to undergo isomerization to
form a πꢀallyl palladium intermediate III8ꢀ12 and then to particiꢀ
pate in allylic alkylation reaction with a stabilized carbon nucleoꢀ
phile, principally giving rise to either a 1,2ꢀproduct 4 or a 1,4ꢀ
product 5. Alternatively, the intermediate II would experience
sequential events including βꢀhydride elimination, reinsertion
reaction via palladium complex IV and isomerization via palladiꢀ
um species IIꞌ to yield a πꢀallyl palladium intermediate IIIꞌ, as
indicated by Sigman.8p,8q,9 The πꢀallyl palladium species IIIꞌ will
also undergo the allylic alkylation reaction, to basically generate
two regiomers 6 and 7. Apparently, the simultaneous control of
both the regioꢀ and stereoselectivity renders the proposed threeꢀ
component reaction much more challenging than similar reactions
established already.8ꢀ11 Since the chiral ligands principally coordiꢀ
nates to all of the palladium species formed in whole reaction
process, we believe that the use of chiral ligands will be able to
provide solutions to formidable issues associated with selectiviꢀ
ties. However, the requirement for the chiral ligands to allow the
proposed threeꢀcomponent reaction proceeding smoothly is quite
critical: they not only enable the palladium to smoothly undergo
the oxidative addition to aryl iodine and the subsequent insertion
reaction, but also are able to efficiently control the stereoselectiviꢀ
ty of the asymmetric allylic alkylation.
ꢀ
ladation with palladium (II) and one nucleophile (Nu1 ) to generꢀ
ate a πꢀallyl palladium intermediate, which can then be trapped by
ꢀ
another nucleophile (Nu2 ) to afford either 1,2ꢀ or 1,4ꢀproducts,
and releasing Pd(0) that is oxidized into catalytically active Pd(II)
for the next catalytic cycle (eq. 1, Figure 1).4ꢀ7 Palladium(0) comꢀ
plexes have also been identified to afford various 1,2ꢀ
difunctionalization reactions upon undergoing oxidative addition
with a high oxidation state compound and subsequent Heck inserꢀ
tion of a 1,3ꢀdiene to form a πꢀallyl palladium species, which
ultimately reacts with a nucleophile to generate a 1,2ꢀ or 1,4ꢀ
additionꢀlike product (eq. 2, Figure 1).8ꢀ12 However, among these
transformations, highly enantioselective 1,2ꢀdifunctionlization
reactions of 1,3ꢀdienes, in particular, the protocols for the forꢀ
mation of two carbonꢀcarbon bonds, have rarely been reportꢀ
ed.10,11 Very recently, Sigman and coꢀworkers established a Pd(0)ꢀ
catalyzed intermolecular 1,2ꢀdiarylation reaction of 1,3ꢀdienes
with aryldiazonium salts and aryl boronic acids, allowing the
installation of two different aryl groups.12 In the presence of a
chiral bicyclo[2.2.2]octadiene ligand, the reaction was able to give
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 5
1
2
3
4
5
6
7
8
9
The feasibility of the hypothesis was initially explored by
Figure 2. Pdꢀcatalyzed Asymmetric 1,2ꢀDifunctionlization of
1,3ꢀDienes
screening chiral ligands for the threeꢀcomponent reaction of (E)ꢀ
1ꢀphenylbutadiene (1a) with iodobenzene (2a) and sodium dimeꢀ
thyl malonate (3a) (Table 1). The chiral ligands commonly emꢀ
ployed in the asymmetric allylic alkylation, including Trost ligꢀ
ands,13 chiral phosphinooxazolineꢀtype P,N ligands14 and others,
which were reported to deliver excellent levels of enantioselecꢀ
tivity in palladium catalysis,15 were initially evaluated. However,
they were unable to give good results (Table S1, in Supporting
Information). Then, chiral phosphoramidite ligands that perform
well in controlling the stereoselectivity of allylic substitutions16
were examined. In the presence of 10 mol % of BINOLꢀbased
phosphoramidite L1,16 Pd(OAc)2 was indeed able to catalyze the
threeꢀcomponent reaction in THF at 80 ºC and the desired 1,2ꢀ
arylalkylation product 4a was isolated in 77% yield and with exꢀ
cellent regioselectivity, but without enantioselectivity (entry 1).
Finely tuning the structure of BINOLꢀderived phosphoramidites
found that ligands L2ꢀL7 bearing substituents at the 3,3’ꢀpositions
of the binaphthyl backbone and 7ꢀposition of 1,2,3,4ꢀ
tetrahydroquinoline, enabled the reaction to deliver even more
promising levels of asymmetric induction (up to 81 % ee, entries
2ꢀ7). A little higher enantiomeric excess was provided by H8ꢀ
BINOLꢀbased phosphoramidite L8 (83% ee, entry 8). The examiꢀ
nation of solvents found that the reaction performed well in ether
solvents (entries 9ꢀ12) and the highest enantioselectivity of 87%
ee was observed in MTBE (entry 9). The variation of reaction
temperature was unable to significantly alter the stereoselectivity
(entries 13 and 14), but a much diminished yield was given at
lower temperature (entry 13). The palladium source did not show
significant effect on the reaction (Table S2, in Supporting Inforꢀ
mation).
After the optimal reaction conditions were established, the genꢀ
erality of the asymmetric transformation was subsequently examꢀ
ined. A variety of arylbutadienes (1bꢀh) and aryliodides (2bꢀh),
possessing same aryl groups, were firstly examined in the presꢀ
ence of 5 mol % of Pd(OAc)2 and 10 mol % of L8 in MTBE at
80 °C (Figure 3). It is necessary to mention that the structures of 4
and 5 are respectively identical to those of 6 and 7 (Figure 2c) in
these cases, and thus only two different regiomers are generated.
The presence of either electronꢀreleasing or deficient substituent
at the paraꢀposition was nicely tolerated and highly regioselecꢀ
tively generated the target products in high yields and enantioseꢀ
lectivity (4bꢀ4d). Obviously, the substitution pattern had considꢀ
erable effect on both regioꢀ and stereoselectivities (4b, 4e and 4f).
For instance, an excellent enantiomeric excess, but a moderate
regioselection was obtained in the reaction involving 2ꢀ
methylphenylbutadiene and 2ꢀmethyliodobenzene (4f). In contrast,
a little lower ee value, but an excellent regioselection was given to
the case with either metaꢀ or orthoꢀmethylphenyl substrate (4b or
4e). Comparing with the results of the substrate with a methyl
group at the orthoꢀposition (4f), the presence of an electronꢀ
withdrawing group such as chloride at the orthoꢀposition of arꢀ
yldiene and aryliodine led to a high regioꢀ and enantioselectivities,
together with a good yield (4g). Further, the sterically hindered
naphthyl substrates also underwent a smooth threeꢀcomponent
coupling reaction in a satisfactory yield and with high levels of
regioꢀ and enantioselectivities (4h). Moreover, different maloꢀ
nates were also examined, providing excellent yields (4i, 90%
yield and 4j, 88% yield) and high levels of enantioselectivities (4i,
83% ee and 4j, 85% ee).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 1. Optimization of the Reaction Conditionsa
Pd(OAc)2 (5 mol%)
PhI
MeO2C
CO2Me
Ph
MeO2C
CO2Me
2a
L
(10 mol%)
+
+
1a
Ph
Ph
*
*
solvents, 80 °C, 72 h
Ph
Na
Ph
5a
4a
1,2-addition
+
MeO2C
CO2Me
R1
1,4-addition
3a
O2N
R
R = H, R1 = H
L1
L2 R = Ph, R1 = H
R
L3 R = 2,4,6-(iPr)3C6H2, R1 = H
L4 R = 9-anthracenyl, R1 = H
L5 R = 3,5-(CF3)2C6H3, R1 = H
O
P
N
O
O
O
P
N
R = 3,5-(CF3)2C6H3, R1 = CF3
R = 3,5-(CF3)2C6H3, R1 = NO2
L6
R
R
L7
L8 R = 3,5-(CF3)2C6H3,
yield
solvent
ee
(%)c
0
ratio
(4a/5a)d
>15:1
>15:1
>15:1
>15:1
>15:1
>15:1
>15:1
>15:1
>15:1
ꢀ
entry
ligand
(%)b
1
2
THF
THF
77
84
21
74
82
90
73
90
89
trace
5
L1
L2
L3
L4
L5
L6
L7
L8
L8
L8
L8
L8
L8
L8
5
3
THF
11
9
4
THF
5
THF
74
79
81
83
87
ꢀ
6
THF
7
THF
8
THF
9
MTBE
DMF
DCM
MeCN
MTBE
MTBE
10
11
12
13e
14f
74
87
88
87
>15:1
>15:1
>15:1
>15:1
27
38
89
aUnless indicated otherwise, reactions of 1a (0.10 mmol), 2a (0.15
mmol), 3a (0.50 mmol), Pd(OAc)2 (0.005 mmol), and L (0.010
mmol) were carried out in a solvent (2 mL) at 80 ºC for 72 h.
Next, the generality for a number of arylbutadienes 1 and arꢀ
yliodides 2, which contain different aryl substituents, was investiꢀ
gated (Figure 4). Basically, four different regiomers are generated
from the reaction, and hence will bring even more challenges to
the simultaneous control of both the regioꢀ and stereoselectivities.
c
d
bIsolated yields. Determined by HPLC analysis. Determined by
1H NMR analysis. The reaction was carried out at 60 ºC. The
e
f
reaction was carried out at 100 ºC.
ACS Paragon Plus Environment

Page 3 of 5
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
To our delight, the application of the optimal conditions to the
was found in the minor regiomer 6sꢀd2 (Scheme 1). More interestꢀ
ingly, an obvious isotope effect was observed for the regioselecꢀ
tivity. An enhanced regioselectivity (> 15/1 vs 11/1) was obtained
for the d2ꢀorthoꢀmethylphenylbutadiene (1sꢀd2), probably due to
that the βꢀdeuteride elimination and reinsertion reactions proceed
much more slowly than the similar transformations with 1s,17 and
thereby rendering the allylꢀPd intermediate IIIꞌ to be much more
slowly formed than III. These experimental results aggregately
indicated that the βꢀhydride elimination and reinsertion reaction to
form allylꢀPd intermediate IIꞌ indeed occurred, leading to minor
products 6 and 7 (Figure 2c).
threeꢀcomponent reaction of (E)ꢀ1ꢀphenylbutadiene (1a) with
different iodobenzenes 2 was quite successful to give the correꢀ
sponding chiral products 4kꢀ4r in high yields ranging from 74%
to 93% and with excellent levels of enantioselectivity of up to
98% ee. Notably, the regioselectivity to preferentially generate 4
over other regiomers was nicely controlled (4kꢀ4q) while less
regioselective control of 1,2ꢀaddition was observed for 2ꢀ
methyliodobenzene reacting with (E)ꢀ1ꢀphenylbutadiene to afford
4r. However, the regiomeric ratios of 1,2ꢀaddition product to
other regiomers seemingly suffer from the orthoꢀ or metaꢀ
substitution with an electronꢀreleasing group (4p and 4r vs 4q).
Using iodobenzene (2a) as the cross coupling partner, a variety of
arylbutadienes were finally evaluated. Obviously, both the regioꢀ
and enantioselectivities are highly sensitive to the aryl substituꢀ
ents (4sꢀ4u). For example, low regioselectivity was obtained for
the reaction with orthoꢀsubstituted phenylbutadiene, albeit with a
high enantioselectivity (4s), while 2ꢀthiophenyl and 1ꢀnaphthyl
substitutedꢀbutadienes could lead to 1,2ꢀproducts with high regioꢀ
and enantioselection (4t and 4u). The structure and absolute
configuration of product 4m was assigned by Xꢀray analysis (see
Supporting Information).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 4. Scope of Arylbutadienes and Aryliodides Containing
Different Aryl Groupsa-e
MeO2C
Ar1
CO2Me
Ar2
MeO2C
Ar1
CO2Me
Ar2
2
I
*
*
Ar2
Ar1
+
Pd(OAc)2 (5 mol%)
L8 (10 mol%)
4j-u
1
5j-u
+
Ar2
Na
MTBE, 80 C, 72 h
Ar2
Ar1
*
Ar1
*
+
MeO2C
CO2Me
MeO2C
7j-u
CO2Me
MeO2C
CO2Me
6j-u
3a
Figure 3. Scope of Arylbutadienes and Aryliodides Containing
the Same Aryl Groupsa-d
+
ArI
Ar
RO2C
CO2R
Pd(OAc)2 (5 mol%)
L8 (10 mol%)
RO2C
CO2R
Ar
2
1
Ar
*
+
Na
CO2R
*
Ar
MTBE, 80 C, 72 h
Ar
+
5b-i
4b-i
RO2C
3
aReactions of 1 (0.10 mmol), 2 (0.15 mmol), 3a (0.50 mmol),
Pd(OAc)2 (0.005 mmol), and L8 (0.010 mmol) were carried out in
MTBE (2 mL) at 80 ºC for 72 h. bYields are reported as a mixture
of regioisomers of 4, 5, 6 and 7. cThe ee values of major products
4 were determined by HPLC analysis. d Unless stated otherwise,
the ratio (r) represented major products (4)/regiomers (5+6+7),
1
e
and was determined by H NMR analysis. The numbers in the
parentheses are the ee values of regiomers 6, and were determined
by HPLC analysis. fThe ratio of 4r/6r /(5r+7r) is 1.0 : 0.10 : 0.18.
gThe ratio of 4s: 6s: (5s+7s) is 1.0: 0.09: 0.13. hFor the characteriꢀ
zation of the minor regiomer 6s, see Supporting Information.
Scheme 1. Experimental Studies on Isotope Effect
aReactions of 1a (0.10 mmol), 2a (0.15 mmol), 3a (0.50 mmol),
Pd(OAc)2 (0.005 mmol), and L8 (0.010 mmol) were carried out in
2 mL of MTBE at 80 ºC for 72 h. b Yields are reported as a mixꢀ
c
ture of regioisomers of 4 and 5. The ee values were determined
d
by HPLC analysis. The ratio (r) represented 4/5 and was deterꢀ
mined by 1H NMR analysis. eThe number in the parenthesis is the
ee value of regiomer 5f, and was determined by HPLC analysis.
fFor the characterization of the minor regiomer 5f, see Supporting
Information.
As shown in Figure 2c, all of the regiomers are generated from
the nucleophilic substitution of two πꢀallylꢀPd intermediates III
and IIIꞌ. To understand how the πꢀallylꢀPd species are generated,
experimental studies on the isotope effect were conducted by the
reaction of d2ꢀorthoꢀmethylphenylbutadiene (1sꢀd2), iodobenzene
(2a) and sodium dimethyl malonate (3a). A similar isotope labelꢀ
ing experiment was reported by Sigman and identified that no
deuterium migration occurs.8p However, the deuterium migration
In summary, we have established a chiral palladium complexꢀ
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 5
1
2
3
4
5
6
7
8
(6) Liao, L.; Sigman, M. S. J. Am. Chem. Soc. 2010, 132, 10209.
catalyzed asymmetric threeꢀcomponent reaction for the difuncꢀ
tionalization of 1,3ꢀdienes with aryl iodines and sodium dialkyl
malonate, resulting in high yields and excellent levels of regioꢀ
and enantioselectivities. The H8ꢀBINOLꢀbased phosphoramidite
turned out to be the optimal ligand, which not only provides high
catalytic activity, but also is able to efficiently control the regioꢀ
and stereoselectivity. The reaction proceeds via a palladiumꢀ
catalyzed cascade arylation and asymmetric allylic alkylation,
capable of tolerating a broad scope of substrates, including 1,3ꢀ
dienes and iodoaryl compounds. Two different types of πꢀallyl
palladium intermediates, respectively generated from migratory
insertion of the 1,3ꢀdiene to aryl Pd(II) and sequential events,
including Heck insertion, βꢀhydride elimination and reinsertion
reactions, are both involved in the whole reaction process. Notaꢀ
bly, this protocol actually provides an important alternative strateꢀ
gy for the enantioselective difunctionalization of 1,3ꢀdienes, leadꢀ
ing to synthetically useful chiral chemicals that were hardly preꢀ
pared from the classical asymmetric allylic alkylation.
(7) For selected examples, see: (a) Bäckvall, J. E.; Bystroem, S. E.;
Nordberg, R. E. J. Org. Chem. 1984, 49, 4619. (b) Bäckvall, J. E.;
Nystroem, J. E.; Nordberg, R. E. J. Am. Chem. Soc. 1985, 107, 3676.
(c) Bäckvall, J. E.; Andersson, P. G. J. Am. Chem. Soc. 1990, 112,
3683. (d) Bäckvall, J. E.; Andersson, P. G. J. Am. Chem. Soc. 1992,
114, 6374. (e) Andersson, P. G.; Bäckvall, J. E. J. Am. Chem. Soc.
1992, 114, 8696. (f) Castano, A. M.; Bäckvall, J.ꢀE. J. Am. Chem.
Soc. 1995, 117, 560. (g) Banerjee, D.; Junge, K.; Beller, M. Org.
Chem. Front. 2014, 1, 368.
(8) For selected examples, see: (a) Patel, B. A.; Dickerson, J. E.; Heck,
R. F. J. Org. Chem. 1978, 43, 5018. (b) Patel, B. A.; Kao, L. C.; Corꢀ
tese, N. A.; Minkiewicz, J. V.; Heck, R. F. J. Org. Chem. 1979, 44,
918. (c) Stakem, F. G.; Heck, R. F. J. Org. Chem. 1980, 45, 3584. (d)
Fischetti, W.; Mak, K. T.; Rheingold, A. L.; Heck, R. F. J. Org.
Chem. 1983, 48, 948. (e) O’Connor, J. M.; Stallman, B. J.; Clark, W.
G.; Shu, A. Y. L.; Spada, R. E.; Stevenson, T. M.; Dieck, H. A. J. Org.
Chem. 1983, 48, 807. (f) Uno, M.; Takahashi, T.; Takahashi, S. J.
Chem. Soc., Chem. Commun., 1987, 785. (g) Grigg, R.; Sridharan, V.
Tetrahedron Lett. 1989, 30, 1139. (h) Larock, R. C.; Fried, C. A. J.
Am. Chem. Soc. 1990, 112, 5882. (i) Larock, R. C.; BerriosꢀPena, N.
G.; Narayanan, K. J. Org. Chem. 1990, 55, 3447. (j) Larock, R. C.;
BerriosꢀPena, N. G.; Fried, C. A.; Yum, E. K.; Tu, C.; Leong, W. J.
Org. Chem. 1993, 58, 4509. (k) Kagechika, K.; Ohshima T.; Shibaꢀ
saki. M. Tetrahedron 1993, 49, 1773. (l) Ohshima, T.; Kagechika, K.;
Adachi, A.; Sodeoka, M.; Shibasaki. M. J. Am. Chem. Soc. 1996, 118,
7108. (m) Deagostino, A.; Prandi, C.; Venturello, P. Org. Lett. 2003,
5, 3815. (n) Yoshida, M.; Sugimoto, K.; Ihara, M. Org. Lett. 2004, 6,
1979. (o) Yeh, M.ꢀC. P.; Tsao, W.ꢀC.; Tu, L.ꢀH. Organometallics
2005, 24, 5909. (p) Liao, L.; Jana, R.; Urkalan, K. B.; Sigman, M. S.
J. Am. Chem. Soc. 2011, 133, 5784. (q) McCammant, M. S.; Liao, L.;
Sigman, M. S. J. Am. Chem. Soc. 2013, 135, 4167.
(9) Saini, V.; O’Dair, M.; Sigman, M. S. J. Am. Chem. Soc. 2015, 137,
608.
(10) Zhu, Y.; Cornwall, R. G.; Du, H.; Zhao, B.; Shi, Y. Acc. Chem. Res.
2014, 47, 3665.
(11) (a) Han, J. W.; Hayashi, T. Tetrahedron: Asymmetry 2010, 21, 2193.
(b) Flubacher, D.; Helmchen, G. Tetrahedron Lett. 1999, 40, 3867.
(12) Stokes, B. J.; Liao, L.; de Andrade, A. M.; Wang, Q.; Sigman, M. S.
Org. Lett. 2014, 16, 4666.
(13) (a) Trost, B. M.; Van Vranken, D. L. Angew. Chem., Int. Ed. Eng.
1992, 31, 228. (b) Trost, B. M.; Van Vranken, D. L.; Bingel, C. J. Am.
Chem. Soc. 1992, 114, 9327. (c) Trost, B. M. Acc. Chem. Res. 1996,
29, 355.
(14) (a) von Matt, P. J.; Helmchen, G. Tetrahedron Lett. 1993, 34, 1769.
(b) Allen, J. V.; Coote, S. J.; Dawson, G. J.; Frost, C. G.; Martin, C. J.;
Williams, J. M. J. J. Chem. Soc., Perkin Trans. 1, 1994, 15, 2065. (c)
Helmchen, G.; Pfaltz, A. Acc. Chem. Res. 2000, 33, 336. (d) Wilꢀ
liams, J. M. J. Synlett 1996, 705.
(15) For reviews, see: (a) Trost, B. M.; Van Vranken, D. L. Chem. Rev.
1996, 96, 395. (b) Trost, B. M.; Crawley, M. L. Chem. Rev. 2003,
103, 2921. (c) Lu, Z.; Ma, S.ꢀM. Angew. Chem., Int. Ed. 2008, 47,
258.
(16) (a) Teichert, J. F.; Feringa, B. L. Angew. Chem. Int. Ed. 2010, 49,
2486. (b) Zhuo, C.ꢀX.; Zheng, C.; You, S.ꢀL. Acc. Chem. Res. 2014,
47, 2558.
(17) (a) Ozawa, F.; Yamamoto, A. J. Am. Chem. Soc. 1980, 102, 6457. (b)
GómezꢀGallego, M.; Sierra, M. A. Chem. Rev. 2011, 111, 4857.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI:
Xꢀray data of 4m (CIF)
Experimental procedures; compound characterization data (PDF)
AUTHOR INFORMATION
Corresponding Author
gonglz@ustc.edu.cn
Author Contributions
§The authors contribute equally to this work.
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
We are grateful for financial support from NSFC (21232007 and
21302177).
REFERENCES
(1) (a) Sigman, M. S.; Werner, E. W. Acc. Chem. Res. 2011, 45, 874. (b)
Jensen, K. H.; Sigman, M. S. Org. Biomol. Chem. 2008, 6, 4083. (c)
McDonald, R. I.; Liu, G.; Stahl, S. S. Chem. Rev. 2011, 111, 2981. (d)
Schultz, D. M.; Wolfe, J. P. Synthesis 2012, 3, 351.
(2) For a recent review on diene synthesis, see: De Paolis, M.; Chataignꢀ
er, I.; Maddaluno, J. Top. Curr. Chem. 2012, 327, 87.
(3) For selected reviews, see: (a) Emily G. Mackay Michael S. Sherburn,
Synthesis 2015, 47, 1. (b) EschenbrennerꢀLux, V.; Kumar, K.; Waldꢀ
mann, H. Angew. Chem., Int. Ed. 2014, 53, 11146. (c) Porri, L.;
Giarrusso, A. In Comprehensive Polymer Science; Pergamon Press:
Oxford, UK, 1989; Vol. 4, p 53. (d) Taube, R.; Sylvester, G. In Apꢀ
plied Homogeneous Catalysis with Organometallic Compounds;
WileyꢀVCH: Weinheim, 1996; Vol. 1, p 280.
(4) Bäckvall, J. E. In MetalꢀCatalyzed CrossꢀCoupling Reactions and
More; De Meijere, Armin; Bräse, Stefan; Oestreich, Martin, Eds.;
WileyꢀVCH: Weinheim, 2014; p 875.
(5) (a) Bar, G. L. J.; LloydꢀJones, G. C.; BookerꢀMilburn, K. I. J. Am.
Chem. Soc. 2005, 127, 7308. (b) Houlden, C. E.; Bailey, C. D.; Ford,
J. G.; Gagné, M. R.; LloydꢀJones, G. C.; BookerꢀMilburn, K. I. J. Am.
Chem. Soc. 2008, 130, 10066. (c) Coscia, R. W.; Lambert, T. H. J.
Am. Chem. Soc. 2009, 131, 2496. (d) Widenhoefer, R. A. Angew.
Chem., Int. Ed. 2009, 48, 6950. (e) Xing, D.; Yang, D. Org. Lett.
2013, 15, 4370.
ACS Paragon Plus Environment

Page 5 of 5
Journal of the American Chemical Society
1
2
3
Table of Content
4
5
6
O2N
Ar
RO2C
Ar1
CO2R
Ar2
Pd(OAc)2 (5 mol%)
L* (10 mol%)
7
8
9
Ar1
+
O
P
N
Ar2-I
+
O
MTBE, 80 oC, 72 h
NaCH(CO2R)2
up to 93% yield, r > 15/1, 98% ee
Ar
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
L*, Ar = 3,5-(CF3)2C6H3
ACS Paragon Plus Environment