Angewandte
Chemie
CÀC Coupling
Dehydrogenative Carbon–Carbon Bond Formation Using Alkynyloxy
Moieties as Hydrogen-Accepting Directing Groups
Yasunori Minami,* Tatsuro Kodama, and Tamejiro Hiyama*
Abstract: In the presence of a catalyst system consisting of
benzoquinone) or bases, and the vinyloxy groups resulting
from dihydrogenation of the alkynyloxy groups are highly
Pd(OAc) , PCy , and Zn(OAc) , the reaction of alkynyl aryl
2
3
2
[
6]
ethers with bicycloalkenes, a,ß-unsaturated esters, or hetero-
arenes results in the site-selective cleavage of two CÀH bonds
followed by the formation of CÀC bonds. In all cases, the
useful functional groups. Herein, we report a series of
dehydrogenative reactions between alkynyl aryl ethers and
bicycloalkenes, a,ß-unsaturated esters, or heteroarenes. This
approach represents a convenient strategy for additive-free
catalytic cross-dehydrogenative CÀC bond-forming reactions.
alkynyloxy group acts as a directing group for the activation of
an ortho CÀH bond and as a hydrogen acceptor, thus rendering
the use of additives such as an oxidant or base unnecessary.
Recently, we reported that the reaction between triiso-
propylsilyl (TIPS)-substituted para-methoxyphenyl ether 1a
and norbornene (2a) in the presence of [Pd(PCy ) ] (5 mol%)
C
ross-dehydrogenative bond-forming reactions are highly
3
2
attractive methods in the toolbox of synthetic organic
chemistry, especially considering their potential in terms of
atom and step economy. Representative examples are the
cross-dehydrogenative formation of carbon–carbon, carbon–
and Zn (5 mol%) proceeds by ortho CÀH insertion/annula-
[5f]
tion to afford 4a. However, when the reaction between 1a
and 2a was carried out in the presence of Pd(OAc)2
(5 mol%), PCy (10 mol%), and Zn(OAc) (20 mol%) at
3
2
[1–3]
boron, and carbon-silicon bonds.
This concept also enables
1008C for 24 h, benzocyclobutene 3a with a Z-configured
silylethenoxy moiety was obtained in 75% yield, most likely
by the cleavage of the ortho and meta CÀH bonds (Table 1,
the custom-tailored construction of a variety of highly
functionalized compounds, and the site-selective cleavage of
two CÀH bonds and the subsequent removal of the eliminated
[7–10]
entry 1).
When the amount of 2a (1.5 equiv) was reduced,
hydrogen atoms are key factors in this context. To trap the
emitted hydrogen, several additives, such as olefins or
oxidants, have been successfully used, as the release of
dihydrogen only meets with difficulty. However, the use of
such additives may be problematic from a practical perspec-
tive, as they potentially interfere with the dehydrogenative
reaction.
3a was generated in a similar yield, albeit more slowly with
concomitant formation of the E isomer 3’a (entry 2). We also
examined other phosphine ligands, such as PBuAd2 and
XPhos, which also proved to be effective in this reaction. The
use of PBuAd afforded 3a and 3’a (91:9) in a combined yield
2
of 80%, whereas the use of XPhos provided 3a in 86% yield
(entries 3 and 4). The absence of Zn(OAc) resulted in the
2
Directing groups have been successfully employed for
formation of 3a in 49% yield, whereas the increased
formation of 4a (27%) suggested that the co-catalyst
[
4]
effective site- and regioselective CÀH functionalization. In
one of our previous studies, we demonstrated that alkynyloxy
groups (ÀOCꢀCR) are able to act as directing groups for the
activation of adjacent CÀH bonds, and subsequently engage
Zn(OAc) promotes the generation of 3. It should be noted
2
that no traces of the corresponding dihydrogenated adduct 5
or ethynyloxy-substituted benzocyclobutene 6 were observed.
This observation is consistent with the formation of a four-
membered cycle and subsequent dihydrogenation.
[
5]
in addition reactions. For example, the reaction with alkynes
furnishes chromene derivatives by sequential insertions into
[
5a]
ortho CÀH bonds. On the basis of these results, we expected
Next, the scope of the twofold CÀH cleavage reaction
that the alkynyloxy group might also be able to act as
with 2a using a suitable ligand, namely PCy , PBuAd , or
3
2
a hydrogen acceptor and enable the cleavage of two CÀH
XPhos, was examined, and the results are also summarized in
bonds, thus facilitating a dehydrogenative carbon–carbon
bond-forming reaction. Moreover, this synthetic approach
would avoid the use of additives, such as oxidants (e.g.,
Table 1. In the presence of PBuAd at a lower concentration
2
of 0.1m, tert-butyldiphenylsilyl (TBDPS)-substituted ethynyl
ether 1b furnished cyclization product 3b in 82% yield
[
11]
(
entry 5). Using XPhos, the substrate with a less bulky tert-
butyldimethylsilyl (TBDMS) group afforded 3c in lower yield
(entry 6). Aryl tert-butylalkynyl ether 1d could also be
converted into 3d in 51% yield in the presence of the
XPhos ligand (entry 7). Substrates with a cyclohexyl, methyl,
or phenyl group instead of the tert-butyl group attached to the
[
*] Dr. Y. Minami, Prof. Dr. T. Hiyama
Research and Development Initiative
Chuo University and JST, ACT-C
Kasuga, Bunkyo-ku, Tokyo 112-8551 (Japan)
E-mail: yminami@kc.chuo-u.ac.jp
[12]
ethynyl moiety were not suitable for this reaction. These
results suggest that a bulky substituent on the ethynyl carbon
atom is necessary for effective double CÀH cleavage. The
T. Kodama
Department of Applied Chemistry, Chuo University
Kasuga, Bunkyo-ku, Tokyo 112-8551 (Japan)
presence of para-, meta-, and ortho-substituted aryl groups in
the TIPS ethynyloxy moiety did not hamper the reaction
(entries 8–12). Silylethynyl 4-biphenyl ether 1i afforded 3i in
Angew. Chem. Int. Ed. 2015, 54, 11813 –11816
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
11813