Borylation of Olefin C-H Bond via Aryl to Vinyl Palladium 1,4-Migration

Article abstract of DOI:10.1021/jacs.5b11990

The aryl to vinyl palladium 1,4-migration was realized for the first time. The generated alkenyl palladium species was trapped by diboron reagents under Miyaura borylation conditions, providing a new method to synthesize β,β-disubstituted vinylboronates. The excellent regioselectivity and broad substrate scope were observed for this novel transformation.

Full text of DOI:10.1021/jacs.5b11990

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Communication
Borylation of Olefin C-H Bond via Aryl to Vinyl Palladium 1,4-Migration
Tian-Jiao Hu, Ge Zhang, Ya-Heng Chen, Chen-guo Feng, and Guo-Qiang Lin
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.5b11990 • Publication Date (Web): 22 Feb 2016
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Borylation of Olefin C-H Bond via Aryl to Vinyl Palladium 1,4-Migration
TianꢀJiao Hu, Ge Zhang, YaꢀHeng Chen, ChenꢀGuo Feng,* GuoꢀQiang Lin
CAS Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, Shanghai 200032, P. R. China
RECEIVED DATE (automatically inserted by publisher); fengcg@sioc.ac.cn
some results that indicated that palladium tends to migrate to a
Abstract: The aryl to vinyl palladium 1,4ꢀmigration was
realized for the first time. The generated alkenyl palladium
species was trapped by diboron reagents under Miyaura
borylation conditions, providing a new method to synthesize
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more acidic position.16 Thus, the vinyl moiety in relating research
was usually used as a relay station via Heck addition to generate a
sequent palladium migration and no direct functionalization of a
vinyl C-H bond has been reported. 11
β,
βꢀdisubstituted
vinylboronates.
The
excellent
regioselectivity and broad substrate scope were observed
for this novel transformation.
We speculate that if the migration from Larock’s arylpalladium
II
to
the alkenylpalladium I did exist,17 the resulting
intermediate I could be trapped by coupling with other reagents,
such as arylboronic acid, olefin or diboron reagents, and lead to a
new palladium migration/functionalization process (Scheme 1b).
Following this hypothesis, we tested aryl bromide 1a under
Suzuki, Heck or Miyaura reaction conditions. To our delight, the
desired 1, 4-migration product 2a was obtained in 37% yield
under the Miyaura borylation reaction conditions (eq 1).18,19
In search of more efficient and green organic transformations,
the metal-catalyzed direct functionalization of C-H bonds has
been playing an increasingly important role in nearly all areas of
chemical science.1 In order to activate a specific inert C-H bond,
the intramolecular directing strategy is frequently applied through
the introduction of a chelating2 or preoxidized (such as halides)3
functional group at the neighboring position. The latter approach
is often accompanied by a metal migration from the original
position to a remote destination, which proved to be quite
common for various used metals such as Pd,4 Rh,4,5 Ir,6 Co7 etc.
Pd(PPh3)4 (5 mol %)
+
(1)
B(pin)
B2(Pin)2, KOAc,
dioxane, 110 o
Br
B(pin)
3a, 5%
C
1a
2a, 37%
Inspired by this preliminary result, extensive screening of the
reaction conditions were carried out to further promote this
palladium migration/borylation reaction and some representative
results were outlined in Table 1. As a frequently used solvent in
many palladium migration reactions, DMF significantly improved
the regioselectivity (2a/3a = 12:1), albeit with 27% reaction yield
(entry 1). If the solvent was switched to toluene, DCM or dioxane,
the reaction yields were slightly improved, however the
regioselectivities were compromised (entries 2-4). THF proved to
be the best choice giving the highest yield and regioselectivity
(67% yield of 2a; 2a/3a = 14:1; entry 5). High regioselectivities
were observed with acetate and pivalate salts as bases. While the
use of K2CO3 and PhOK decrease the ratio of 2a and 3a to 1:1
(entries
8
and 9), CsF and K3PO4 showed reverse
regioselectivities (entries 10 and 11). The effectiveness of acetate
and pivalate compared with other base suggested the C-H
Scheme 1. C-H Functionalization via Palladium Migration
activation step might occur via
a concerted metalation
deprotonation (CMD) process, where they played as internal bases
for proton abstraction.20 The ligand effect was also examined.
While electron-rich mono-phosphine ligands provided higher
reaction yields of 2a, electron-deficient ones reduced both the
reaction yield and regioselectivity (entries 13-16). Sterically
hindered mono-phosphine L6 significantly improved the
regioselectivity to an excellent level (2a/3a > 20:1) but with a
reduced reactivity (entry 18). This trend was also in accordance
with the results with bis-phosphine ligands dppe and dppp, with
which moderate reaction yields and excellent regioselectivities
were obtained (entries 20 and 21). This dependence of the
regioselectivity on the steric hindrance of ligands hints that the
As a result, the palladium migration have been extensively
studied,8 and a variety of migration types including aryl to aryl,9
vinyl to aryl,10 alkyl to aryl,11 benzylic to aryl, 12 aryl to alkyl13
and aryl to benzylic14 migrations have been reported.15 Although
the seminal work by Larock demonstrated the vinyl to aryl
palladium 1,4-migration as a reversible process in the mechanistic
diagram (Scheme 1b),10a no experimental evidence was provided
to support this feasibility. Some subsequent experiments even
hinted that the reverse process might not be possible.15a One
possible challenge for the palladium migration to a vinyl position
may attribute to the relatively weak acidity of the vinyl C-H bond,
which has a strong influence on the migration trend supported by
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driving force of this palladium migration may be attributed to the
obtained for all the tested substrates. The substituent effect on the
1
2
3
4
5
6
7
8
less steric encumbrance of the vinyl position compared with the
original aryl position. With the most active tris(4-
methoxyphenyl)phosphine L4 as ligand, further screening of
reaction conditions revealed the remarkable effect of TBAB for
the regioselectivity (entry 22). The reaction yield was further
improved to 89% when it was run in a slightly diluted
concentration (entry 23).
phenyl ring A was first examined. The reaction works efficiently
on the substrates containing electron-donating groups (such as Me
(2b) or MeO (2c) ) or electron-withdrawing groups (such as F
(2d), Cl (2e) or CF3 group (2f)) on the para-position of the phenyl
ring A. Compared with the substitution on the para position, the
shift of methyl group to meta- or ortho-positon gave reduced
reaction yields (2g and 2h). Notably, alkenes with the phenyl ring
A replaced by a naphthyl, 2-thienyl or 3-pyridinyl group were
competent substrates for this reaction (2i-2k). The reaction with
substrates bearing different substituents on the phenyl ring B also
proceeded smoothly to afford the borylated products in good
reaction yields (2l-2q). In addition, the structure of 2b was
verified by X-ray crystallographic analysis.
Table 1. Reaction Conditions Optimizationa
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Table 2. Synthesis of β, β-Diarylated Vinylboronatesa,b,c
yield of
2a/3a
entry
1
Solvent
DMF
toluene
DCM
dioxane
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
base
Ligand
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
L1
2a (%)b
ratioc
KOAc
KOAc
KOAc
KOAc
KOAc
CsOAc
CsOPiv
K2CO3
PhOK
CsF
27
41
12:1
3:1
2
3
28
4:1
4
38
5:1
5
67
14:1
11:1
8:1
6
70
7
73
8
10
1:1
9
26
1:1
10
11
12
13
14
15
16
17
18
19d
20d
21d
22e
23e,f
13
1:3
K3PO4
TEA
4
1:10
-
trace
77
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
10:1
6:1
L2
58
L3
37
8:1
L4
85
10:1
10:1
>20:1
-
L5
73
L6
48
dppm
dppe
dppp
L4
nd
67
>20:1
>20:1
>20:1
>20:1
a Reactions conditions: 1 (0.3 mmol), B2(pin)2 (0.345 mmol), Pd(OAc)2
(0.015 mmol), L4 (0.0225 mmol), TBAB (0.03mmol) and CsOAc (0.6
mmol) in THF (12 mL) at 110 oC for 3 h unless otherwise noted. b Isolated
75
85
89 (80)g
c
yields. The possible E/Z isomers were estimated to be less than 1%
L4
compared with the desired products (see support information for details).
a
Reactions conditions: 1a (0.3 mmol), B2(pin)2 (0.345 mmol), Pd(OAc)2
Encouraged by the above result, we tried to test the replacement
of the aromatic ring A by other substituents (Table 3). The
reaction with substrates bearing alkyl substituents took place
smoothly, affording the desired products in good yields (entries 1-
3). CO2Me and CN groups were also tolerated, albeit in reduced
reaction yields (entries 4 and 5).
To gain some mechanistic insight into the present
transformation, several deuterium labeling experiments were
conducted. An intermolecular competition between arylbromide
1u and its dideuterated analogue d2-1u showed a kinetic isotope
effect kH/kD = 2.4 (Scheme 2a), suggesting the C-H bond cleavage
is involved in the rate-determining step. In palladium migration
(0.015 mmol), ligand (0.0225 mmol) and base (0.6 mmol) in solvent (6
o
1
mL) at 110 C for 3 h unless otherwise noted. b Determined by H NMR
spectroscopy using CH2Br2 as an internal standard. Determined by 1H
c
NMR. d The reaction time was prolonged to 4 h. e TBAB (0.03mmol) was
added. f 12 ml THF was used. Isolated yield, which was about 10%
g
lower than 1H NMR yield due to the product instability on silica gel.
TBAB = tetra-n-butylammonium bromide; nd = not dectected.
With optimal reaction conditions in hand, the scope of the
palladium-catalyzed 1,4-migration/borylation reaction for the
synthesis of β, β-diarylated vinylboronates was explored (Table
2).21 Excellent regioselectivities and good reaction yields were
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reactions, a simultaneous migration of hydrogen in the opposite
small amount of acetate. These results clearly demonstrated the
key effect of the acetate for the palladium migration, most
possibly on the C-H activation step.
1
2
3
4
5
6
7
8
direction usually will be accompanied. We tested the dideuterated
arylbromide d2-1u under reaction conditions, and found 30%
incorporation of deuterium into the ortho-position of phenyl ring
(Scheme 2b). The loss of deuterium could be explained by the H-
D exchange between palladium migration intermediates and the
reaction media, which was supported by the high deuterium
incorporation ratio when arylbromide 1u was subjected to this
reaction in the presence of 4 equiv of D2O (Scheme 2c).
Figure 1. Plausible Palladium Migration Mechanism
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Table 3. Synthesis of Other β, β-Disubstituted Vinylboronatesa
Based on the above experimental observations, a proposal on
the palladium migration mechanism is outlined in Figure 1.
Oxidative addition of arylbromide to palladium(0) generates the
intermediate 4. Instead of a second oxidative addition to form
palladium(IV) species, theoretical studies have revealed that a
CMD mechanism would be energetically favored for the next C-H
activation step.20 Although the effectiveness of carboxylates
supports an intramolecular base-assisted proton abstraction, an
intermolecular mode can’t be ruled out with the awareness of the
success of bis-phosphine ligands.20c The generated five-membered
palladacycle 5 was protonated to render a net 1,4-palladium shift
from the aryl to vinyl position, and then proceeds through the
following Miyaura borlyation sequences to afford the
vinylboronate 2a.22
In summary, the first aryl to vinyl palladium 1, 4-migration was
realized by a rationally designed experiment. The resulting
alkenyl palladium intermediate was trapped by diboron reagents
under Miyaura borylation conditions, providing a new method to
synthesize β, β-disubstituted vinylboronates.23 The excellent
regioselectivity and broad substrate scope were observed for this
reaction. The key C-H activation step was believed to proceed via
a CMD mechanism, which was implied by the effectiveness of
acetate or pivalate salts in this reaction, and was in consist with
the preliminary deuterium labeling experiments. Further studies to
elucidate the mechanism of this reaction, and investigations into
the application of this palladium migration mode are underway.
entry
R
Me
product
2r
yield (%)b
1
2
3
4
5
57
66
71
40
33c
Et
2s
n-Pr
CO2Et
CN
2t
2u
2v
a Reactions conditions: 1 (0.3 mmol), B2(pin)2 (0.345 mmol), Pd(OAc)2
(0.015 mmol), L4 (0.0225 mmol), TBAB (0.03mmol) and CsOAc (0.6
mmol) in THF (12 mL) at 110 oC for 3 h. b Isolated yields unless otherwise
noted. c Determined by 1H NMR spectroscopy.
Acknowledgement. We gratefully acknowledge the 973
Program (2015CB856600), the National Natural Science
Foundation of China (21472212), the Shanghai Municipal
Committee of Science and Technology (14ZR1448500) and the
Collaborative Innovation Center of Chemical Science and
Engineering (Tianjing) for financial support.
Scheme 2. Deuterium labeling experiments
Pd(PPh3)4 (5 mol %)
+
B(pin)
B2(pin)2, CsF
THF, 110 o
Supporting Information Available: Experimental procedures
and spectral data for all new compounds (PDF). Crystallographic
data in CIF format for product 2b. This material is available free
of charge via the Internet at http://pubs.acs.org.
References
Br
B(pin)
3a
86%
46%
40%
C
1a
2a
nd
19%
without KOAc:
adding 0.2 equiv KOAc:
Pd(OAc)2/PPh3 instead of Pd(PPh3)4:
( result from Table 1, entry 10)
13%
Scheme 3. The effect of acetate for the migration product
(1) For general reviews on transition metal-catalyzed C–H activation: (a)
Shilov, A. E.; Shul'pin, G. B. Chem. Rev. 1997, 97, 2879. (b) Jia, C..;
Kitamura, T.; Fujiwara, Y. Acc. Chem. Res. 2001, 34, 633. (c) Ritleng, V.;
Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102, 1731. (d) Kakiuchi, F.;
Chatani, N. Adv. Synth. Catal. 2003, 345, 1077. (e) Bergman, R. G. Nature
2007, 446, 391. (f) Li, B.- J.; Yang, S.- D.; Shi, Z. -J. Synlett 2008, 949.
(g) Chen, X.; Engle, K. M.; Wang, D. -H.; Yu, J. -Q. Angew. Chem. Int.
Ed. 2009, 48, 5094. (h) Bouffard, J.; Itami, K. Top. Curr. Chem. 2010, 292,
231. (i) Arockiam, P. B.; Bruneau, C.; Dixneuf, P. H. Chem. Rev. 2012,
112, 5879. (j) Topczewski, J. J.; Sanford, M. S. Chem. Sci. 2015, 6, 70.
(2) For reviews on ligand directed C-H activation: (a) Yu, J. -Q.; Giri, R.;
Chen, X. Org.Biomol.Chem. 2006, 4, 4041. (b) Colby, D. A.; Bergman, R.
G.; Ellman, J. A. Chem. Rev. 2010, 110, 624. (c) Lyons, T. W.; Sanford,
Furthermore, due to the well-known facilitation effect of
acetate on both C-H activation and the Miyaura borylation step,
an experiment to further probe the role of the acetate for this
palladium migration reaction was also performed (Scheme 3).
Using CsF as a base, the borylation smoothly took place in the
original place while the migration product was totally suppressed,
a sharp contrast to the result with Pd(OAc)2/PPh3 as catalyst,
where migration product could be generated in 13% yield. As
anticipated, the ability of migration was recovered by adding a
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M. S. Chem. Rev. 2010, 110, 1147. (d) Ackermann, L. Chem. Rev. 2011,
Rochette, E.; Fontaine, F. G. Science 2015, 349, 513. (l) Saito, Y.; Segawa,
111, 1315. (e) Engle, K. M.; Mei, T. -S.; Wasa, M.; Yu, J. -Q. Acc. Chem.
Res. 2012, 45, 788.
Y.; Itami, K. J. Am. Chem. Soc. 2015, 137, 5193. (m) Wang, G.; Xu, L.; Li,
P. J. Am. Chem. Soc. 2015, 137, 8058.
1
2
3
4
5
6
7
8
(3) For selected leading examples: (a) Ames, D. E.; Bull, D. Tetrahedron
1982, 38, 383. (b) (b) Harayama, T.; Akiyama, T.; Nakano, Y. Chem.
Pharm.l Bull. 1997, 45, 1723. (c) Hennings, D. D.; Iwasa, S.; Rawal, V. H.
J. Org. Chem. 1997, 62, 2. (d) Campeau, L. -C.; Parisien, M.; Leblanc, M.;
Fagnou, K. J. Am. Chem. Soc. 2004, 126, 9186. (e) Campeau, L. -C.;
Thansandote, P.; Fagnou, K. Org. Lett. 2005, 7, 1857.
(20) (a) Davies, D. L.; Donald, S. M. A.; Macgregor, S. A. J. Am. Chem. Soc.
2005, 127, 13754. (b) Garcia-Cuadrado, D.; Braga, A. A. C.; Maseras, F.;
Echavarren, A. M. J. Am. Chem. Soc. 2006, 128, 1066. (c) Pascual, S.; de
Mendoza, P.; Braga, A. A. C.; Maseras, F.; Echavarren, A. M.
Tetrahedron 2008, 64, 6021; (d) Gorelsky, S. I.; Lapointe, D.; Fagnou, K.
J. Am. Chem. Soc. 2008, 130, 10848. (e) Ackermann, L. Chem. Rev. 2011,
111, 1315.; (f) Cheng, G. -J.; Yang, Y. -F.; Liu, P.; Chen, P.; Sun, T. -Y.;
Li, G.; Zhang, X.; Houk, K. N.; Yu, J. -Q.; Wu, Y. -D. J. Am. Chem. Soc.
2014, 136, 894.
(21) For selected examples on the synthesis of multi-substituted vinylboronates:
(a) Negishi, E.; Boardman, L. D. Tetrahedron Lett. 1982, 23, 3327. (b)
Satoh, Y.; Serizawa, H.; Miyaura, N.; Hara, S.; Suzuki, A. Tetrahedron
Lett. 1988, 29, 1811; (c) Coapes, R. B.; Souza, F. E. S.; Thomas, R. L.;
Hall, J. J.; Marder, T. B. Chem. Commun. 2003, 614. (d) Itami, K.;
Tonogaki, K.; Ohashi, Y.; Yoshida, J. Org. Lett. 2004, 6, 4093; (e) Daini,
M.; Yamamoto, A.; Suginome, M. J. Am. Chem. Soc. 2008, 130, 2918; (f)
Wang, C.; Xu, Z.; Tobrman, T.; Negishi, E. Adv. Synth. Catal. 2010, 352,
627; (g)Alfaro, R.; Parra, A.; Alemán, J.; Ruano, J. L. G.; Tortosa, M. J.
Am. Chem. Soc. 2012, 134, 15165; (h) Yoshida, H.; Kageyuki, I.; Takaki,
K. Org. Lett. 2013, 15, 952.
(4) For reviews: (a) Ma, S..; Gu, Z.. Angew. Chem. Int. Ed. 2005, 44, 7512.
(b) Shi, F.; Larock, R. C. Top. Curr. Chem. 2010, 292, 123. .
(5) For selected leading examples: (a) Oguma, K.; Miura, M.; Satoh, T.;
Nomura, M. J. Am. Chem. Soc. 2000, 122, 10464. (b) Hayashi, T.; Inoue,
K.; Taniguchi, N.; Ogasawara, M. J. Am. Chem. Soc. 2001, 123, 9918. (c)
Oguma, K.; Miura, M.; Satoh, T.; Nomura, M. J. Organomet. Chem. 2002,
648, 297. (d) Miura, T.; Sasaki, T.; Nakazawa, H.; Murakami, M. J. Am.
Chem. Soc. 2005, 127, 1390.
(6) Partridge, B. M.; Gonzalez, J. S.; Lam, H. W. Angew. Chem. Int. Ed. 2014,
53, 6523.
(7) Tan, B.-H.; Dong, J.; Yoshikai, N. Angew. Chem. Int. Ed. 2012, 51,
9610.
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
(8) For leading examples: (a) Dyker, G. Angew. Chem. Int. Ed. 1992, 31,
1023. (b) Tian, Q.; Larock, R. C. Org. Lett. 2000, 2, 3329. (c) Wang, L. ;
Pan, Y.; Jiang, X.; Hu, H. Tetrahedron Lett. 2000, 41, 725.
(22) Ishiyama, T.; Murata, M.; Miyaura, N. J. Org. Chem. 1995, 60, 7508.
(23) The Suzuki coupling of iodobenzene with a resulting vinylboronate
(9) For selected examples: (a) Campo, M. A.; Larock, R. C. J. Am. Chem.
Soc. 2002, 124, 14326. (b) Karig, G.; Moon, M. -T.; Thasana, N.;
Gallagher, T. Org. Lett. 2002, 4, 3115. (c) Campo, M. A.; Huang, Q.;
Yao, T.; Tian, Q.; Larock, R. C. J. Am. Chem. Soc. 2003, 125, 11506. (d)
Singh, A.; Sharp, P. R. J. Am. Chem. Soc. 2006, 128, 5998. (e) Zhou, J.;
He, J.; Wang, B.; Yang, W.; Ren, H. J. Am. Chem. Soc. 2011, 133, 6868.
(f) Shintani, R.; Otomo, H.; Ota, K.; Hayashi, T. J. Am. Chem. Soc. 2012,
134, 7305.
(10) For selected examples: (a) Tian, Q.; Larock, R. C. Org. Lett. 2000, 2,
3329. (b) Bour, C.; Suffert, J. Org. Lett. 2005, 7, 653. (c) Mota, A. J.;
Dedieu, A.; Bour, C.; Suffert, J. J. Am. Chem. Soc. 2005, 127, 7171. (d)
Zhao, J.; Larock, R. C. J. Org. Chem. 2006, 71, 5340.
(11) For selected examples: (a) Huang, Q.; Fazio, A.; Dai, G.; Campo, M. A.;
Larock, R. C. J. Am. Chem. Soc. 2004, 126, 7460. (b) Lu, Z.; Hu, C.; Guo,
J.; Li, J.; Cui, Y.; Jia, Y. Org. Lett. 2010, 12, 480. (c) Piou, T.; Bunescu,
A.; Wang, Q.; Neuville, L.; Zhu, J. Angew. Chem. Int. Ed. 2013, 52, 12385.
(d) Wang, M.; Zhang, X.; Zhuang, Y. -X.; Xu, Y. -H.; Loh, T. -P. J. Am.
Chem. Soc. 2015, 137, 1341.
(12) Wang, L.; Pan, Y.; Jiang, X.; Hu, H. Tetrahedron Lett. 2000, 41, 725. [8c]
(13) For selected examples: (a) Baudoin, O.; Herrbach, A.; Gueritte, F. Angew.
Chem. Int. Ed. 2003, 42, 5736. (b) Barder, T. E.; Walker, S. D.; Martinelli,
J. R.; Buchwald, S. L. J. Am. Chem. Soc. 2005, 127, 4685. (c) Hitce, J.;
Retailleau, P.; Baudoin, O. Chem. Eur. J. 2007, 13, 792. (d) Mota, A. J.;
Dedieu, A. J. Org. Chem. 2007, 72, 9669.
(14) Kesharwani, T.; Larock, R. C. Tetrahedron 2008, 64, 6090.
(15) For more palladium migration types: (a) Zhao, J.; Campo, M.; Larock, R.
C. Angew. Chem. Int. Ed. 2005, 44, 1873. (b) Zhao, J.; Yue, D.; Campo,
M. A.; Larock, R. C. J. Am. Chem. Soc. 2007, 129, 5288. (c) Kesharwani,
T.; Verma, A. K.; Emrich, D.; Ward, J. A.; Larock, R. C. Org. Lett. 2009,
11, 2591.
(16) Campo, M. A.; Zhang, H.; Yao, T.; Ibdah, A.; McCulla, R. D.; Huang, Q.;
Zhao, J.; Jenks, W. S.; Larock, R. C. J. Am. Chem. Soc. 2007, 129, 6298.
(17) For recent report on the reversibility of vinyl to aryl 1,4-metal migration
within rhodium and iridium complexes: Ikeda, Y.; Takano, K.; Waragai,
M.; Kodama, S.; Tsuchida, N.; Takano, K.; Ishii, Y. Organometallics 2014,
33, 2142.
(18) For reviews on direct C-H borylation : (a) Ishiyama, T.; Miyaura, N. J.
Organomet. Chem. 2003, 680, 3. (b) Ishiyama, T.; Miyaura, N. Pure Appl.
Chem. 2006, 78, 1369. (c) Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.;
Murphy, J. M.; Hartwig, J. F. Chem. Rev. 2010, 110, 890. (d) Hartwig, J. F.
Chem. Soc. Rev. 2011, 40, 1992. (e) Hartwig, J. F. Acc. Chem. Res. 2012,
45, 864. (f) Ros, A.; Fernandez, R.; Lassaletta, J. M. Chem. Soc. Rev. 2014,
43, 3229.
(19) For selected recent examples on direct C-H borylation: (a) Dai, H.-X.; Yu,
J.-Q. J. Am. Chem. Soc. 2012, 134, 134. (b) Kawamorita, S.; Miyazaki, T.;
Iwai, T.; Ohmiya, H.; Sawamura, M. J. Am. Chem. Soc. 2012, 134, 12924.
(c) Ros, A.; Lopez-Rodriguez, R.; Estepa, B.; Alvarez, E.; Fernandez, R.;
Lassaletta, J. M. J. Am. Chem. Soc. 2012, 134, 4573. (d) Cho, S. H.;
Hartwig, J. F. J. Am. Chem. Soc. 2013, 135, 8157. (e) Kuninobu, Y.;
Iwanaga, T.; Omura, T.; Takai, K. Angew. Chem. Int. Ed. 2013, 52, 4431.
(f) Kallane, S. I.; Braun, T. Angew. Chem. Int. Ed. 2014, 53, 9311. (g)
Obligacion, J. V.; Semproni, S. P.; Chirik, P. J. J. Am. Chem. Soc. 2014,
136, 4133. (h) Zhang, L. -S.; Chen, G.; Wang, X.; Guo, Q. -Y.; Zhang, X.
-S.; Pan, F.; Chen, K.; Shi, Z. -J. Angew. Chem. Int. Ed. 2014, 53, 3899. (i)
Dombray, T.; Werncke, C. G.; Jiang, S.; Grellier, M.; Vendier, L.;
Bontemps, S.; Sortais, J.-B.; Sabo-Etienne, S.; Darcel, C. J. Am. Chem.
Soc. 2015, 137, 4062. (j) Kuninobu, Y.; Ida, H.; Nishi, M.; Kanai, M.
Nature Chem. 2015, 7, 712. (k) Legare, M. A.; Courtemanche, M. A.;
proceeded smoothly to afford
a trisubstituted alkene without any
detectable E/Z isomer. See support information for details.
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R'
R'
Pd(OAc)2 (5 mol %)
1
2
3
L (7.5 mol %)
B(pin)
Br
B2(pin)2, CsOAc,
THF, TBAB, 110 o
R
R
C
[Pd0]
4
5
6
B2(pin)2
R'
R'
1,4ꢀmigration
PdII
PdII
R
L = tris(4ꢀmethoxyphenyl)phosphine
R' = aryl, heteroaryl, alkyl, CO2Me, CN
7
8
R
9
+ First palladium migration to a vinyl position
+ First C-H borylation via metal migration
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