Nucleophile-selective cross-coupling reactions with vinyl and alkynyl bromides on a dinucleophilic aromatic substrate

Article abstract of DOI:10.1002/ejoc.201500138

A nucleophile-selective cross-coupling reaction on an aromatic compound bearing two metal groups, Bpin and SnMe₃, has been developed. Previously, only aryl bromides and iodides could be used as electrophilic components, but in this work, the scope could be extended to vinyl and alkynyl bromides as electrophiles. This means that the roles typical in Sonogashira couplings or Heck reactions of the aromatic ring as the dielectrophile coupling to vinyl and alkynyl metal species are reversed, which presents a new tool for organic synthesis. The first nucleophilic site to react is the stannyl group, and subsequently, a Suzuki-Miyaura cross-coupling reaction can take place on the same molecule.

Full text of DOI:10.1002/ejoc.201500138

Job/Unit: O50138
/KAP1
Date: 26-02-15 14:24:43
Pages: 6
FULL PAPER
DOI: 10.1002/ejoc.201500138
Nucleophile-Selective Cross-Coupling Reactions with Vinyl and Alkynyl
Bromides on a Dinucleophilic Aromatic Substrate
Lu-Ying He,[a] Mathias Schulz-Senft,[a] Birk Thiedemann,[a] Julian Linshoeft,[a]
Paul J. Gates,[b] and Anne Staubitz*[a]
Keywords: Cross-coupling / Palladium / C–C coupling / Chemoselectivity / Sulfur heterocycles
A nucleophile-selective cross-coupling reaction on an aro-
matic compound bearing two metal groups, Bpin and SnMe3,
in Sonogashira couplings or Heck reactions of the aromatic
ring as the dielectrophile coupling to vinyl and alkynyl metal
has been developed. Previously, only aryl bromides and iod- species are reversed, which presents a new tool for organic
ides could be used as electrophilic components, but in this
work, the scope could be extended to vinyl and alkynyl
bromides as electrophiles. This means that the roles typical
synthesis. The first nucleophilic site to react is the stannyl
group, and subsequently, a Suzuki–Miyaura cross-coupling
reaction can take place on the same molecule.
duced by cross-coupling methods, we now focussed on es-
tablishing nucleophile-selective CCRs with halogenated
vinyl or alkynyl compounds.
Introduction
Cross-coupling reactions (CCRs) of organometallic com-
pounds R–M with organic compounds R–X have evolved
into powerful and general methodologies for carbon–
carbon bond formation.[1] CCRs pervade all areas of or-
ganic synthesis[2] from the construction of polymers,[3]
pharmaceuticals[4] to natural products. In many cases, func-
tional group tolerance is high, but to build up complex or-
ganic scaffolds, highly selective CCRs are essential. Re-
search on electrophile-selective CCRs [differentiating be-
tween R–X1 and R–X2 (X = I, Br, Cl, OTf, etc.)] has been
intensively pursued.[5] For Stille reactions, the order of reac-
tivity of halides is I Ͼ Br Ͼ Cl.[6] However, nucleophile-
selective CCRs with dimetallic (hetero)-aromatic substrates
have been very rarely examined.[7]
In our group, a nucleophile-selective one pot reaction
was developed recently on a new thiophene building block
that contains both a stannyl group and a boronic ester func-
tional group.[7c] Furthermore, this reaction was extended to
both nucleophile- and electrophile-selective CCRs with aro-
matic rings based on a thiophene building block.[7d] For
both reactions, excellent chemoselectivity was observed in
Stille CCRs with mono-halogenated or di-halogenated elec-
trophiles in high yields.
Results and Discussion
As a test reaction, dinucleophilic thiophene 1 was cross-
coupled with the commercially available β-bromostyrene
(2a/2aЈ = 8:1) in toluene at 80 °C under microwave condi-
tions with [Pd(PPh3)4] as the catalyst. After 1 h, the starting
material was completely consumed, and the products 3a
and 3aЈ were isolated in a combined yield of 36%. Although
the reaction was highly selective for the nucleophile and no
Suzuki–Miyaura cross-coupling occurred, two major
homocoupling byproducts, the biaryl 4 in a yield of 17%,
and 1,4-diphenylbutadiene 5 in yield of 10% were isolated.
Oxidative homocoupling reactions leading to byproducts
such as 4 may occur when oxygen is not rigorously ex-
cluded,[8] but the reactions were performed under nitrogen
with rigorous exclusion of air and a repeat experiment
yielded similar results. Ozawa and co-workers have recently
performed a thorough investigation into a similar reac-
tion:[9] When (E)-β-bromostyrene reacted with phenylbor-
onic acid under Suzuki cross-coupling conditions, they also
found substantial amounts of byproduct 5 as an E/Z mix-
ture and biphenyl. Their detailed mechanistic studies sug-
gested that oxidative addition of the (E)-β-bromostyrene to
the Pd-centre was followed by a metathesis reaction with
(E)-β-bromostyrene leading to the homocoupled styryl–
styryl species 5 and [Pd(L)2Br2]. The latter may be reduced
by the aryl–metal species present, giving rise to biaryl com-
pounds such as 4. This reactivity was not observed for (Z)-
β-bromostyrene, because of the higher stability of its oxi-
dative insertion product, (Z)-styryl-Pd(L)2Br, towards reac-
However, the two reactions could be carried out only
with aromatic electrophiles. As double and triple bonds are
also very important functional groups that can be intro-
[a] Otto Diels-Institute for Organic Chemistry, University of Kiel,
Otto-Hahn-Platz 4, 24098 Kiel, Germany
E-mail: astaubitz@oc.uni-kiel.de
http://www.otto-diels-institut.de/staubitz/
[b] School of Chemistry, University of Bristol,
Cantock’s Close, Bristol BS8 1TS, UK
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500138.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1

Job/Unit: O50138
/KAP1
Date: 26-02-15 14:24:43
Pages: 6
A. Staubitz et al.
FULL PAPER
tion with another equivalent of (Z)-β-bromostyrene. As the gave a good combined yield of 3a and 3aЈ of 66% (Table 1,
relative kinetic stabilities of the intermediates in a catalytic entry 2). The catalyst loading could be lowered to 1 mol-%,
cycle are highly dependent on the reaction conditions, it and the product was obtained in 97% yield (3a + 3aЈ,
seemed plausible that this reaction could be optimized to Table 1, entry 7). The reaction was also efficient at a lower
improve the yield of the product and minimize the amount temperature of 40 °C (Table 1, entry 8); whereas 20 °C led
of byproducts. Over 40 different reaction conditions were to very long reaction times (Table 1, entries 9 and 10).
screened (solvents, catalysts, temperature, catalyst loading, Moreover, at 40 °C, fewer homocoupled byproducts were
reaction time, concentration; for details see the Supporting observed than at 60 °C.
Information Table S1), all reactions were monitored and
quantified by gas chromatography (GC).
Based on these results, the best reaction conditions for
the nucleophile-selective CCR were a catalyst loading of
Conversion and yield were highly dependent on the [Pd(PPh3)4] as low as 1 mol-% in DMF as the solvent,
catalysts, solvents and temperature. It emerged that for bi- either at 40 °C or 60 °C. The next aim was to establish
dentate and/or very bulky ligands, in the catalysts whether these conditions would be suitable for a variety of
[Pd(dppe)Cl2], [Pd(OAc)2/SPhos], [Pd(dppf)Cl2] and vinyl (Table 2) and alkynyl bromides (Table 3) as electro-
[Pd(PtBu3)2], the yields were low (25, 30, 46 and 39% philes.
respectively, Table S1, entries 13–16) because considerable
Vinyl bromides were synthesized from corresponding α,
amounts of homocoupled byproducts 4 and 5 formed β-unsaturated carboxylic acids[11] or carboxaldehyde[12] in
alongside other non-identified byproducts. Presumably, the good yields (see Supporting Information for details). The
intermediate styryl–Pd(L)2Br species, which forms by oxi- alkynyl bromides were also easily available in high yields
dative addition, is very reactive towards vinyl bromides in from the corresponding terminal alkynes.[11] For both types
the case of catalysts with bulky ligands. This might be be- of electrophiles, all reactions were entirely nucleophile-selec-
cause in the products of the homocoupling reaction, i.e., tive (as detectable by GC–MS and NMR spectroscopy) and
the complex [PdL2Br2] and the byproducts 4 and 5, steric generally very tolerant towards the electrophiles used. In
strain can be released. Therefore, [Pd(PPh3)4] as the least the case of vinyl bromides, especially for electron-rich com-
hindered catalyst (up to three ligands dissociate)[10] proved pounds, good to excellent yields of the corresponding prod-
the most suitable catalyst for this reaction (Table 1). Solvent ucts were obtained at 40 °C (74–77%; Table 2, 3b, 3c and
screening of dioxane, toluene, THF, pyridine, acetonitrile 3e). However, the amine 3d could be isolated in only 43%
and DMF (Table 1, entries 1–6) showed that DMF was the yield because despite the higher temperature of 60 °C and
most suitable solvent, giving a combined yield of 3a + 3aЈ a significantly longer reaction time of 168 h, the conversion
of 95% at 60 °C (Table 1, entry 6). However, polarity of the to the product was low. Even longer reaction times did not
solvent cannot be the only parameter influencing the reac- improve the result, which may be caused by the binding of
tion, because the much less polar toluene, for example, also the amine to the Pd centre.[13] With electron-neutral electro-
Table 1. Optimization of reaction conditions.[a]
Entry
Solvent
Concentration
[mmol/mL]
Cat. loading
[mol-%]
T
[°C]
t
[h]
Conv.[b]
[%]
Yield [%][c]
3a
3aЈ
4
5
1
2
3
4
5
Dioxane
Toluene
THF
Pyridine
MeCN
DMF
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.5
5
5
5
5
5
5
1
1
5
5
60
60
60
60
60
60
60
40
20
20
17
17
17
17
17
17
17
17
17
65
83
91
94
93
100
100
100
96
40
93
51
59
73
37
43
83
86
86
12
70
5
7
8
3
10
12
11
4
0
1
3
9
6
16
22
2
0
6
3
14
14
0
6
7
DMF
2
0
8
DMF
1
0
9
DMF
0.5
1
0
10
DMF
0.5
4
0
[a] 1 (1.1 equiv.), 2 (1.0 equiv.). [b] Conversion is based on 2. [c] Determined by GC with triisopropylbenzene as the internal calibration
standard.
2
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O50138
/KAP1
Date: 26-02-15 14:24:43
Pages: 6
Nucleophile-Selective Cross-Coupling Reactions
philes, β-bromostyrene 3a and 2-(2-bromovinyl)-thiophene type 7 (see Supporting Information for details): If Kugel-
3f also gave good yields of 90%, albeit at 60 °C, i.e., 20 °C rohr distillation was not possible, then no pure products
higher than for electron-rich vinyl bromides. However, the could be obtained due to over-absorption onto silica gel,
reaction to form 3g required about seven times as long as possibly due to interactions of the vacant orbital on boron
3e, which can be attributed to the much greater steric hin- with nucleophilic moieties in silica gel.[14]
drance due to the additional phenyl group geminal to the
reacting centre. If the steric hindrance was instead provided
Table 3. Stille CCRs of alkynyl bromides.[a]
by a methyl group (product 3h), a longer reaction time of
144 h was required. Electron-deficient vinyl bromides gave
excellent yields of the products 3i, 3j and 3k in relatively
short reaction times of about 30 h (88, 83 and 82%, respec-
tively).
Table 2. Nucleophile-selective CCRs with various vinyl bromides.[a]
[a] The reactions to obtain 7a and 7b were performed at 40 °C, and
those for 7c–7e were performed at 60 °C. [b] As a 1:1 mixture with
the starting material 1. [c] Contains impurities, for details see the
Supporting Information.
After the chemoselective Stille CCR, the products still
contain a boronic ester functional group, which can be fur-
ther coupled with a second electrophile by a Suzuki–
Miyaura CCR. By merely adding K2CO3 as a base, water
and a second electrophile to the reaction mixture after com-
pletion of the Stille CCR, this could be accomplished. All
of these subsequent reactions were stirred at 100 °C for 6 h
(Table 4). This allowed the synthesis of 8a and 8b in yields
of 86 and 85%, respectively. The synthesis of 8b demon-
Table 4. Chemoselective one-pot CCRs of thiophene 1.[a]
[a] The reactions to obtain 3a, 3b, and 3d were performed at 40 °C.
The reaction was further analysed with respect to alkynyl
bromides as electrophilic coupling partners (Table 3). For
alkynyl bromides with a simple n-hexyl (6a) or phenyl sub-
stituent (6b), the reaction gave good yields of 64 and 84%,
respectively at 40 °C. However, the reaction with 6c (R =
TMS), only afforded 7c in a yield of 44% (and could only
be isolated as a 1:1 mixture with starting material 1, even
at a temperature of 60 °C and a significantly longer reaction
time of 168 h). Although no byproduct formation was ob-
served, the reactivity of the electrophilic component was
exceedingly low. For 6d and 6e, both reactions were com-
plete in 29 h at 60 °C, but the isolated yield was relatively
low. In these cases, the issue was not conversion, but purifi-
cation. Both products decomposed on a silica column, and
it was also not possible to purify them by Kugelrohr distil-
[a] i) 1 (1.0 equiv.), 2a + 2aЈ (1.0 equiv.) [Pd(PPh3)4] (1 mol-%),
DMF, 60 °C, 17 h. ii) Electrophiles (1.0 equiv.), K2CO3 (2.0 equiv.),
lation. This was a general observation for all products of H2O, 100 °C, 6 h. [b] Yields of isolated products.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3

Job/Unit: O50138
/KAP1
Date: 26-02-15 14:24:43
Pages: 6
A. Staubitz et al.
FULL PAPER
distillation or column chromatography (for details with respect to
specific electrophiles see the Supporting Information).
strates that the strategy of using a nucleophile-selective
cross-coupling reaction allows very easy access to non-sym-
metric di-stilbene-like materials. Aryl iodides can also be
General Procedure for Nucleophile-selective CCRs with Various Alk-
used as the second electrophile and in the case of 2l, the ynyl Bromides: A solution of 1 (373 mg, 1.00 mmol), the alkynyl
bromide (1.00 mmol), and [Pd(PPh3)4] (11.6 mg, 10.0 μmol, 1 mol-
%) in DMF (4 mL) was heated to 40 or 60 °C for a specific time
(for details with respect to specific electrophiles see the Supporting
Information). The mixture was filtered through a short plug of ce-
lite with n-hexane (500 mL) or diethyl ether (50 mL) as the solvent.
The solvent was removed in vacuo and the crude product was puri-
fied by Kugelrohr distillation or column chromatography (for de-
tails with respect to specific electrophiles see the Supporting Infor-
mation).
reaction is also highly electrophile selective as shown by the
high yield of 75%. In addition, no unselectively cross-cou-
pled byproduct could be detected by GC–MS or NMR
spectroscopy. The second Suzuki–Miyaura coupling was
also performed with an alkynyl bromide, 6b, but the yield
was lower in this case, reflecting the lower efficiency of such
substrates in cross-coupling reactions, as described above
(Table 4).
General Procedure for Chemo-selective One-pot CCR of Thiophene
1: A solution of 1 (186 mg, 500 μmol), β-bromostyrene (E/Z = 8:1;
91.0 mg, 500 μmol), and [Pd(PPh3)4] (5.78 mg, 5.00 μmol, 1 mol-%)
in DMF (4 mL) was heated to 60 °C for 17 h. Then the second
electrophile (500 μmol) in DMF (4 mL) was added to the solution
in one portion in addition to K2CO3 (138 mg, 1.00 mmol) in de-
gassed water (1 mL). The solution was heated to 100 °C for 6 h.
After the solution cooled down to 20 °C, the solution was diluted
with CH2Cl2 (8 mL) and filtered through a short plug of silica with
CH2Cl2 (250 mL). After removing the volatile components in
vacuo, the crude product was purified by column chromatography
(for details with respect to specific electrophiles see the Supporting
Information).
Conclusions
In conclusion, reaction conditions for a nucleophile-
selective CCR between vinyl and alkynyl bromides with a
dinucleophilic thiophene substrate were established. Al-
though homocoupling of the nucleophile and electrophile,
respectively, are potential competing reactions, careful op-
timisation of the reaction conditions led to a process in
which these side reactions could be largely suppressed in all
cases. These reactions are general with respect to a wide
variety of electrophiles. For vinyl bromides, all products
were obtained in good to excellent yields, although time
and temperature needed to be adjusted from case to case.
Alkynyl bromides proved more difficult electrophilic com-
ponents, mainly due to purification issues, which are appar-
ently intrinsic for these types of boronic ester containing
thiophene alkynyl groups. In both cases, the resulting prod-
ucts are extremely versatile building blocks: they still con-
tain a boronic ester that can be further coupled with a sec-
ond electrophile by a Suzuki–Miyuara cross-coupling in
one-pot reactions. Furthermore, the reactions with the alk-
ynyl bromides provide access to aromatic alkynyl com-
pounds, with a reversal of the roles of nucleophile and elec-
trophile compared with Sonogashira CCRs. This makes this
reaction a valuable alternative for volatile aromatic alkynyl
compounds, in cases where Sonogashira couplings fail or
are unselective. The main advantage of a nucleophile-selec-
tive cross-coupling reaction is that a further organometallic
site remains for subsequent functionalisation reactions. This
was also demonstrated: by merely adding water and a base,
a Suzuki–Miyaura reaction could be added to the reaction
sequence. Aryl bromides and iodides as well as vinyl brom-
ides and alkynyl bromides react under these conditions.
Acknowledgments
L. Y. H. thanks the China Scholarship Council (CSC) for a Ph. D.
scholarship and Prof. Zheng-Guo Zhang’s and Prof. Xiao-Ming
Fang’s support for her work.
[1] a) A. Suzuki, Chem. Commun. 2005, 4759–4763; b) C. L. Sun,
B. J. Li, Z. J. Shi, Chem. Commun. 2010, 46, 677–685.
[2] U. Kazmaier, M. Pohlman, Metal-Catalyzed Cross-Coupling
Reactions, Vol. 1, 2nd ed., Wiley-VCH, Weinheim, 2004.
[3] a) A. D. Schlueter, J. Polym. Sci., Part A 2001, 39, 1533–1556;
b) T. Yamamoto, Bull. Chem. Soc. Jpn. 2010, 83, 431–455.
[4] a) C. Torborg, M. Beller, Adv. Synth. Catal. 2009, 351, 3027–
3043; b) J. Magano, J. R. Dunetz, Chem. Rev. 2011, 111, 2177–
2250; c) M. L. Crawley, B. M. Trost, Applications of Transition
Metal Catalysis in Drug Discovery and Development: An Indus-
trial Perspective, John Wiley & Sons, Hoboken, 2012.
[5] a) G. Y. Cho, P. Remy, J. Jansson, C. Moessner, C. Bolm, Org.
Lett. 2004, 6, 3293–3296; b) S. H. Lee, B. B. Jang, Z. H. Kafafi,
J. Am. Chem. Soc. 2005, 127, 9071–9078; c) S. Shekhar, J. F.
Hartwig, Organometallics 2007, 26, 340–351; d) M. Mosrin, P.
Knochel, Chem. Eur. J. 2009, 15, 1468–1477; e) J. J. Peterson,
Y. C. Simon, E. B. Coughlin, K. R. Carter, Chem. Commun.
2009, 4950–4952; f) M. Kienle, A. Unsinn, P. Knochel, Angew.
Chem. Int. Ed. 2010, 49, 4751–4754; Angew. Chem. 2010, 122,
4860; g) A. Martins, D. A. Candito, M. Lautens, Org. Lett.
2010, 12, 5186–5188.
[6] N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457–2483.
[7] Nucleophile-selective reactions on aromatic compounds: a)
E. J. Roskamp, P. S. Dragovich, J. B. Hartung, S. F. Pedersen,
J. Org. Chem. 1989, 54, 4736–4737; b) D. R. Williams, A. A.
Shah, Chem. Commun. 2010, 46, 4297–4299; c) J. Linshoeft,
A. C. J. Heinrich, S. A. W. Segler, P. J. Gates, A. Staubitz, Org.
Lett. 2012, 14, 5644–5647; d) A. C. J. Heinrich, B. Thiedem-
ann, P. J. Gates, A. Staubitz, Org. Lett. 2013, 15, 4666–4669;
nucleophile-selective reactions on other tin/boron reagents: e)
F. Lhermitte, B. Carboni, Synlett 1996, 377–379; f) R. S. Cole-
man, M. C. Walczak, Org. Lett. 2005, 7, 2289–2291; g) R. S.
Experimental Section
General Procedure for Nucleophile-selective CCRs with Various
Vinyl Bromides: A solution of 1 (373 mg, 1.00 mmol), the vinyl
bromide (1.00 mmol), and [Pd(PPh3)4] (11.6 mg, 10.0 μmol, 1 mol-
%) in DMF (4 mL) was heated to 40 or 60 °C for a specific time
(for details with respect to specific electrophiles see the Supporting
Information). The mixture was filtered through a short plug of ce-
lite with n-hexane (500 mL) as the solvent. The solvent was re-
moved in vacuo and the crude product was purified by Kugelrohr
4
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O50138
/KAP1
Date: 26-02-15 14:24:43
Pages: 6
Nucleophile-Selective Cross-Coupling Reactions
Coleman, X. L. Lu, I. Modolo, J. Am. Chem. Soc. 2007, 129,
3826–3827; h) M. Altendorfer, D. Menche, Chem. Commun.
2012, 48, 8267–8269; nucleophile-selective reactions on other
boron/boron reagents: i) S. J. Lee, K. C. Gray, J. S. Paek, M. D.
Burke, J. Am. Chem. Soc. 2008, 130, 466–468; j) G. A. Mo-
lander, D. L. Sandrock, J. Am. Chem. Soc. 2008, 130, 15792–
15793; k) H. Noguchi, T. Shioda, C. M. Chou, M. Suginome,
Org. Lett. 2008, 10, 377–380; l) M. Tobisu, N. Chatani, Angew.
Chem. Int. Ed. 2009, 48, 3565–3568; Angew. Chem. 2009, 121,
3617; m) N. Iwadate, M. Suginome, J. Am. Chem. Soc. 2010,
132, 2548–2549; n) R. R. Singidi, T. V. Rajan-Babu, Org. Lett.
2010, 12, 2622–2625; o) E. M. Woerly, A. H. Cherney, E. K.
Davis, M. D. Burke, J. Am. Chem. Soc. 2010, 132, 6941–6943;
p) S. Fujii, S. Y. Chang, M. D. Burke, Angew. Chem. Int. Ed.
2011, 50, 7862–7864; Angew. Chem. 2011, 123, 8008; q) J. C. H.
Lee, R. McDonald, D. G. Hall, Nature Chem. 2011, 3, 894–
899; r) K. C. Gray, D. S. Palacios, I. Dailey, M. M. Endo, B. E.
Uno, B. C. Wilcock, M. D. Burke, Proc. Natl. Acad. Sci. USA
2012, 109, 2234–2239; s) L. Xu, S. Y. Ding, P. F. Li, Angew.
Chem. Int. Ed. 2014, 53, 1822–1826; t) ; L. Xu, P. F. Li, Synlett
2014, 25, 1799–1802; nucleophile-selective reactions on other
boron/zinc reagents: u) Y. Nagashima, R. Takita, K. Yoshida,
K. Hirano, M. Uchiyama, J. Am. Chem. Soc. 2013, 135, 18730–
18733; nucleophile-selective reactions on other silicon/boron
reagents: v) M. G. McLaughlin, C. A. McAdam, M. J. Cook,
Org. Lett. 2015, 17, 10–13.
C. Adamo, C. Amatore, I. Ciofini, A. Jutand, H. Lakmini, J.
Am. Chem. Soc. 2006, 128, 6829–6836.
[8]
[9]
M. Wakioka, M. Nagao, F. Ozawa, Organometallics 2008, 27,
602–608.
[10]
a) M. Ahlquist, P. Fristrup, D. Tanner, P. O. Norrby, Organo-
metallics 2006, 25, 2066–2073; b) Z. Li, Y. Fu, Q. X. Guo, L.
Liu, Organometallics 2008, 27, 4043–4049.
a) J. P. Das, S. Roy, J. Org. Chem. 2002, 67, 7861–7864; b) R. A.
Fursule, P. O. Patil, B. D. Shewale, S. B. Kosalge, P. K.
Deshmukh, D. A. Patil, Chem. Pharm. Bull. 2009, 57, 1243–
1245.
[11]
[12] A. Hayford, J. Kaloko, S. El-Kazaz, G. Bass, C. Harrison, T.
Corprew, Org. Lett. 2005, 7, 2671–2673.
[13] a) Y. Li, M. A. El-Sayed, J. Phys. Chem. B 2001, 105, 8938–
8943; b) J. H. Li, W. J. Liu, Org. Lett. 2004, 6, 2809–2811.
[14] S. Hitosugi, D. Tanimoto, W. Nakanishi, H. Isobe, Chem. Lett.
2012, 41, 972–973.
Received: January 28, 2015
Published Online: ᭿
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5

Job/Unit: O50138
/KAP1
Date: 26-02-15 14:24:43
Pages: 6
A. Staubitz et al.
FULL PAPER
Cross-Coupling
L.-Y. He, M. Schulz-Senft,
B. Thiedemann, J. Linshoeft, P. J. Gates,
A. Staubitz* ...................................... 1–6
Nucleophile-Selective Cross-Coupling Re-
actions with Vinyl and Alkynyl Bromides
on a Dinucleophilic Aromatic Substrate
A nucleophile-selective one-pot cross-cou-
pling reaction on an aromatic compound
bearing both a stannyl group and a boronic
ester has been developed with vinyl and
alkynyl bromides as electrophiles, ex-
ploiting the different reactivity of the Stille
and Suzuki–Miyaura cross-coupling reac-
tions. The typical roles of the aromatic ring
as the dielectrophile coupling to vinyl and
alkynyl metal species are reversed, which
presents a new tool for organic synthesis.
Keywords: Cross-coupling / Palladium / C–
C coupling / Chemoselectivity / Sulfur het-
erocycles
6
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0