Nickel-catalyzed sonogashira reactions of non-activated secondary alkyl bromides and iodides

Article abstract of DOI:10.1002/anie.201307069

A nicked reaction: The title reaction of terminal alkynes with non-activated secondary alkyl iodides and bromides was accomplished for the first time. This reaction provides a new and practical approach for the synthesis of substituted alkynes (see scheme; cod=cyclo-1,5-octadiene). Copyright

Full text of DOI:10.1002/anie.201307069

Angewandte
Chemie
DOI: 10.1002/anie.201307069
Cross-Coupling
Nickel-Catalyzed Sonogashira Reactions of Non-activated Secondary
Alkyl Bromides and Iodides**
Jun Yi, Xi Lu, Yan-Yan Sun, Bin Xiao, and Lei Liu*
Alkynes are recurring structural motifs in a variety of natural
products, bioactive molecules, and functional materials.[1]
Among the many methods for the synthesis of substituted
alkynes, the transition-metal-catalyzed Sonogashira coupling
the first nickel-catalyzed Sonogashira coupling of non-acti-
vated secondary alkyl bromides and iodides. This reaction
uses readily available bis(oxazoline) ligands and shows good
functional-group compatibility, thus enabling efficient syn-
has proven to be one of the most popular and efficient.[2]
thesis of a variety of substituted alkynes. Furthermore, we
2
3
À
À
While early studies focused on canonical C(sp) C(sp ) bond
achieved highly diastereoselective C(sp) C(sp ) cross-cou-
3
À
formation, recent attention has been paid to the C(sp) C(sp )
plings of terminal alkynes with 1,3- and 1,4-substituted
cyclohexyl iodides.
coupling of terminal alkynes with non-activated alkyl electro-
philes. In a pioneering study Fu et al. discovered that N-
heterocyclic carbene ligands could promote palladium-cata-
lyzed Sonogashira coupling of primary alkyl bromides and
iodides.[3] Later on Glorius and co-workers extended the work
of Fu to even more challenging substrates, that is, non-
activated secondary alkyl halides.[4] The work of the group of
Glorius represents an extraordinary example in palladium
chemistry, because palladium catalysts can usually promote
the coupling of primary, but not secondary alkyl electro-
philes.[5]
We started with the coupling of 1-octyne with iodocyclo-
hexane (Table 1). The protocol by Hu et al. was tested first,
and it did not afford any desired product (entry 1).[12] The
failure of the NiII pincer complex L1 was attributed to the
bulky NMe2 groups. Thus we tested a terpyridine ligand (L2)
which bears three planar N atoms.[14a] The desired product
was observed albeit in a low yield of 10% (entry 2). This
finding encouraged us to test bis(oxazoline) ligands. Gratify-
ingly iPr-PyBox (L3a) and Me-PyBox (L3b) improved the
yield to 25 and 31%, respectively (entries 3 and 4). After the
side chain of oxazoline was completely removed (L4a), the
yield increased to 39% (entry 5). We then screened the
solvent, base, and nickel catalyst (entries 9–11). Under the
optimal reaction conditions the GC yield reached 95% with
a yield of 88% upon isolation (entry 11). We also tested L4a,
having different para-substituents (L4b–c), a bis(oxazoline)
with a small bite angle (L5), and a bidentate oxazoline ligand
(L6), but the yield did not improve (entries 12–15). Further-
more, the reaction temperature could be lowered to À208C
while maintaining the yield at 90% (entry 16). Finally, control
experiments revealed that the reaction completely shut down
without the addition of nickel (entry 17), whereas the yield
fell to 15% if CuI was not added (entry 18).
In comparison to palladium, nickel is more often used to
mediate the cross-coupling of secondary alkyl electrophiles.
Extensive recent studies have described nickel-catalyzed
Suzuki–Miyaura,[6] Negishi,[7] Hiyama,[8] Kumada,[9] Stille,[10]
and Heck[11] reactions of secondary alkyl halides. It is
surprising that a nickel-catalyzed Sonogashira reaction of
non-activated secondary alkyl halides with terminal alkynes
has not been reported. Even for the nickel-catalyzed Sonoga-
shira coupling of primary alkyl halides, there is only one prior
report by Hu et al. who used pincer ligands.[12,13] In contin-
uation of our studies on transition-metal-catalyzed cross-
coupling reactions of aliphatic electrophiles,[14] we now report
Table 2 shows the scope of the new reaction. Many non-
activated secondary alkyl bromides and iodides can be
successfully converted into the desired products with
modest to high yields (32–89%) at room temperature. Both
alkyl and aryl alkynes are good substrates. Both cyclic and
acyclic alkyl halides can be transformed. Furthermore,
heterocycles such as thiophene, carbazole azetidine, pyrroli-
dine, and piperidine are tolerated in either of the two coupling
partners.
The reaction is compatible with many synthetically
relevant functional groups such as ether, fluoride, ketal,
amide, sulfonamide, carbamate, and amine groups. The
reaction can also tolerate some base-sensitive functional
groups such as ester, silyl, and nitrile groups. Some olefin-
containing substrates can afford the desired cross-coupling
products, and surprisingly, an unprotected OH group (3w)
can be tolerated in the reaction. An interesting substrate is
[*] J. Yi, B. Xiao, Prof. L. Liu
Key Laboratory of Bioorganic Phosphorus Chemistry &
Chemical Biology (Ministry of Education)
Department of Chemistry, Tsinghua University
Beijing 100084 (China)
and
State Key Laboratory for Oxo Synthesis and Selective Oxidation
Lanzhou Institute of Chemical Physics, Chinese Academy of
Sciences
730000 Lanzhou (China)
E-mail: lliu@mail.tsinghua.edu.cn
J. Yi, X. Lu, Y.-Y. Sun, Prof. L. Liu
Department of Chemistry
University of Science and Technology of China
Hefei 230026 (China)
[**] This study was supported by the “863” Program of the Ministry of
Science and Technology (2012AA02A700), the National Basic
Research Program of China (973 program, No. 2013CB932800), and
the NSFC (Nos. 21221062 and 21225207).
3k, which contains a boronate ester group, and it undergoes
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201307069.
3
À
À
the nickel-catalyzed C(sp) C(sp ) coupling with its C B bond
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

.
Angewandte
Communications
liquid ammonia.[15] Our tests showed that by using
L4a as a ligand, many primary alkyl bromides and
iodides could be coupled to terminal alkynes in
modest to good yields (47–90%) at room temper-
ature. By comparison, the reaction conditions of Hu
et al. for primary alkyl bromides required 1008C.[12]
Our catalyst system could convert some previously
challenging substrates into the desired products. For
instance, Hu et al. reported that propynamine was
not suitable for nickel-catalyzed Sonogashira reac-
tion of alkyl halides.[12] Under our reaction condi-
tions 4a was obtained in 65% yield. Hu et al. also
found that thioether and the 2-H of an indole were
not tolerated in their reactions, however, 4b and 4c
were successfully obtained here.[12] In addition,
Table 1: Nickel-catalyzed coupling of iodocyclohexane with 1-octyne.
Entry Ni catalyst
(10 mol%)
Ligand
Base
Solvent
3a
(15 mol%) (2.0 equiv) (2 mL)
Yield [%][a]
a primary alkyl bromide could selectively be con-
3
À
verted in the presence of a primary C(sp ) Cl or
1
2
3
4
5
6
7
8
L1 complex
–
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
DMAc
trace
10
25
31
39
3
À
a secondary C(sp ) Br bond. The reaction could also
NiBr2·diglyme L2
NiBr2·diglyme L3a
NiBr2·diglyme L3b
NiBr2·diglyme L4a
NiBr2·diglyme L4a
NiBr2·diglyme L4a
NiBr2·diglyme L4a
NiBr2·diglyme L4a
NiBr2·diglyme L4a
[Ni(cod)2]
[Ni(cod)2]
[Ni(cod)2]
[Ni(cod)2]
[Ni(cod)2]
[Ni(cod)2]
–
tolerate an aryl chloride or bromide. As to the
functional group compatibility, amine, thioether,
nitrile, silyl, ether, ketone, and ester groups were
tolerated. Primary alkyl iodides were also good
substrates for the reaction. Finally, when CH3I was
used (4p, 4q), the reaction could be employed for the
methylation of a terminal alkyne.[16]
32
DMAc/1,4-dioxane[b] 45
DMAc/DME[c]
DMAc/DME[d]
DMAc/DME[d]
DMAc/DME[d]
DMAc/DME[d]
DMAc/DME[d]
DMAc/DME[d]
DMAc/DME[d]
DMAc/DME[d]
DMAc/DME[d]
DMAc/DME[d]
53
68
82
9
10
11
12
13
14
15
16[f]
17
L4a
L4b
L4c
L5
95 (88[e])
52
Recently Knochel et al. reported palladium-cat-
alyzed diastereoselective cross-coupling of alkynyl
bromides with substituted cyclohexylzinc which
produced stereochemically defined alkynes with
1,3- or 1,4-remote stereocontrol.[17] Inspired by the
67
55
20
90
trace
15
L6
L4a
L4a
L4a
work of Knochel et al. we examined the stereocon-
3
À
18[g] [Ni(cod)2]
trol of the present nickel-catalyzed C(sp ) C(sp)
cross-coupling. Thus 4- or 3-substituted cyclohexy-
liodides (racemic) were subjected to the cross-
coupling with terminal alkynes in the presence of
the optimized catalyst system (Table 4). For 4-
substituted substrates, thermodynamically favored
trans-1,4-disubstituted cyclohexanes were formed
with good diastereoselectivities (90:10 to 97:3 d.r.,
Table 3). In contrast, for 3-substituted cyclohexylio-
[a] The reaction was carried out at room temperature for 24 h. Iodocyclohexane
(0.5 mmol) was added into 2 mL solvent with 2 mol% CuI. Yields determined by GC
analysis. [b] 0.4 mL DMAc and 1.6 mL 1,4-dioxane. [c] 0.4 mL DMAc and 1.6 mL
DME. [d] 0.2 mL DMAc and 1.8 mL DME. [e] Yield of isolated product. [f] Temper-
ature=À208C. [g] Without CuI. cod=cyclo-1,5-octadiene, DMAc=N,N-dimethyl-
acetamide, DME=dimethoxyethane.
intact. In addition, we observed selective intermolecular
dides, the thermodynamically preferred cis-1,3-disubstituted
cyclohexanes were obtained with high diastereoselectivities
(92:8 to 99:1). Finally, by using 3b-iodo-5-cholestene as
substrate we obtained the alkynylation product 5j in 63%
cross-coupling of a secondary alkyl iodide over of an intra-
3
À
molecular primary C(sp ) Cl group (3t). These features
make additional functionalization reactions possible at either
À
À
the C B or C Cl bond.
A trimethylsilyl-capped alkyne can be readily converted
into a terminal alkyne under mild reaction conditions. Thus by
using ethynyltrimethylsilane as the starting material
(Scheme 1), we could sequentially conduct two alkylation
reactions to synthesize a nonsymmetric alkyne having two
secondary alkyl substitutions. This particular process expands
the scope and flexibility of alkyne synthesis. Scheme 1 also
3
À
shows that the new nickel-catalyzed C(sp) C(sp ) coupling
could be conducted on gram scale.
The success of the above reactions inspired us to examine
their application to the cross-coupling of primary alkyl halides
(Table 3). Such cross-couplings may exhibit better functional-
group tolerance compared to that under the traditional
reaction of primary alkyl halides with alkynyl anions in
Scheme 1. Synthesis of disubstituted alkynes.
2
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
Table 2: Reaction scope with respect to the secondary alkyl halide and
terminal alkyne.[a]
Table 3: Reaction scope for the cross-coupling of primary alkyl halides.[a]
[a] 0.4 mL DMAc and 1.6 mL DME were used. 0.5 mmol alkyl bromide
was used. Yields of isolated products after 24 h reaction time.
[b] 0.5 mmol alkyl iodine was used. No CsI was added. [c] 2.0 equiv MeI
and 1.0 equiv alkynes were used. No CsI was added. Yields were based
on the alkynes. TMS=trimethylsilyl.
methyl)cyclopropane [Eq. (2)]. In this reaction we only
obtained the ring-opening product 7a in 65% yield upon
isolation.[19]
[a] 0.2 mL DMAc and 1.8 mL DME were used. The reactions were
conducted on a 0.5 mmol scale. Yields of isolated products after 24 h
reaction time. [b] Reaction conditions: 0.5 mmol alkyl bromides, 2 equiv
alkynes, 0.5 equiv KI, 0.6 mL DMF and 1.4 mL DME were used. The
reaction was carried out at 608C. Yields of isolated products after 24 h
reaction time. Boc=tert-butoxycarbonyl, Cbz=benzyloxycarbonyl,
TBS=tert-butyldimethylsilyl, Ts=4-toluenesulfonyl.
yield as a single diastereomer, whose structure was confirmed
by X-ray.
The above observations are consistent with a radical-type
mechanism which has been proposed for nickel-catalyzed
cross-coupling reactions.[20] In this mechanism, an alkynyl–NiI
complex is generated first, and then reacts with an alkyl halide
through a one-electron, ligand-based redox event to generate
a NiII species. An oxidative radical addition ensues to afford
the NiIII complex, which undergoes reductive elimination to
generate the desired product, leaving a NiI complex to enter
To examine the mechanism of the nickel-catalyzed
Sonogashira cross-coupling of alkyl halides, we tested the
reaction between 6-iodoheptene with hex-5-ynenitrile
[Eq. (1)]. We obtained 15% of the linear coupling product
8a, while the major product 8b (50% yield upon isolation)
revealed the involvement of a 5-exo cyclization process.[18]
Subsequently we also tested the cross-coupling of (bromo-
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
[a]
À
Table 4: Remote stereocontrol in C(sp3) C(sp) cross-coupling.
To summarize, in the present study we developed the first
practical procedure for nickel-catalyzed Sonogashira cross-
coupling of terminal alkynes with non-activated secondary
alkyl iodides and bromides. This new reaction provides
a useful approach to the synthesis of substituted alkynes (in
particular, dialkylated asymmetric alkynes) from readily
available substrates. The bis(oxazoline) family of ligands
was found to be effective for mediating nickel-catalyzed
3
À
C(sp) C(sp ) cross-couplings of both secondary and primary
alkyl halides under fairly mild reaction conditions (room
temperature to À208C). The new reaction exhibited good
compatibility with a variety of synthetically important func-
tional groups and therefore, could be used for the synthesis
and modifications of biologically relevant molecules. Fur-
À
thermore, high diastereoselectivities were observed in C(sp)
[a] 0.2 mL DMAc and 1.8 mL DME were used. The reactions were
conducted in 0.5 mmol scale. Yields of isolated products after 24 h
reaction time. The diastereoselectivities were measured by GC.
[b] Reaction at RT. [c] Reaction at 08C. [d] Reaction at À208C. [e] The
thermal ellipsoids are displayed in 30% probability.[21]
C(sp3) cross-couplings of terminal alkynes with 1,3- and 1,4-
substituted cyclohexyl iodides. Our next challenge is to
optimize the ligand to induce enantioselectivity in the
nickel-catalyzed C(sp) C(sp ) cross-coupling reactions of
3
À
secondary alkyl halides.
the next catalytic cycle. This radical-type mechanism is
À
Received: August 12, 2013
Published online: && &&, &&&&
consistent with the stereochemistry observed in the C(sp)
C(sp3) cross-couplings of terminal alkynes with 1,3- and 1,4-
substituted-cyclohexyl iodides. Furthermore, when TEMPO
((2,2,6,6-tetramethylpiperidin-1-yl)oxyl) was added as a radi-
cal trap, the present reaction with either a primary or
Keywords: alkynes · cross-coupling · halides · nickel ·
.
synthetic methods
secondary alkyl halide was completely shut down.
3
À
Finally, to use nickel-catalyzed C(sp) C(sp ) coupling for
the modification of biologically interesting compounds, we
tested the alkynylation of 1-deoxy-1-iodo-diacetonefructose
[Eq. (3)]. The desired product was isolated in 46% yield. In
addition, we tested the cross-coupling of ethisterone with 3b-
iodo-5-cholestene [Eq. (4)], and the desired product was
obtained in 52% yield despite the presence of unprotected
alcohol, ketone, and olefin groups in the reactants.
[1] a) J. Liu, J. W. Y. Lam, B. Z. Tang, Chem. Rev. 2009, 109, 5799;
b) H. K. Bisoyi, S. Kumar, Chem. Soc. Rev. 2010, 39, 264.
[2] a) K. Sonogashira in Handbook of Organopalladium Chemistry
for Organic Synthesis (Ed.: E.-i. Negishi), Wiley-Interscience,
New York, 2002, pp. 493; b) R. Chinchilla, C. Nꢀjera, Chem. Rev.
2007, 107, 874.
[3] M. Eckhardt, G. C. Fu, J. Am. Chem. Soc. 2003, 125, 13642.
[4] G. Altenhoff, S. Wurtz, F. Glorius, Tetrahedron Lett. 2006, 47,
2925.
[5] Sporadic examples for palladium-catalyzed cross-coupling of
secondary aliphatic electrophiles: a) K. S. Bloome, R. L. McMa-
hen, E. J. Alexanian, J. Am. Chem. Soc. 2011, 133, 20146; b) A.
Rudolph, N. Rackelmann, M. Lautens, Angew. Chem. 2007, 119,
1507; Angew. Chem. Int. Ed. 2007, 46, 1485; c) B. M. Monks, S. P.
Cook, J. Am. Chem. Soc. 2012, 134, 15297.
[6] a) A. S. Dudnik, G. C. Fu, J. Am. Chem. Soc. 2012, 134, 10693;
b) A. Wilsily, F. Tramutola, N. A. Owston, G. C. Fu, J. Am.
Chem. Soc. 2012, 134, 5794; c) S. L. Zultanski, G. C. Fu, J. Am.
Chem. Soc. 2011, 133, 15362; d) Z. Lu, A. Wilsily, G. C. Fu, J.
4
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
Am. Chem. Soc. 2011, 133, 8154; e) N. A. Owston, G. C. Fu, J.
Am. Chem. Soc. 2010, 132, 11908; f) Z. Lu, G. C. Fu, Angew.
Chem. 2010, 122, 6826; Angew. Chem. Int. Ed. 2010, 49, 6676.
[7] a) C. J. Cordier, R. J. Lundgren, G. C. Fu, J. Am. Chem. Soc.
2013, 135, 10946; b) J. Zhou, G. C. Fu, J. Am. Chem. Soc. 2003,
125, 14726; c) V.-B. Phapale, E. BuÇuel, M. Garcꢁa-Iglesias, D. J.
Cꢀrdenas, Angew. Chem. 2007, 119, 8946; Angew. Chem. Int. Ed.
2007, 46, 8790.
[8] a) N. A. Strotman, S. Sommer, Angew. Chem. 2007, 119, 3626;
Angew. Chem. Int. Ed. 2007, 46, 3556; b) D. A. Powell, G. C. Fu,
J. Am. Chem. Soc. 2004, 126, 7788.
[9] P. Ren, O. Vechorkin, K. Allmen, R. Scopelliti, X. Hu, J. Am.
Chem. Soc. 2011, 133, 7084.
H. Chen, L. Liu, J. Am. Chem. Soc. 2012, 134, 11124; c) C.-T.
Yang, Z.-Q. Zhang, Y.-C. Liu, L. Liu, Angew. Chem. 2011, 123,
3990; Angew. Chem. Int. Ed. 2011, 50, 3904.
[15] L. Brandsma, Preparative Acetylenic Chemistry, Elsevier,
Amsterdam, 1988.
[16] R. R. Schrock, Chem. Rev. 2002, 102, 145.
[17] a) T. Thaler, L.-N. Guo, P. Mayer, P. Knochel, Angew. Chem.
2011, 123, 2222; Angew. Chem. Int. Ed. 2011, 50, 2174; b) P. M. P.
Garcia, T. D. Franco, A. Orsino, X. Hu, Org. Lett. 2012, 14, 4286.
[18] Examples: a) H. Ohmiya, H. Yorimitsu, K. Oshima, J. Am.
Chem. Soc. 2006, 128, 1886; b) W. Affo, H. Ohmiya, T. Fujioka,
Y. Ikeda, T. Nakamura, H. Yorimitsu, K. Oshima, Y. Imamura, T.
Mizuta, K. Miyoshi, J. Am. Chem. Soc. 2006, 128, 8068.
[19] Examples: a) T. Hatakeyama, T. Hashimoto, Y. Kondo, Y.
Fujiwara, H. Seike, H. Takaya, Y. Tamada, T. Ono, M.
Nakamura, J. Am. Chem. Soc. 2010, 132, 10674; b) Y. Ikeda, T.
Nakamura, H. Yorimitsu, K. Oshima, J. Am. Chem. Soc. 2002,
124, 6514; c) A. Guꢂrinot, S. Reymond, J. Cossy, Angew. Chem.
2007, 119, 6641; Angew. Chem. Int. Ed. 2007, 46, 6521.
[20] a) G. D. Jones, J. L. Martin, C. McFarland, O. R. Allen, R. E.
Hall, A. D. Haley, R. Jacob Brandon, T. Konovalova, P. J.
Desrochers, P. Pulay, D. A. Vicic, J. Am. Chem. Soc. 2006, 128,
13175; b) T. J. Anderson, G. D. Jones, D. A. Vicic, J. Am. Chem.
Soc. 2004, 126, 8100; c) V. B. Phapale, D. J. Cꢀrdenas, Chem. Soc.
Rev. 2009, 38, 1598; d) C.-P. Zhang, H. Wang, A. Klein, C.
Biewer, K. Stirnat, Y. Yamaguchi, L. Xu, V. Gomez-Benitez,
D. A. Vicic, J. Am. Chem. Soc. 2013, 135, 8141; e) J. Breitenfeld,
J. Ruiz, M. D. Wodrich, X. Hu, J. Am. Chem. Soc. 2013, 135,
12004.
[10] D. A. Powell, T. Maki, G. C. Fu, J. Am. Chem. Soc. 2005, 127,
510.
[11] C. Liu, S. Tang, D. Liu, J. Yuan, L. Zheng, L. Meng, A. Lei,
Angew. Chem. 2012, 124, 3698; Angew. Chem. Int. Ed. 2012, 51,
3638.
[12] O. Vechorkin, D. Barmaz, V. Proust, X. Hu, J. Am. Chem. Soc.
2009, 131, 12078.
3
À
[13] Other types of transition metal-catalyzed C(sp) C(sp ) cou-
plings: a) J. Caeiro, J. P. Sestelo, L. A. Sarandeses, Chem. Eur. J.
2008, 14, 741; b) O. Vechorkin, A. Godinat, R. Scopelliti, X. Hu,
Angew. Chem. 2011, 123, 11981; Angew. Chem. Int. Ed. 2011, 50,
11777; c) T. Hatakeyama, Y. Okada, Y. Yoshimoto, M. Naka-
mura, Angew. Chem. 2011, 123, 11165; Angew. Chem. Int. Ed.
2011, 50, 10973; d) H. Ohmiya, H. Yorimitsu, K. Oshima, Org.
Lett. 2006, 8, 3093; e) G. Cahiez, O. Gager, J. Buendia, Angew.
Chem. 2010, 122, 1300; Angew. Chem. Int. Ed. 2010, 49, 1278.
[14] a) C.-T. Yang, Z.-Q. Zhang, H. Tajuddin, C.-C. Wu, J. Liang, J.-
H. Liu, Y. Fu, M. Czyzewska, P. G. Steel, T. B. Marder, L. Liu,
Angew. Chem. 2012, 124, 543; Angew. Chem. Int. Ed. 2012, 51,
528; b) C.-T. Yang, Z.-Q. Zhang, J. Liang, J.-H. Liu, X.-Y. Lu, H.-
[21] CCDC 962572 (5j) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via www.
ccdc.cam.ac.uk/data_request/cif
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

.
Angewandte
Communications
Communications
Cross-Coupling
A nicked reaction: The title reaction of
terminal alkynes with non-activated sec-
ondary alkyl iodides and bromides was
accomplished for the first time. This
reaction provides a new and practical
approach for the synthesis of substituted
alkynes (see scheme; cod=cyclo-1,5-
octadiene).
J. Yi, X. Lu, Y.-Y. Sun, B. Xiao,
L. Liu*
&&&& — &&&&
Nickel-Catalyzed Sonogashira Reactions
of Non-activated Secondary Alkyl
Bromides and Iodides
6
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
These are not the final page numbers!