Formal [5+3] Cycloaddition of Zwitterionic Allylpalladium Intermediates with Azomethine Imines for Construction of N,O-Containing Eight-Membered Heterocycles

Article abstract of DOI:10.1002/adsc.201701247

A formal [5+3] cycloaddition of zwitterionic allylpalladium intermediates with 1,3-dipoles is developed, providing N,O-containing eight-membered heterocyclic compounds in high yields. Catalytically generated zwitterionic allylpalladium intermediates in situ from vinylethylene carbonates or vinyloxiranes acted as dipolarophile. (Figure presented.).

Full text of DOI:10.1002/adsc.201701247

COMMUNICATIONS
DOI: 10.1002/adsc.201701247
1
2
Very Important Publication
3
4
5
6
7
8
9
Formal [5+3] Cycloaddition of Zwitterionic Allylpalladium
Intermediates with Azomethine Imines for Construction of N,O-
Containing Eight-Membered Heterocycles
Chunhao Yuan,+a Yang Wu,+a Dongqi Wang,b Zhenhua Zhang,a Chang Wang,a
Leijie Zhou,a Cheng Zhang,a Baoan Song,c and Hongchao Guoa, c,*
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
a
Department of Applied Chemistry, China Agricultural University, 2 West Yuanmingyuan Road, Beijing 100193, People’s
Republic of China
Fax: (+86) 10-6273-0784; e-mail: hchguo@cau.edu.cn
Institute of High Energy Physics, Chinese Academy of Science, Beijing 100049, Peopleꢀs Republic of China
Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang
b
c
550025, Peopleꢀs Republic of China
+
Both authors contributed equally to this manuscript
Received: September 27, 2017; Revised: November 2, 2017; Published online: December 11, 2017
Supporting information for this article is available on the WWW under https://doi.org/10.1002/adsc.201701247
with medium-sized rings is still of great significance
and is highly desirable.
Abstract: A formal [5+3] cycloaddition of zwitter-
ionic allylpalladium intermediates with 1,3-dipoles
is developed, providing N,O-containing eight-mem-
The cycloaddition reactions involving palladium
catalysis are powerful tools for the synthesis of
bered heterocyclic compounds in high yields. Cata-
carbocyclic and heterocyclic compounds.[7] Particu-
lytically generated zwitterionic allylpalladium inter-
larly, the cycloaddition reactions via zwitterionic
mediates in situ from vinylethylene carbonates or
allylpalladium intermediates from vinyl-oxiranes and
vinyloxiranes acted as dipolarophile.
vinylethylene carbonates have attracted much atten-
tion and have intensely been studied in the past
Keywords: palladium; cycloaddition; vinylethylene
decade (Scheme 1a).[8] Generally, the reactive dipolar
carbonate; vinyloxirane; azomethine imine
38 Medium-ring heterocyclic compounds are an impor-
39 tant class of compounds. They are building blocks in a
40 wide spectrum of natural and unnatural products.
41 Among them, the N- or O-containing medium-ring
42 heterocycles usually showed interesting biological
43 activities.[1] As a result, the synthesis of such medium-
44 ring heterocycles has attracted much attention from
45 the organic and biological community.[2] In comparison
46 with five- to seven-membered rings, the eight-mem-
47 bered rings are more challenging to be accessed for its
48 entropic disadvantages, conformational constraints,
49 and transannular interactions.[3] In spite of the ob-
50 stacles, several strategies have been reported to
51 construct the medium-ring structures, such as transi-
52 tion-metal catalyzed cyclization,[4] ring-closing meta-
53 thesis,[5] ring expansion,[6] etc. However, the diversity
54 of the existing methods still lags behind considering
55 the high importance of such N,O-containing medium-
56 ring of heterocycles. Therefore, developing highly
57 efficient synthetic methods to build such compounds
Scheme 1. Palladium-catalyzed cycloaddition reactions via
zwitterionic allylpalladium intermediates.
Adv. Synth. Catal. 2018, 360, 652–658
652
ꢁ 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

COMMUNICATIONS
asc.wiley-vch.de
1
2
3
4
5
6
7
8
9
species, which were generated from vinyloxiranes and regioselectivity (entry 9). However, the diphosphine
vinylethylene carbonates through ring-opening or L4 with a more rigid structure showed less efficiency
decarboxylation, acted as three-membered synthons in than L3 (entry 10). Substitution of the diphenyl groups
the [3+2] cycloaddition reactions with diverse sub- in L3 with dicyclohexyl groups showed much worse
strates including carbodiimides,[9] aldehydes,[10] isocya- performance than L3 (entry 11). Subsequently, other
nates,[11] CO2,[12] alkenes,[13] and imines,[14] providing solvents, such as toluene, CHCl3, and 1,2-dichloro-
five-membered cycloadducts with impressive results ethane (DCE) were screened. showed less efficiency
(Scheme 1a). In comparison, the role of the zwitter- than CH2Cl2, while THF were not a suitable solvent
ionic palladium intermediates serving as five-mem- when the product 3aa was not obtained. The structure
10 bered synthons in cycloaddition reactions have never of the product 3aa was unequivocally determined
11 been investigated until most recently, a palladium- through X-ray crystallography.[20]
12 catalyzed [5+4] cycloaddition of N-tosyl azadienes
13 with substituted vinylethylene carbonates to produce
Table 1. Optimization of reaction conditions[a]
14 nine-membered heterocycles was achieved by Zhao.[15]
15
1,3-dipoles are readily accessible reaction partners
16 and have widely been used as three-membered
17 synthons in cycloaddition reactions for the construc-
18 tion of ring structures.[16] In recent years, the impor-
19 tance of cycloaddition reactions of stable dipoles with
20 reactive dipolar intermediate formed in situ has been
21 recognized.[17] This type of stepwise formal cyclo-
22 addition have become a hot topic in the area of
23 cycloaddition reactions. Many types of reactive dipolar
24 intermediates from metal catalysis[18] and organocatal-
25 ysis[19] have been reported being applied to cyclo-
26 addition reactions with stable 1,3-dipoles.[17] However,
27 the zwitterionic allylpalladium intermediates from
28 vinyloxiranes and vinylethylene carbonates have never
29 been investigated in such cycloaddition reactions.
30 Herein we report a formal [5+3] cycloaddition of
31 zwitterionic allylpalladium intermediates as five-mem-
32 bered synthons with 1,3-dipoles for the synthesis of
33 eight-membered N,O-containing heterocycles (Sche-
34 me 1b).
Entry Ligand
Solvent t [h] Yield [%][b] [5+3]/
[3+3][c]
1
PPh3
CH2Cl2 12
76
trace
35
trace
trace
80
90:10
–
95:5
–
2
3
MePh2P CH2Cl2 72
Me2PhP CH2Cl2 72
4
5
6
Bu3P
DPPB
L1
CH2Cl2 72
CH2Cl2 72
CH2Cl2 48
CH2Cl2 72
CH2Cl2 36
–
3:1
10:1
1:3
97:3
98:2
8:2
9:1
98:2
9:1
–
7
dppf
7
61
35
Initially, the reaction of vinylethylene carbonate 2a
8
L2
36 with N-iminoquinazolinium ylides 1a was employed as
37 the model reaction to investigate the optimal reaction
38 conditions (Table 1). To our great delight, in the
39 presence of 2.5 mol% of Pd2(dba)3·CHCl3 and
40 7.5 mol% of Ph3P, the desired [5+3] cycloadduct was
41 obtained as major product in 76% yield with 90:10
42 regioselectivity (entry 1). It seems that substitution of
43 the phenyl groups in PPh3 by any alkyl groups was
44 harmful for the reaction. MePh2P, Bu3P and dppb did
45 not show any activity for the reaction, and Me2PhP
46 offered the product 3aa in 35% yield with 95:5
47 regioselectivity (entries 2–5). The tri-2-furylphosphine
48 (L1) provided high yields of cycloadducts but with low
49 regioselectivity (entry 6). Ferrocenyl phosphines, such
50 as dppf and L2, are active ligands for the reaction
51 (entries 7–8), but the ligand L2 offered the product
52 3aa with worse regioselectivity in comparison with
9
L3
CH2Cl2
3
86
10
11
12
13
14
15
L4
L5
L3
L3
L3
L3
CH2Cl2 12
CH2Cl2 72
toluene 72
70
20
50
CHCl3
DCE
THF
24
24
72
55
70
trace
[a] All reactions were carried out with 1a (0.1 mmol), 2a
(0.15 mmol), Pd2(dba)3 ·CHCl3 (2.5 mol%) and ligand
(7.5 mol%) in 3 mL of solvent at rt under indicated
reaction conditions.
[b] Isolated yield.
[c] Determined by HPLC analysis.
With the optimal reaction conditions in hand, the
53 dppf, probably due to the bulkier substituents in L2 substrate scope of vinylethylene carbonates was fur-
54 (entry 8). As a result, several types of bidentate ther expanded. As shown in the Table 2, for the aryl
55 arylphosphines were further tested for the model substituted vinylethylene carbonates, the correspond-
56 reaction. Excitingly, a flexible diphosphine L3 af- ing products were obtained in moderate to good yields
57 forded the product 3aa in high yield with excellent with good to excellent regioselectivities (entries 1–12).
Adv. Synth. Catal. 2018, 360, 652–658
653
ꢁ 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

COMMUNICATIONS
asc.wiley-vch.de
1
2
3
4
5
6
7
8
9
Notably, the 2-naphthyl substituted substrate was also yield albeit with excellent regioselectivity. Subse-
favourable for the cycloaddition. The corresponding quently, several different sulfonyl groups protected
product 3al was obtained in high yield with excellent ylides were also examined and they provided the
regioselectivity (entry 12). The alkyl-substituted vinyl- desired cycloadducts (3fa–3ja) with high yields as well
ethylene carbonates have also been examined in this as excellent regioselectivities. Among them, the 4-
cycloaddition (entries 13–14). The methyl substituted MeO or 4-Cl substituted benzenesulfonyl protected
vinylethylene carbonate (2m) provided the [5+3] ylides gave relatively lower yields than other sulfonyl
cycloadduct 3am as the minor product with poor protected ylides did. In addition, the 1-naphthylsulfon-
regioselectivity (60:40) in spite of the excellent yield yl protected ylide is also a suitable substrate and the
10 (94%) (entry 13). However, the bulkier t-Bu-substi- desired cycloadduct 3ja was offered in 94% yield with
11 tuted vinylethylene carbonate (2n) underwent the 99:1 regioselectivity. It is worth mentioning that the N-
12 cycloaddition reaction to give the [5+3] cycloadduct isoquinolinium ylides were also applicable substrates
13 3an as the major product with greatly improved for the [5+3] cycloaddition reactions. All of the tested
14 regioselectivity (95:5) albeit with decreased yield 1,3-dipoles afforded the corresponding [5+3] cyclo-
15 (71%) (entry 14).
16
adducts (3ka–3ma) in high yields with excellent
regioselectivities. The cycloadduct 3ka was obtained
with high yield and excellent regioselectivity after 12 h
of reaction. The fluorine-substituent, as well as its
substitution position, did show some influence on the
reaction results: the cycloadducts 3la and 3ma were
obtained with lower yields after longer time of
reaction (24 h) compared with 3ka, and the yield of 6-
F-substituted cycloadduct 3ma was even lower than
that of the 7-F-substituted cycloadduct 3la, however,
the regioselectivities remain excellent.
17
18
Table 2. Substrate scope of the vinylethylene carbonates[a]
19
20
21
22
Entry
R
t [h]
3
Yield [5+3]/
[%][b] [3+3][c]
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
1
2
3
4
5
6
7
8
Ph (2a)
3
6
6
6
24
6
8
10
16
12
12
8
3aa
3ab
3ac
3ad
3ae
3af
3ag
3ah
3ai
3aj
3ak
3al
3am 94
3an 71
86
80
72
72
62
64
61
65
62
71
70
80
97:3
99:1
99:1
97:3
92:8
99:1
96:4
99:1
>99:1
93:7
93:7
>99:1
60:40
95:5
4-MeC6H4 (2b)
3-MeOC6H4 (2c)
4-MeOC6H4 (2d)
2-FC6H4 (2e)
4-FC6H4 (2f)
3-ClC6H4 (2g)
4-ClC6H4 (2h)
3,4-Cl2C6H4 (2i)
3-BrC6H4 (2j)
4-BrC6H4 (2k)
2-naphthyl (2l)
Me (2m)
Table 3. Substrate scope of azomethine imines[a]
9
10
11
12
13
14
3
24
t-Bu (2n)
[a] All reactions were carried out with 1a (0.1 mmol), 2
(0.15 mmol), Pd2(dba)3 ·CHCl3 (2.5 mol%) and L3
(7.5 mol%) in CH2Cl2 (3 mL) at rt.
[b] Isolated yield.
[c] Determined by HPLC analysis.
The substrate scope of azomethine imines includ-
47 ing both N-quinazolinium ylides and N-isoquinolinium
48 ylides, were next explored (Table 3). For the substrates
49 of N-quinazolinium ylides, electron-donating groups
50 on the phenyl ring did not show significant difference
51 on the results, and all the tested ylides afforded the
52 corresponding products (3ba, 3ca and 3da) in high
53 yields with excellent regioselectivities. It seems that
54 the fluoro-substituted N-quiniazolinium ylide was a
55 more challenging substrate compared to the electron-
[a] All reactions were carried out with 1 (0.1 mmol), 2a
(0.15 mmol), Pd2(dba)3 ·CHCl3 (2.5 mol%) and L3
(7.5 mol%) in CH2Cl2 (3 mL) at rt.
[b] Isolated yield.
[c] Determined by HPLC analysis.
Further attempts to extend the scope of azome-
56 rich ones and it required 72 h to complete the thine imines were not successful. Other types of
57 reaction, providing the product 3ea in slightly lower azomethine imines including N,N’-cyclic azomethine
Adv. Synth. Catal. 2018, 360, 652–658
654
ꢁ 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

COMMUNICATIONS
asc.wiley-vch.de
Table 4. Pd-catalyzed [5+3] cycloaddition of azomethine imines with vinyloxiranes[a]
1
2
3
4
5
6
7
8
R1
R2
X
R3
t[h]
3
Yield [%][b]
[5+3]/ [3+3][c]
9
H (1k)
H (1n)
Ph
4-MeC6H4
C
C
Ph (4a)
Ph (4a)
12
48
3ka
3na
85
53
>99:1
>99:1
10
11
12
13
14
15
16
17
18
19
20
F (1o)
C
Ph (4a)
48
3oa
51
>99:1
H (1a)
H (1a)
H
H
N
N
3-MeOC6H4 (4c)
4-FC6H4 (4f)
6
16
3ac
3af
52
60
90:10
99:1
[a] Unless otherwise stated, all reactions were carried out with 1 (0.1 mmol), 4 (0.15 mmol), Pd2(dba)3 ·CHCl3 (2.5 mol%) and
L3 (7.5 mol%) in CH2Cl2 (3 mL) at rt.
[b] Isolated yield.
[c] Determined by HPLC analysis.
21 imines,[19b] C,N-cyclic azomethine imines[19a] derived [3+3] product is 20:80 in the case of vinyloxirane 4o.
22 from pyridines, and quinolines were inert in this In these two cases, although the [3+3] cycloaddition
23 formal [5+3] cycloaddition reaction, giving no cyclo- product was produced as major product, the [5+3]
24 adduct.
cycloadduct was still formed in significant amount.
25
In comparison with vinylethylene carbonates, vi-
26 nyloxiranes are more attractive substrates in terms of
27 atom economy. As a result, we further tested the
28 reactivity of vinyloxiranes in the [5+3] cycloaddition
29 under the optimal reactions (Table 4). To our delight,
30 all of the three aryl-substituted vinyloxiranes were
31 well compatible with the reaction conditions. The
32 reaction of 3-Ph substituted N-isoquinolinium ylides
33 1k and Ph-substituted vinyloxirane 4a provided the
34 [5+3] cycloadduct 3ka with 85% yield and excellent
35 regioselectivity (>99:1). Both 4-MePh and cycloprop-
36 yl substituted N-isoquinolinium ylides (1n and 1o)
37 required longer time to complete the reaction with
38 diminished yield (53% and 51% yield respectively)
39 albeit with excellent regioselectivities (>99:1). For N-
40 iminoquinazolinium ylide 1a, the reaction with 3-
Scheme 2. Pd-catalyzed cycloaddition of zwitterionic palladi-
um intermediates.
Following the exploration of the substrate scope,
41 MeOC6H4 substituted vinyloxirane (4c) afforded the we performed the model reaction on gram-scale.
42 corresponding [5+3] cycloadduct 3ac with moderate Under the optimal reaction conditions, the cyclo-
43 52%yield and good regioselectivity (90:10). With the adduct 3aa was obtained in 74% yield with 97:3
44 use of 4-FC6H4 substituted vinyloxirane (4f) as the regioselectivity (Scheme 3). Further treatment of the
45 substrate, the cycloadduct 3af was obtained in 60% product 3aa with Br2 in CHCl3 at room temperature
46 yield with excellent regioselectivity (99:1).
As shown in Scheme 2, besides aryl and alkyl syn-selectivity of dibromination might be caused by
48 substituted vinylethylene carbonates and vinyloxir- the steric hindrance of R group.
for 12 h led to the derivative 5 in 73% yield.[20] The
47
49 anes, unsubstituted vinylethylene carbonate (2o) and
On the basis of the previous investigation on the
50 vinyloxirane (4o) have also been investigated in the mechanism,[7a,8,21] a plausible mechanism was proposed
51 palladium-catalyzed cycloaddition reactions with azo- (Scheme 4). In the presence of Pd catalyst, either
52 methine imines. The reaction of azomethine imine 1a vinylethylene carbonate 2a or vinyloxirane 4a per-
53 and 2o or 4o worked well under the optimal forms ring-opening to give the zwitterionic allylpalla-
54 conditions to give the [5+3] and [3+3] products in dium intermediate A, which undergoes nucleophillic
55 total 90–91%yields. Interestingly, with vinylethylene addition to the azomethine imine 1a to afford the
56 carbonate 2o as the substrate, the ratio of [5+3] to allylpalladium intermediate B. The subsequent N-
57 [3+3] product is 43:57, while the ratio of [5+3] to alkylation might follow two different pathways, lead-
Adv. Synth. Catal. 2018, 360, 652–658
655
ꢁ 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

COMMUNICATIONS
asc.wiley-vch.de
1
2
3
builds h2 interaction with Pd atom. In the meantime,
Pd atom forms a coordination bond with one of the O
˚
atom of the Ts group (dPd-O =2.31 A).
4
In the [5+3] pathway, this mode is identified to be
5
6
7
8
less probable. According to calculations, Pd atom sits
˚
˚
trans to N atom with dPd-C1 =2.31 A and dC1-N =2.31 A.
During the reaction, the C3 maintains its planar
conformation.
9
The presence of the Ph group on C3 also affects the
stability of the product. According to calculations, the
[3+3] product is about 16.6 kcal/mol less stable than
the [5+3] product. Along the [3+3] pathway, the
formation of the C3-N bond closes a chair-like six-
10
11
12
13
Scheme 3. Synthesis on the gram scale and further trans-
formation.
14 ing to two types of products, [5+3] and [3+3] membered ring. This breaks the sp2 hybridization of
15 cycloadducts. The N-alkylation reaction demonstrates C3, and leaves the unsaturated C=C bond at the
16 the high level of regioselectivity, thus producing the terminus.
17 [5+3] cycloaddition product as the major product. For
With the use of unsubstituted vinyloxirane as the
18 shedding light on the excellent regioselectivity, we substrate 4o bearing no Ph group, the electron-
19 investigate the reaction mechanism by computational deficient region, which includes C1, C2 and C3 atoms
20 methods.
and lacks the steric hindrance in the internal position
on the Pd-p-allyl intermediate, is more active to
interact with the N atom. This to some extent weakens
the conjugation in the area of the three C atoms, and
makes it easier to deform the C3 unit and form
covalent bond with N atom. In contrast, the stronger
interaction between Pd and the C=C bond impairs its
access to the N atom of 1a, leading to higher energy
barrier to the [5+3] ring closure than the [3+3] one.
The [3 +3] cycloadduct was thus formed as the major
product.
Overall, according to calculations, the regioselec-
tivity in the presence of a Ph group on 4a is the
consequence of thermodynamic control, while that in
the absence of a Ph group is the result of kinetic
control.
In summary, we have developed a formal [5+3]
cycloaddition of zwitterionic allylpalladium intermedi-
ates with 1,3-dipoles. Under palladium catalysis, zwit-
terionic allylpalladium intermediates formed in situ
from both vinylethylene carbonates and vinyloxiranes
worked well as five-membered synthons under mild
conditions to afford eight-membered N,O-containing
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
Scheme 4. A plausible mechanism
The computational results (the substrates 4a, 4o heterocycles in high yields with excellent regioselectiv-
44 and 1a, and the ligand L3 were chosen for calculation, ities. This is the first time to achieve the formal [5+3]
45 see details in Supporting information) indicated that cycloaddition reaction of zwitterionic allylpalladium
46 the cleavage of the epoxy CÀO bond leaves an intermediates serving as 1,3-dipolarphiles with 1,3-
47 electron-deficient C3 site, which is stabilized by the dipoles. The reaction on the gram-scale and further
48 neighbouring C=C bond via delocalization of the p transformation of the products indicated that the
49 electrons. The presence of a Ph group on the C3 current [5+3] cycloaddition could be a practical tool
50 enhances its stability with the C3 adopting a planar in the synthesis of eight-membered heterocyclic com-
51 conformation, and the deformation at this site costs pounds.
52 energy. This results in the preference of the [5+3]
53 pathway over the [3+3] one. In view of geometry, in
54 the transition states, the catalyst, Pd/L3, sits at differ-
Experimental Section
Under a nitrogen atmosphere, Pd2(dba)3 ·CHCl3 (2.6 mg,
2.5 mol %) and phosphoramidite ligand L3 (4.0 mg, 7.5 mol
%) were dissolved in 1 mL of CH2Cl2, and stirred at room
55 ent places in the two pathways. In the [3+3] pathway,
56 while C3 attacks the N atom of 1a (dC3-N =2.39 A), the
57 C1 and C2 atoms extend out of the active region, and
˚
Adv. Synth. Catal. 2018, 360, 652–658
656
ꢁ 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

COMMUNICATIONS
asc.wiley-vch.de
temperature for about 1 h. Then, N-iminoquinazolinium
ylides (0.1 mmol) in 2 mL of CH2Cl2 and VECs (0.15 mmol)
were added sequentially. The reaction solution was vigo-
rously stirred at 258C and monitored by TLC. After the
reaction was complete, the mixture was directly purified by
column chromatography on silica gel (petroleum ether/
EtOAc as the eluent) to furnish the corresponding product.
The cycloadduct is stable and can be stored in air at room
temperature for several months without remarkable decom-
position.
P. von Zezschwitz, S. Brase, Acc. Chem. Res. 2005, 38,
1
2
3
4
5
6
7
8
9
413; g) E. Guitian, D. Perez, D. Pena, Top. Organomet.
Chem. 2005, 14, 109; h) L. F. Tietze, H. Ila, H. P. Bell,
Chem. Rev. 2004, 104, 3453.
[8] a) A. Khan, Y. J. Zhang, Synlett 2015, 26, 853; b) J. He,
J. Ling, P. Chiu, Chem. Rev. 2014, 114, 8037; c) E. A.
Ilardi, J. T. Njardarson, J. Org. Chem. 2013, 78, 9533;
d) B. Olofsson, P. Somfai, In Aziridines and Epoxides in
Organic Synthesis; Yudin, A. K. Ed. Wiley-VCH Verlag
GmbH & Co. KGaA: Weinheim, Germany, 2006; p 315.
[9] a) C. Larksarp, H. Alper, J. Org. Chem. 1998, 63, 6229;
b) C. Larksarp, H. Alper, J. Am. Soc. Chem. 1997, 119,
3709.
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
Acknowledgements
This work is supported by the NSFC (No. 21372256 and
21572264), and Chinese Universities Scientific Fund
(2017QC162).
[10] A. Khan, R. Zheng, Y. Kan, J. Ye, J. Xing, Y. J. Zhang,
Angew. Chem. Int. Ed. 2014, 53, 6439.
[11] a) A. Khan, J. Xing, J. Zhao, Y. Kan, W. Zhang, Y. J.
Zhang, Chem. Eur. J. 2015, 21, 120; b) M. Raghunath,
X. Zhang, Tetrahedron Lett. 2005, 46, 8213; c) C.
Larksarp, O. Sellier, H. Alper, J. Org. Chem. 2001, 66,
3502; d) B. M. Trost, A. R. Sudhakar, J. Am. Chem. Soc.
1988, 110, 7933; e) B. M. Trost, A. R. Sudhakar, J. Am.
Chem. Soc. 1987, 109, 3792.
References
[1] a) A. Hussain, S. K. Yousuf, D. Mukherjee, RSC Adv.
2014, 4, 43241; b) X. Ma, D. R. Gang, Nat. Prod. Rep.
2004, 21, 752.
[12] a) M. Davousta, F. Cantagrel, P. Metzner, J.-F. Briꢂre,
Org. Biomol. Chem. 2008, 6, 1981; b) B. M. Trost, E. J.
McEachern, J. Am. Chem. Soc. 1999, 121, 8649; c) B. M.
Trost, S. R. Angle, J. Am. Chem. Soc. 1985, 107, 6123.
[13] a) A. Khan, L. Yang, J. Xu, L. Y. Jin, Y. J. Zhang,
Angew. Chem. Int. Ed. 2014, 53, 11257; b) W.-Q. Wu,
C.-H. Ding, X.-L. Hou, Synlett 2012, 23, 1035; c) J.-G.
Shim, Y. Yamamoto, J. Org. Chem. 1998, 63, 3067.
[14] a) L. Yang, A. Khan, R. F. Zheng, L. Y. Jin, Y. J. Zhang,
Org. Lett. 2015, 17, 6230; b) J.-G. Shim, Y. Yamamoto,
Tetrahedron Lett. 1999, 40, 1053; c) J.-G. Shim, Y.
Yamamoto, Heterocycles 2000, 52, 885; d) M. B. Shagha-
fi, R. E. Grote, E. R. Jarvo, Org. Lett. 2011, 13, 5188.
[15] L.-C. Yang, Z.-Q. Rong, Y.-N. Wang, Z. Y. Tan, M.
Wang, Y. Zhao, Angew. Chem. Int. Ed. 2017, 56, 2927.
[16] For recent reviews, see: a) R. Narayan, M. Potowski, Z.-
J. Jia, A. P. Antonchick, H. Waldmann, Acc. Chem. Res.
2014, 47, 1296; b) T. Hashimoto, K. Maruoka, Chem.
Rev. 2015, 115, 5366.
[2] For selected examples, see: a) B. Zhou, L. Li, X.-Q.
Zhu, J.-Z. Yan, Y.-L. Guo, L.-W. Ye, Angew. Chem. Int.
Ed. 2017, 56, 4015; b) J. Elleraas, J. Ewanicki, T. W.
Johnson, N. W. Sach, M. R. Collins, P. F. Richardson,
Angew. Chem. Int. Ed. 2016, 55, 3590; c) L. Huang, L.-
X. Dai, S.-L. You, J. Am. Chem. Soc. 2016, 138, 5793;
d) J.-J. Feng, T.-Y. Lin, CÀZ. Zhu, H. Wang, HÀH. Wu,
J. Zhang, J. Am. Chem. Soc. 2016, 138, 2178; e) J.-J.
Feng, T.-Y. Lin, H.-H. Wu, J. Zhang, J. Am. Chem. Soc.
2015, 137, 3787; f) J.-J. Feng, T.-Y. Lin, H.-H. Wu, J.
Zhang, Angew. Chem., Int. Ed. 2015, 54, 15854; g) X.
Yin, Y. Zheng, X. Feng, K. Jiang, X.-Z. Wei, N. Gao, Y.-
C. Chen, Angew. Chem. Int. Ed. 2014, 53, 6245; h) J.-J.
Feng, J. Zhang, J. Am. Chem. Soc. 2011, 133, 7304.
[3] J. Clayden, W. J. Moran, P. J. Edwards, S. R. LaPlante,
Angew. Chem. Int. Ed. 2009, 48, 6398.
[4] a) T. J. A. Corrie, L. T. Ball, C. A. Russell, G. C. Lloyd-
Jones, J. Am. Chem. Soc. 2017, 139, 245; b) C. Zhao, X.
Xie, S. Duan, H. Li, R. Fang, X. She, Angew. Chem. Int.
Ed. 2014, 53, 10789; c) T. VoCam-Van, M. U. Luescher,
J. W. Bode, Nat. Chem. 2014, 6, 310; d) D. G. Pintori,
M. F. Greaney, J. Am. Chem. Soc. 2011, 133, 1209.
[5] a) Y. Wang, Z.-X. Yu, Acc. Chem. Res. 2015, 48, 2288;
b) X. Yin, Y. Zheng, X. Feng, K. Jiang, X.-Z. Wei, N.
Gao, Y.-C. Chen, Angew. Chem. Int. Ed. 2014, 53, 6245;
c) S. Monfette, D. E. Fogg, Chem. Rev. 2009, 109, 3783;
d) M. E. Maier, Angew. Chem. Int. Ed. 2000, 39, 2073.
[6] a) J. E. Hall, J. V. Matlock, J. W. Ward, K. V. Gray, J.
Clayden, Angew. Chem. Int. Ed. 2016, 55, 11153; b) W.
Zhao, H. Qian, Z. Li, J. Sun, Angew. Chem. Int. Ed.
2015, 54, 10005.
[17] For a review, see: X. Xu, M. P. Doyle, Acc. Chem. Res.
2014, 47, 1396.
[18] For selected examples, see: a) X. Xu, P. Y. Zavalij, M. P.
Doyle, J. Am. Chem. Soc. 2013, 135, 12439; b) M.-C.
Tong, X. Chen, H.-Y. Tao, C.-J. Wang, Angew. Chem.,
Int. Ed. 2013, 52, 12377; c) H. Guo, H. Liu, F.-L. Zhu,
R. Na, H. Jiang, Y. Wu, L. Zhang, Z. Li, H. Yu, B.
Wang, Y. Xiao, X.-P. Hu, M. Wang, Angew. Chem., Int.
Ed. 2013, 52, 12641; d) Y. Zhou, J. Li, L. Ling, S. Liao,
X. Sun, Y. Li, L. Wang, Y. Tang, Angew. Chem., Int. Ed.
2013, 52, 1452; e) X. Xu, P. Y. Zavalij, M. P. Doyle,
Angew. Chem., Int. Ed. 2013, 52, 12664; f) X. Xu, P. Y.
Zavalij, M. P. Doyle, Angew. Chem., Int. Ed. 2012, 51,
9829; g) X. Wang, X. Xu, P. Y. Zavalij, M. P. Doyle, J.
Am. Chem. Soc. 2011, 133, 16402.
[7] a) B. D. W. Allen, C. P. Lakeland, J. P. A. Harrity, Chem.
Eur. J. 2017, 23, 13830; b) K. Muniz, C. Martinez, J.
Org. Chem. 2013, 78, 2168; c) S. Arai, A. Nishida,
Synlett 2012, 23, 2880; d) L.-N. Guo, X.-H. Duan, Y.-M.
Liang, Acc. Chem. Res. 2011, 44, 111; e) R. C. Larock,
Top. Organomet. Chem. 2005, 14, 147; f) A. de Meijere,
[19] For selected examples, see: a) L. Zhang, H. Liu, G.
Qiao, Z. Hou, Y. Liu, Y. Xiao, H. Guo, J. Am. Chem.
Soc. 2015, 137, 4316; b) R. Na, C. Jing, Q. Xu, H. Jiang,
X. Wu, J. Shi, J. Zhong, M. Wang, D. Benitez, E.
Adv. Synth. Catal. 2018, 360, 652–658
657
ꢁ 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

COMMUNICATIONS
asc.wiley-vch.de
Tkatchouk, W. A. Goddard, III, H. Guo, O. Kwon, J.
Am. Chem. Soc. 2011, 133, 13337.
graphic Data Centre via www.ccdc.cam.ac.uk/data_re-
quest/cif.
1
2
[20] CCDC-1545421, 1566585, and 1566590 for the com-
pounds 3aa, 3ao’ and 5ak contain the supplementary
crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallo-
[21] a) Y. Yamamoto, S. Takada, N. Miyaura, Organometal-
lics 2009, 28, 152; b) W. Guo, L. Martꢃnez-Rodrꢃguez, R.
Kuniyil, E. Martin, E. C. Escudero-Adꢄn, F. Maseras,
A. W. Kleij, J. Am. Chem. Soc. 2016, 138, 11970.
3
4
5
6
7
8
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
Adv. Synth. Catal. 2018, 360, 652–658
658
ꢁ 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim