.
Angewandte
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However, treatment of 5 with Pd(OAc)2 in the presence of
PtBu3·HBF4 led to the ketone 6; the vinyl palladium
intermediate underwent a ß-hydride elimination and not the
the alkene 11b in 67% yield, and substrates 7a and 8d led to
alkene 11j in 77% yield (Scheme 3).
To determine the scope and limitations of this reaction we
used various aryliodides 7 bearing either a phenoxy (7a), a 2-
nitrophenoxy (7b), or a 4-nitrophenoxy (7c) moiety to
examine the influence of electronic and steric properties on
the process (Scheme 4). Moreover, we also changed the
substituents on the alkyne moiety (8a–d) and we even
introduced a heterocyclic component (8e) in this part. In all
cases we got good to excellent yields with up to 96%, as found
for 11k and 11l. In most of the examples the reaction
mixtures were heated to 1208C in a microwave reactor but, in
a few cases, that is for the synthesis of 11a, 11d, and 11j, the
reaction mixtures were heated at 1008C in an oil bath.
Although it was our intention to keep the catalytic system as
simple as possible, we also investigated the influence of other
ligands; only in the reaction of aryliodide 7b and alkyne 8a to
give 11b was a slightly better yield achieved when 1,1’-
bis(diphenylphosphanyl)ferrocene (dppf) was used as the
ligand instead of PPh3.
Products 11d–o were obtained as mixtures of E and
Z isomers, owing to fast isomerization of the double bond.[18]
In most of the cases, the Z configuration, where the naph-
thalene moiety and the substituent on the lower part are
opposite each other, is slightly preferred. Furthermore, the
influence of the substituents on the lower and upper part of
the substrates is not highly pronounced, although the use of
substrates with electron-withdrawing groups, such as NO2 and
CN, seems to improve the yields, whereas the position of the
À
desired C H activation (Scheme 2).
Scheme 2. Palladium-catalyzed transformation of 5 to give ketone 6.
The problem could be solved by using alkynes of type 9 as
À
substrates for the carbopalladation/C H activation domino
process, where a b-hydride elimination of the proposed vinyl
palladium intermediate 10 could not take place. Thus, the
desired helical alkene 11b could be obtained in 31% yield
from alkyne 9a in the presence of Pd(OAc)2, PPh3, and
K2CO3. However, initial attempts to generate substrate 9a by
a Sonogashira reaction of the aryliodide 7b and the alkyne 8a
under standard reaction conditions ([PdCl2(PPh3)2]/CuI/
NEt3) led exclusively to the homocoupling product (Table 1,
entry 1). Finally, by using a different base/solvent system we
were able to obtain the desired product 9a in good yield
(Table 1, entry 2). But, when these reaction conditions were
applied to substrates 7a and 8d the alkyne 9b was formed in
only 42% yield; when standard reaction conditions were used
the yield was 28% (Table 1, entries 3 and 4). Fortunately, by
applying copper-free conditions including a catalytic system
consisting of Pd(OAc)2/PPh3 in the presence of nBu4NOAc
the alkyne 9b was formed in 88% yield (Table 1, entry 5).
As the yield of the domino process of 9a was not
satisfactory and to improve the efficiency of the whole
À
reaction sequence we combined the carbopalladation/C H
activation domino process with the Sonogashira reaction to
give a two-component triple domino process.[15–17] Pleasingly,
reaction conditions similar to those employed for the
Sonogashira reaction of 7a and 8d could be used for the
domino transformations; the only changes required were
a higher temperature and the use of DMF as the solvent.
Under these reaction conditions a mixture of 7b and 8a gave
Table 1: Optimization of the coupling of aryl iodides 7 and alkynes 8 by
a Sonogashira reaction.
Entry Substrates Reaction conditions
Result[a]
1
2
3
7b+8a
7b+8a
7a+8a
[PdCl2(PPh3)2], CuI, NEt3, RT, 18 h homocoupling
product
[PdCl2(PPh3)2], CuI, nBu4NOAc,
1,4-dioxane, 608C, 35 min
9a (86%)
[PdCl2(PPh3)2], CuI, NEt3, RT, 17 h 9b (28%) +
homocoupling
product (46%)
4
5
7a+8d
7a+8d
[PdCl2(PPh3)2], CuI, nBu4NOAc,
1,4-dioxane, 608C, 19 h
9b (42%) +
homocoupling
product
Scheme 3. Sonogashira reaction of aryl iodide 7b and alkyne 8a to
À
give 9a followed by a carbopalladation/C H activation domino reac-
Pd(OAc)2, PPh3, nBu4NOAc,
1,4-dioxane, 608C, 2.5 h
9b (88%)
tion (right). Triple domino process for the synthesis of helical alkenes
11 from aryl iodides 7 and alkynes 8 (left). DMF=N,N’-dimethylform-
amide.
[a] Yield of the isolated product is given in parentheses.
2
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Angew. Chem. Int. Ed. 2013, 52, 1 – 5
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