Alkenylation of C(sp3)?H Bonds by Zincation/Copper-Catalyzed Cross-Coupling with Iodonium Salts

Article abstract of DOI:10.1002/anie.201713278

α-Vinylation of phosphonates, phosphine oxides, sulfones, sulfonamides, and sulfoxides has been achieved by selective C?H zincation and copper-catalyzed C(sp³)?C(sp²) cross-coupling reaction using vinylphenyliodonium salts. The vinylation transformation proceeds in high efficiency and stereospecificity under mild reaction conditions. This zincative cross-coupling reaction represents a general alkenylation strategy, which is also applicable for α-alkenylation of esters, amides, and nitriles in the synthesis of β,γ-unsaturated carbonyl compounds.

Full text of DOI:10.1002/anie.201713278

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Alkenylation of sp3 C-H Bonds by Zincation/ Copper-Catalyzed
Cross-Coupling with Iodonium Salts
Authors: Chuan Liu and Qiu Wang
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201713278
Angew. Chem. 10.1002/ange.201713278
Link to VoR: http://dx.doi.org/10.1002/anie.201713278
http://dx.doi.org/10.1002/ange.201713278

10.1002/anie.201713278
Angewandte Chemie International Edition
COMMUNICATION
Alkenylation of sp3 C–H Bonds by Zincation/Copper-Catalyzed
Cross-Coupling with Iodonium Salts
Chuan Liua,b and Qiu Wanga,*
Abstract: α-Vinylation of phosphonates, phosphine oxides, sulfones, salts. Vinyliodonium salts are an attractive electrophilic vinylation
sulfonamides, and sulfoxides has been achieved by selective C–H
zincation and copper-catalyzed C(sp3)–C(sp2) cross-coupling
reaction using vinylphenyliodonium salts. The vinylation
transformation proceeds in high efficiency and stereospecificity
under mild reaction conditions. This zincative cross-coupling reaction
represents a general alkenylation strategy, which is also applicable
for a-alkenylation of esters, amides, and nitriles in the synthesis of b,
g-unsaturated carbonyl compounds.
reagent[7b, 8, 13] due to their low toxicity, air- and moisture-stability,
and high reactivity, despite being less explored than analogous
diaryliodonium salts.[14] In this work, we demonstrate that such a
zincative vinylation approach is modular and remarkably
effective for a wide scope of sp3 C–H bonds under mild
conditions. The use of chiral zinc base has been explored
toward the development of asymmetric vinylation reactions.
(a) Pd-catalyzed direct-group assisted C–H alkenylation
O
O
R3
[Pd]
R1
R2
R1
H
R3
HN
DG
X
+
Alkene-containing molecules are ubiquitously desirable targets.
Olefins are one of the most important functional groups and
have rich and robust chemistry that is integral to organic
synthesis and chemical science.[1] Therefore, the development
of effective methods for incorporating this functional group is an
important goal. Toward this, great attention has been focused on
developing C(sp3)–C(sp2) bond-formation reactions, such as the
reactions of alkyl halides,[2] alkyl organometallic compounds,[3]
carbonyl and imines,[4] and carboxylic acids[5]. On the other hand,
vinylation of sp3 C–H bonds represents an appealing direct
approach. For example, palladium-catalyzed b-C–H olefination
of amides has been achieved by a sophisticated directing-group
assisted strategy (Scheme 1a).[6] An elegant copper-catalyzed
a-alkenylation of aldehydes has been reported via the synergy
HN
DG
R4
additives
R4
R2
X = H or I
(b) Cu-catalyzed alkenylation of aldehydes via amine catalysis
O
O
R2
[Cu]
amine catalyst
H
X
+
H
H
R2
R1
R1
X = B(OH)2 or PhIOTf
(c) Pd- or Ni-catalyzed alkenylation via deprotonation
R2
O
O
[Pd] or [Ni]
LiHMDS
Cs2CO3
LiHMDS
R3
H
R2
R1
R1 R4
R2
R3
X
R4
[Pd]
[Pd]
R3
R3
O2N
O2N
H
H
R4
R2
X = I, Br or OTf
pyridyl
with amine catalysis (Scheme 1b).[7]-[8] Alternatively,
a
pyridyl
R1
deprotonative/transition metal-catalyzed vinylation approach has
been elegantly developed via in situ formed carbanion
nucleophiles. Examples include a-vinylation of ketones,[9]
nitromethane,[10] and pyridylmethyl ethers[11] (Scheme 1c). This
deprotonative strategy is attractive without the requirement of
directing groups, yet has received success only for relatively
acidic sp3 C–H bonds aforementioned. Nevertheless, in
comparison to related arylation reactions, vinylation reactions of
sp3 C–H bonds are underexplored.[12] With olefins as one of the
R1 R4
(d) Cu-catalyzed alkenylation via a general C–H zincation (this work)
R3
Ph
I
R1
R1
R1
R3
H
ZnCl
Zn(tmp)Cl•LiCl
OTf
R2
R2
R2
N
Cu(OTf)2
(O)n
S
O
O
P
Ph
EtO
O
O
P
Ph
Ph
EtO
Me2N
Me
RO
Me
R
R
R
R
most useful functional groups,
a
general and effective
Scheme 1. Transition-Metal-Catalyzed Alkenylation of sp3 C–H Bonds.
alkenylation strategy is greatly desired and valuable.
Here, we report an efficient a-vinylation method for
phosphonate, sulfone, sulfoxide, and carbonyl derivatives by a
modular C–H zincative/copper-catalyzed C(sp3)–C(sp2) cross-
coupling reaction using vinylphenyliodonium salts (Scheme 1d).
This approach utilizes Zn(tmp)Cl-mediated selective zincation of
various C(sp3)–H bonds, from which the resulting nucleophilic
organozinc intermediates could undergo a copper-catalyzed
C(sp3)–C(sp2) cross-coupling reaction with vinylphenyliodonium
We initially chose ethyldiphenylphosphine oxide (1a) and
trans-strenylphenyl iodonium salt (2a) as model substrates to
attempt the vinylation of sp3 C–H bond (Table 1). First, several
commonly
used
bases
were
tested
to
promote
deprotonative/copper-catalyzed vinylation with CuOTfŸ1/2PhMe
catalyst in THF at room temperature, in all of which 1a was
recovered with no vinylation product formed (Table 1, entries 1–
5). A series of tetramethylpiperidine (tmp)-derived bases[15]-[16]
were next examined, including Mg(tmp)ClŸLiCl, Zn(tmp)2Ÿ(LiCl)2
and Zn(tmp)ClŸLiCl (entries 6–8). Encouragingly, all afforded
desired product 3a, with Zn(tmp)ClŸLiCl most effective (entry 8).
Among different copper catalysts (entries 9–13), Cu(OTf)2
proved to be most effective to form 3a in 86% isolated yield
(entry 13). Furthermore, the formation of 3a was improved by
[a]
[b]
Dr. C. Liu, Prof. Dr. Q. Wang
124 Science Drive, French Family Science Center
Department of Chemistry, Duke University
Durham, North Carolina 27708 (USA)
Email: qiu.wang@duke.edu
o
Current address: HitGen Ltd.
increasing the reaction temperature to 50 C (entry 14), which
Tianfu Life Science Park, 88 South Keyuan Road
Chengdu 610041 (P.R. China)
was chosen as the standard conditions for subsequent studies.
This article is protected by copyright. All rights reserved.

10.1002/anie.201713278
Angewandte Chemie International Edition
COMMUNICATION
O
P
O
P
R2
1) Zn(tmp)Cl•LiCl, THF, 50 o
C
Ph
Ph
Ph
Note that only trace amounts of desired product 3a were
observed in the absence of a copper catalyst (entry 15).[17]
R2
H
I
+
2) Cu(OTf)2,THF, 50 o
C
Ph
Ph
OTf
R1
R1
1
2
3
Table 1. Condition optimization for a-vinylation of 1a.[a]
X
O
P
O
O
P
O
P
Ph
Ph
Ph
Ph
Ph
Ph
P
Ph
Bn
O
P
O
P
Ph
Ph
Ph
Ph
1) Base, THF, rt
2) Cu catalyst, rt
Ph
Ph
Ph
H
I
Ph
+
Me
H
Me
Me
Ph
Ph
OTf
Me
1a
Me
3a
3c, X = Cl, 90%
3d, X = OMe, 80%
3a, 87%
3b, 92%
3e, 60%
2a
O
P
O
P
O
P
O
P
entry
base
catalyst
3aa, yield (%)[b]
Ph
Ph
Ph
Ph
Ph
Me
C3H7
Br
Cl
Ph
Ph
Ph
1
KOH
CuOTfŸ1/2 PhMe
CuOTfŸ1/2 PhMe
CuOTfŸ1/2 PhMe
CuOTfŸ1/2 PhMe
CuOTfŸ1/2 PhMe
CuOTfŸ1/2 PhMe
CuOTfŸ1/2 PhMe
CuOTfŸ1/2 PhMe
CuCl
0
Me
Me
Me
Me
3g, 95%
3f, 78%
3h, 93%
3i, 81%
2
KOtBu
NaOMe
0
Scheme 2. a-Vinylation reactions of phosphine oxides with different
vinylphenyliodonium salts 2. Conditions: 1 (0.2 mmol), Zn(tmp)ClŸLiCl (0.3
mmol), 2 (0.24 mmol), Cu(OTf)2 (0.02 mmol), THF (2 mL). Isolation yields.
3
0
4
KHMDS
0
5
n-BuLi
0
O
P
O
P
R2
1) Zn(tmp)Cl•LiCl, THF, 50 o
C
EtO
EtO
Ph
R2
6
Mg(tmp)ClŸLiCl
Zn(tmp)2Ÿ(LiCl)2
Zn(tmp)ClŸLiCl
Zn(tmp)ClŸLiCl
Zn(tmp)ClŸLiCl
Zn(tmp)ClŸLiCl
Zn(tmp)ClŸLiCl
Zn(tmp)ClŸLiCl
47
H
I
+
2) Cu(OTf)2,THF, 50 o
C
EtO
EtO
OTf
R1
R1
7
29
4
2
5
8
83
O
O
P
O
P
O
P
EtO
EtO
EtO
EtO
P
Ph
Ph
Bn
Ph
Ph
9
80
EtO
EtO
EtO
EtO
Me
Bn
10
11
12
13
14 [d]
15
CuBr
81
5a, 95%
5b, 99%
5c, 97%
5d, 81%
X
Cu[CH3CN]4PF6
Cu(OAc)2
68
O
P
O
P
O
O
P
EtO
EtO
EtO
EtO
P
C4H9
Bn
EtO
EtO
EtO
EtO
66
Me
Me
Me
Me
5e, X = Cl, 85%
5f, X = OMe, 76%
Cu(OTf)2
92 (86)[c]
(87)[c]
trace
5g, 60%
5h, 63%
5i, 60%
Zn(tmp)Cl
Ÿ
LiCl
Cu(OTf)2
Scheme 3. a-Vinylation reactions of phosphonates. Conditions: 4 (0.2 mmol),
Zn(tmp)ClŸLiCl (0.3 mmol), 2 (0.24 mmol), Cu(OTf)2 (0.02 mmol), THF (2 mL).
Isolation yields.
Zn(tmp)ClŸLiCl
--
[a] Conditions: 1a (0.2 mmol), base (0.3 mmol), 2a (0.24 mmol), catalyst (10
mol %), THF (2 mL), rt. [b] Yields determined by 1H-NMR with CH2Br2 as an
internal standard. [c] Isolated yield. [d] Reaction run at 50 oC.
vinylphenyliodonium salt 2a, diethyl phosphonates 4a–4d all
formed 5a–5d efficiently. Particularly, the reaction with
cyclopropyl-substituted phosphonate 4d did not result in the
formation of any ring-opening byproducts, indicating the
vinylation step does not involve a radical intermediate. On the
other hand, different alkenylphenyliodonium salts are also viable
under standard conditions, providing desired phosphonates 5e–
5i bearing different alkenyl groups at the a-position.
Using this zincative/cross-coupling approach, we next looked
into α-vinylation of sulfone derivatives as a direct entry to allylic
sulfones, which are highly valuable with its utilities as versatile
building blocks and known biological activities[19] (Scheme 4).
Upon further optimization, CuBr was chosen as the catalyst for
the vinylation reactions of sulfones and sulfonamides at room
temperature.[20] The vinylation reaction is applicable to a variety
of sulfones, such as those bearing a-methyl, fluoro, or bromo
group in the formation of 7a–7d. Sulfonamides also participated
in the vinylation smoothly to give the desired products 7e–7f.
Different vinylphenyliodonium salt partners are compatible for
the successful formation benzyl- and propanyl-substituted vinyl
sulfones 7g and 7h, respectively.
With standard conditions established, the a-vinylation
reactions of phosphine oxide 1 was examined using different
vinylphenyliodonium
salts
(Scheme
2).
Note
that
diphenylphosphine oxides bearing one or no α-substituent group
were found compatible to afford vinylation products 3a and 3b in
excellent yields, while a-disubstituted phosphine oxide failed to
undergo zincation. When the reactions of 1a were explored with
vinyliodonium salts bearing different substituents on the phenyl
group, such as 4-position electron-withdrawing chloride and
electron-donating methoxy group, both readily formed the
desired products 3c and 3d. Alkyl substituted vinyliodonium salts
were well tolerated, such as benzyl, methyl and propyl groups
that were demonstrated in the formation of 3e, 3f, and 3g,
respectively. It is worth noting that halogens are tolerated to
give vinylation products 3h and 3i, thus allowing further
functionalization by transition-metal catalyzed cross-couplings.
We also examined the vinylation reactions of phosphonates, a
related class of important compounds having wide applications
from agriculture to medicine[18] (Scheme 3). In the reactions with
This article is protected by copyright. All rights reserved.

10.1002/anie.201713278
Angewandte Chemie International Edition
COMMUNICATION
O
S
O
S
(a)
R1
O
R1
O
R2
1) Zn(tmp)Cl•LiCl, THF, rt
Ph
1)
LiCl
R3
H
I
+
O
P
O
P
Ph
N
ZnCl
Ph
Ph
Ph
Ph
Ph
2) CuBr, THF, rt
H
I
Ph
OTf
THF, rt, 8 h
R2
6
R2
+
Ph
Ph
2
7
OTf
2) Cu(OTf)2, THF, 50 o
C
Me
1a
Me
3a
2a
O
O
O
S
O
S
Ph
Ph
Ph
Ph
66% (39% ee)
S
Ph
S
O
Ph
Ph
Bn
Ph
O
O
F
O
(b)
Me
H
Br
1)
LiCl
O
S
Ph
O
S
Ph
N
ZnCl
Ph
7a, 79%
7d, 54%
7b, 79%
7c, 85%
Ph
Ph
Ph
THF, -
40 oC, 8 h
Ph
I
H
+
O
O
O
2) Cu(OTf)2, THF, rt
OTf
Me
Me
O
S
O
S
O
S
O
N
Et2N
Ph
Ph
Ph
Ph
S
C3H7
6a
2a
7a
O
O
O
O
71% (65% ee)
Me
Me
Me
Me
7e, 75%
7f, 66%
7g, 64%
7h, 59%
Scheme 6. Synthesis of optically active a-vinylated phosphine oxide and
sulfone. Isolation yields. The ee% values determined by chiral HPLC analysis.
Scheme 4. a-Vinylation of sulfones and sulfonamides. Conditions: 6 (0.2
mmol), Zn(tmp)ClŸLiCl (0.3 mmol), 2 (0.3 mmol), CuBr (0.02 mmol), THF (2
mL). Isolation yields.
To further demonstrate synthetic utility of this general
vinylation strategy, representative vinylated compounds were
transformed into a broader range of functional molecules
(Scheme 7). For example, phosphine oxide 3a and phosphonate
5e underwent Horner-Wadsworth-Emmons reactions to form
trans-diene products 10 and 11, respectively. The treatment of
The applicability of this zincative/vinylation strategy was
investigated among other types of sp3 C–H bonds (Scheme 5).
Under standard conditions, sulfoxide 8a provided the α-
vinylation product 9a in 65% yield. α-Vinylation of nitrile
derivatives were successful for the formation of 9b and 9c. a-
Vinylation of tert-butyl acetate and N, N-dimethylacetamide were
also effective, forming ester 9d and amide 9e in good yields.
Note a-vinylation of ketones were ineffective under standard
conditions. Overall, the generality of this copper-catalyzed
vinylation demonstrated on a variety of sp3 C–H bonds suggests
its potential in constructing a wide range of vinyl-alkyl bonds.
phosphonate
5b
with
Lawesson’s
reagent
afforded
thiophosphonate 12 in 86% yield, another useful class of
molecules.[21] Furthermore, subsequent a-alkylation of
phosphonate 5b led to the formation of phosphonate 13
containing fully substituted a-carbon atom, which offers a
solution to the challenging a-disubstituted phosphonates under
this zincative/vinylation transformation.
Cl
1) Zn(tmp)Cl.LiCl, THF, 50 o
2) Cu(OTf)2, THF, 50 o
C
Ph
Ph
X
H
X
Ph
Ph
I
+
Ph
Ph
R1
R1
C
OTf
Me
Me
8
2a
9
10
11
(79%, E/Z > 20/1)
(72%, E/Z > 20/1)
O
S
NC
Ph
NC
9b, 38%
Ph
Ph
Ph
1) n-BuLi, THF
2) PhCHO
1) n-BuLi, THF
2) PhCHO
from 3a
X = Ph
from 5e
9a, 65%
9c, 99%
X = OEt
O
P
X
O
O
Ar
Ph
Ph
X
tBuO
Me2N
R
Lawesson's reagent
LDA, MeI
from 5b
X = OEt
from 5b
X = OEt
9d, 90%[a]
9e, 86%[a]
toluene, 90 o
C
THF, -40 o
C
Scheme 5. a-Vinylation reactions of sulfoxide, nitriles, ester and amide.
Conditions: (0.2 mmol), Zn(tmp)ClŸLiCl (0.3 mmol), 2a (0.24 mmol),
S
O
P
EtO
EtO
8
P
Ph
Ph
Cu(OTf)2 (0.02 mmol), THF (2 mL). Isolation yields. [a] reaction run at rt.
EtO
EtO
Bn Me
Bn
12
13
(86%)
(52%)
In our attempt to use chiral ligands to explore asymmetric
versions of the vinylation reaction, our initial investigations
remained unsuccessful. Alternatively, we examined the use of
chiral zinc bases for stereoselective control of vinylation in the
vinylation reaction of phosphine oxide 1a and sulfone 6a
(Scheme 6). Moderate stereoinduction was observed with
commercially available (R)-bis((R)-1-phenylethyl)amine-derived
zinc base. Although the stereoselectivity at the current stage
remains non-optimal, these initial results demonstrated the
potential of developing an asymmetric vinylation reaction for the
synthesis of optically active olefin-containing compounds.[20]
Further investigations of asymmetrical versions of the vinylation
reaction and the synthesis of optically active alkenyl-containing
molecules will be reported in the future.
Scheme 7. Representative transformations of vinylation phosphonates into
diverse skeletons.
In summary, we have developed an efficient vinylation method
for various sp3 C–H bonds. This transformation was achieved by
a one-pot C–H zincation and copper-catalyzed C(sp3)–C(sp2)
bond formation using electrophilic vinyliodonium salts. The
developed transformation is not only valuable and useful for a
rapid entry to alkene-containing compounds of importance in
pharmaceuticals and functional materials, but also presents a
general tactic for introducing diverse functional groups onto
similar skeletons.
This article is protected by copyright. All rights reserved.

10.1002/anie.201713278
Angewandte Chemie International Edition
COMMUNICATION
[10] R. Padilla-Salinas, R. R. Walvoord, S. Tcyrulnikov, M. C. Kozlowski,
Org. Lett. 2013, 15, 3966–3969.
Acknowledgements
[11] X. Yang, B.-S. Kim, M. Li, P. J. Walsh, Org. Lett. 2016, 18, 2371–2374.
[12] Radical vinylation reactions were also reported. see: (a) J. Li, J. Zhang,
H. Tan, D. Z. Wang, Org. Lett. 2015, 17, 2522–2525; (b) X. Liu, S. Sun,
Z. Meng, H. Lou, L. Liu, Org. Lett. 2015, 17, 2396–2399.
We acknowledge Duke University for the financial support to this
work. Q.W. is a fellow of the Alfred P. Sloan Foundation and a
Camille Dreyfus Teacher-Scholar.
[13] (a) E. Cahard, N. Bremeyer, M. J. Gaunt, Angew. Chem. Int. Ed. 2013,
52, 9284–9288; (b) D. Holt, M. J. Gaunt, Angew. Chem. Int. Ed. 2015,
54, 7857–7861; (c) M. V. Ivanova, A. Bayle, T. Besset, T. Poisson, X.
Pannecoucke, Angew. Chem. Int. Ed. 2015, 54, 13406–13410.
[14] For selected reviews, see: (a) M. Bielawski, B. Olofsson, Chem.
Commun. 2007, 2521–2523; (b) M. Bielawski, B. Olofsson, Org. Synth.
2009, 86, 308; (c) E. A. Merritt, B. Olofsson, Angew. Chem. Int. Ed.
2009, 48, 9052–9070; for selected examples, see: (d) R. J. Phipps, N.
P. Grimster, M. J. Gaunt, J. Am. Chem. Soc. 2008, 130, 8172–8174; (e)
C. Liu, W. Zhang, L.-X. Dai, S.-L. You, Org. Lett. 2012, 14, 4525–4527;
(f) S. Zhu, D. W. C. MacMillan, J. Am. Chem. Soc. 2012, 134, 10815–
10818; (g) A. Baralle, L. Fensterbank, J. P. Goddard, C. Ollivier, Chem.
Eur. J. 2013, 19, 10809–10813; (h) U. Farid, F. Malmedy, R. Claveau, L.
Albers, T. Wirth, Angew. Chem. Int. Ed. 2013, 52, 7018–7022; (i) Z.
Huang, Q. P. Sam, G. Dong, Chem. Sci. 2015, 6, 5491-5498.
Keywords: copper catalysis • iodonium salt • vinylation • sp3 C–
H functionalization
[1]
Selected reviews: (a) S. R. Chemler, D. Trauner, S. J. Danishefsky,
Angew. Chem. Int. Ed. 2001, 40, 4544–4568; (b) S. E. Denmark, C. R.
Butler, Chem. Commun. 2009, 20–33; (c) C. C. C. J. Seechurn, M. O.
Kitching, T. J. Colacot, V. Snieckus, Angew. Chem. Int. Ed. 2012, 51,
5062–5085.
[2]
For representative examples, see: (a) A. Rudolph, M. Lautens, Angew.
Chem. Int. Ed. 2009, 48, 2656–2670; (b) X. Dai, N. A. Strotman, G. C.
Fu, J. Am. Chem. Soc. 2008, 130, 3302–3303; (c) A. Krasovskiy, C.
Duplais, B. H. Lipshutz, Org. Lett. 2010, 12, 4742–4744; (d) S. Lou, G.
C. Fu, J. Am. Chem. Soc. 2010, 132, 5010–5011; (e) G. A. Molander, T.
Barcellos, K. M. Traister, Org. Lett. 2013, 15, 3342–3345; (f) A. H.
Cherney, S. E. Reisman, J. Am. Chem. Soc. 2014, 136, 14365–14368;
(g) J. Choi, P. Martin-Gago, G. C. Fu, J. Am. Chem. Soc. 2014, 136,
12161-12165; (h) K. A. Johnson, S. Biswas, D. J. Weix, Chem. Eur. J.
2016, 22, 7399–7402; (i) C. Qiu, K. Yao, X. Zhang, H. Gong, Org.
Biomol. Chem. 2016, 14, 11332–11335; (j) Y. Cai, A. D. Benischke, P.
Knochel, C. Gosmini, Chem. Eur. J. 2017, 23, 250–253; (k) J. Choi, G.
C. Fu, J. Am. Chem. Soc. 2012, 134, 9102–9105.
[15] For selected references, see: (a) M. L. Hlavinka, J. F. Greco, J. R.
Hagadorn, Chem. Commun. 2005, 5304-5306; (b) M. Uchiyama, Y.
Matsumoto, D. Nobuto, T. Furuyama, K. Yamaguchi, K. Morokuma, J.
Am. Chem. Soc. 2006, 128, 8748-8750; (c) M. L. Hlavinka, J. R.
Hagadorn, Organomet. 2007, 26, 4105-4108; (d) S. H. Wunderlich, P.
Knochel, Angew. Chem. Int. Ed. 2007, 46, 7685-7688; (e) S.
Wunderlich, P. Knochel, Chem. Commun. 2008, 6387-6389; (f) A.
Unsinn, M. J. Ford, P. Knochel, Org. Lett. 2013, 15, 1128-1131; (g) S.
Duez, A. K. Steib, P. Knochel, Org. Lett. 2012, 14, 1951-1953.
[3]
[4]
For selected reviews, see: (a) R. Jana, T. P. Pathak, M. S. Sigman,
Chem. Rev. 2011, 111, 1417–1492; (b) J. Zhou, G. C. Fu, J. Am. Chem.
Soc. 2003, 125, 12527–12530.
[16] (a) S. L. McDonald, Q. Wang, Angew. Chem. Int. Ed. 2014, 53, 1867–
1871; (b) S. L. McDonald, Q. Wang, Chem. Commun. 2014, 50, 2535–
2538; (c) C. Liu, Q. Wang, Org. Lett. 2016, 18, 5118–5121.
For selected reviews, see: (a) J. Montgomery, Angew. Chem. Int. Ed.
2004, 43, 3890–3908; (b) E. Skucas, M. Y. Ngai, V. Komanduri, M. J.
Krische, Acc. Chem. Res. 2007, 40, 1394–1401; for representative
examples, see: (c) R. R. Huddleston, H.-Y. Jang, M. J. Krische, J. Am.
Chem. Soc. 2003, 125, 11488–11489; (d) S. J. Patel, T. F. Jamison,
Angew. Chem. Int. Ed. 2004, 43, 3941–3944; (e) C.-Y. Zhou, S.-F. Zhu,
L.-X. Wang, Q.-L. Zhou, J. Am. Chem. Soc. 2010, 132, 10955–10957;
(f) C.-H. Wei, S. Mannathan, C.-H. Cheng, J. Am. Chem. Soc. 2011,
133, 6942–6944; (g) K. Nakai, Y. Yoshida, T. Kurahashi, S. Matsubara,
J. Am. Chem. Soc. 2014, 136, 7797–7800; (h) E. P. Jackson, J.
Montgomery, J. Am. Chem. Soc. 2015, 137, 958–963; (i) Y. Huang, R.-
Z. Huang, Y. Zhao, J. Am. Chem. Soc. 2016, 138, 6571–6576.
J. T. Edwards, R. R. Merchant, K. S. McClymont, K. W. Knouse, T. Qin,
L. R. Malins, B. Vokits, S. A. Shaw, D. H. Bao, F. L. Wei, T. Zhou, M. D.
Eastgate, P. S. Baran, Nature 2017, 545, 213–219.
[17] See the Supporting Information for the proposed mechanism and
related control experiments.
[18] (a) K. W. Pankiewicz, K. Malinowski, H. N. Jayaram, K. Lesiak-
Watanabe, K. A. Watanabe, Curr. Med. Chem. 1999, 6, 629–634; (b) A.
Khandazhinskaya, M. Yasko, E. Shirokova, Curr. Med. Chem. 2006, 13,
2953–2980; (c) W. J. Watkins, J. M. Chen, A. Cho, L. Chong, N. Collins,
M. Fardis, W. Huang, M. Hung, T. Kirschberg, W. A. Lee, X. Liu, W.
Thomas, J. Xu, A. Zeynalzadegan, J. Zhang, Bioorg. Med. Chem. Lett.
2006, 16, 3479–3483; (d) C. S. Demmer, N. Krogsgaard-Larsen, L.
Bunch, Chem. Rev. 2011, 111, 7981–8006; (e) C. Queffélec, M. Petit, P.
Janvier, D. A. Knight, B. Bujoli, Chem. Rev. 2012, 112, 3777–3807; (f) J.
L. Montchamp, Acc. Chem. Res. 2014, 47, 77–87.
[5]
[6]
[19] For examples, see: (a) M. Yamada, T. Ichikawa, M. Ii, K. Itoh, N.
Tamura, T. Kitazaki, Bioorg. Med. Chem. 2008, 16, 3941–3958; (b) J. D.
Wilden, J. Chem. Res. 2010, 541–548; (c) X. Chen, S. Hussain, S.
Parveen, S. Zhang, Y. Yang, C. Zhu, Curr. Med. Chem. 2012, 19,
3578–3604; (d) S. S. A. Shah, G. Rivera, M. Ashfaq, Mini-Rev. Med.
Chem. 2013, 13, 70–86; (e) F. Reck, F. Zhou, M. Girardot, G. Kern, C.
J. Eyermann, N. J. Hales, R. R. Ramsay, M. B. Gravestock, J. Med.
Chem. 2005, 48, 499–506; (f) A. El-Awa, M. N. Noshi, X. M. du Jourdin,
P. L. Fuchs, Chem. Rev. 2009, 109, 2315–2349.
(a) M. Wasa, K. M. Engle, J.-Q. Yu, J. Am. Chem. Soc. 2010, 132,
3680–3681; (b) K. J. Stowers, K. C. Fortner, M. S. Sanford, J. Am.
Chem. Soc. 2011, 133, 6541–6544; (c) S. Li, G. Chen, C.-G. Feng, W.
Gong, J.-Q. Yu, J. Am. Chem. Soc. 2014, 136, 5267–5270; (d) B. Wang,
C. Lu, S.-Y. Zhang, G. He, W. A. Nack, G. Chen, Org. Lett. 2014, 16,
6260–6263.
[7]
(a) J. M. Stevens, D. W. C. MacMillan, J. Am. Chem. Soc. 2013, 135,
11756–11759; (b) E. Skucas, D. W. C. MacMillan, J. Am. Chem. Soc.
2012, 134, 9090–9093.
[20] See the Supporting Information for addtional experimental data.
[21] (a) S. D. Rushing, R. P. Hammer, J. Am. Chem. Soc. 2001, 123, 4861–
4862; (b) L. Maier, Synth. React. Inorg. Met.-Org. Chem. 1976, 6, 133–
155.
[8]
[9]
J. Guo, L. Lin, Y. Liu, X. Li, X. Liu, X. Feng, Org. Lett. 2016, 18, 5540–
5543.
For selected examples, see: (a) J. Huang, E. Bunel, M. M. Faul, Org.
Lett. 2007, 9, 4343–4346; (b) L. Jiang, S. Weist, S. Jansat, Org. Lett.
2009, 11, 1543–1546; (c) T. Ankner, C. C. Cosner, P. Helquist, Chem.
Eur. J. 2013, 19, 1858–1871; (d) M. Grigalunas, T. Ankner, P.-O.
Norrby, O. Wiest, P. Helquist, J. Am. Chem. Soc. 2015, 137, 7019–
7022; (e) M. Grigalunas, P.-O. Norrby, O. Wiest, P. Helquist, Angew.
Chem. Int. Ed. 2015, 54, 11822–11825.
This article is protected by copyright. All rights reserved.

10.1002/anie.201713278
Angewandte Chemie International Edition
COMMUNICATION
COMMUNICATION
Chuan Liu and Qiu Wang*
Page No. – Page No.
Alkenylation of sp3 C–H Bonds by Zincation/
Copper-Catalyzed Cross-Coupling with
Iodonium Salts
Text for Table of Contents
α-Vinylation of phosphonates, phosphine oxides,
sulfones, sulfonamides, sulfoxides, and carbonyl
derivatives has been achieved effectively by a
one-pot C–H zincation and copper-catalyzed
C(sp3)–C(sp2) cross-coupling reaction using
vinylphenyliodonium salts under mild conditions.
This article is protected by copyright. All rights reserved.