Communications
Metathesis
Nickel-Catalyzed Inter- and Intramolecular Aryl Thioether Metathesis
by Reversible Arylation
Abstract: A nickel-catalyzed aryl thioether metathesis has
been developed to access high-value thioethers. 1,2-Bis(dicy-
clohexylphosphino)ethane (dcype) is essential to promote this
highly functional-group-tolerant reaction. Furthermore, syn-
thetically challenging macrocycles could be obtained in good
yield in an unusual example of ring-closing metathesis that
does not involve alkene bonds. In-depth organometallic studies
support a reversible Ni0/NiII pathway to product formation.
Overall, this work not only provides a more sustainable
alternative to previous catalytic systems based on Pd, but also
presents new applications and mechanistic information that are
highly relevant to the further development and application of
unusual single-bond metathesis reactions.
A
ryl thioethers are often found in natural products,[1]
pharmaceuticals,[2–4] materials,[5] photoinitiators,[6] and fra-
2
grances.[7] Thus, the manipulation of C(sp ) S bonds has
À
recently become an active research area in transition-metal
À
catalysis. The formation of C S bonds has greatly benefited
Scheme 1. Context of the work.
from the advent of modern cross-coupling reactions, and
a wide variety of electrophilic precursors can now be readily
employed to generate complex aromatic thioethers, using
a diverse range of metal catalysts such as Pd,[8a–c] Cu,[9] and
single-bond metathesis process[12,13] (Scheme 1c). However,
the previously reported Pd-based catalytic system exhibited
several limitations with regards to potential applications:
1) the cost of the Pd precatalyst can be prohibitive for larger-
scale reactions;[14] 2) the scope with respect to the alkyl thiols
was limited to unfunctionalized compounds, thus precluding
many synthetic applications such as ring-closing reactions;
3) the lack of mechanistic information about the reaction
limits further catalyst development.
Ni.[10a–c] (Scheme 1a). In contrast, the cleavage of C S bonds
À
under catalytic conditions has only recently become a subject
of intense research efforts in catalysis (Scheme 1b). In these
reactions, the thioether group can effectively act as an
alternative to traditional cross-coupling handles such as
(pseudo)halogens, thereby providing new approaches to
synthesize and derivatize complex synthetic intermediate-
s.[11a–h]
We have recently introduced a new concept for the
manipulation of thioethers that involves both the formation
and cleavage of carbon–sulfur bonds through a reversible
À
Herein, we report a nickel system for the C S bond
metathesis of a broad range of functionalized coupling
partners (Scheme 1d). The improved reactivity of the Ni
system was key to developing the first example of a ring-
À
closing metathesis reaction of C S bonds that enables rapid
access to synthetically challenging macrocycles. The isolation
and characterization of three catalytically competent com-
plexes provide clear support for a Ni0/NiII catalytic cycle.
We began our investigation using Ni(COD)2 as a precata-
lyst and thioanisole and cyclohexanethiol as benchmark
substrates. Initial evaluation of different ligands led to the
recovery of starting materials (see Table S1 in the Supporting
Information). After detecting the metathesis product in 8%
yield after using Xantphos as a ligand, we evaluated several
other bidentate phosphine ligands. The combination of a 1,2-
bis(dicyclohexylphosphino)ethane (dcype) ligand and Ni-
(COD)2 (5%) gave the best result, with the product obtained
in 95% yield.[15a–c]
[*] T. Delcaillau, Dr. A. Bismuto, Prof. Dr. B. Morandi
Laboratorium fꢀr Organische Chemie, ETH Zꢀrich
Vladimir-Prelog-Weg 3, HCI, 8093 Zꢀrich (Switzerland)
E-mail: bill.morandi@org.chem.ethz.ch
T. Delcaillau, Dr. Z. Lian, Prof. Dr. B. Morandi
Max-Planck-Institut fꢀr Kohlenforschung
Kaiser-Wihelm-Platz 1, 45470 Mꢀlheim an der Ruhr (Germany)
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
ꢁ 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co.
KGaA. This is an open access article under the terms of the Creative
Commons Attribution Non-Commercial NoDerivs License, which
permits use and distribution in any medium, provided the original
work is properly cited, the use is non-commercial, and no
modifications or adaptations are made.
A wide range of thioanisole derivatives worked efficiently
with the Ni catalyst (Table 1). Indeed, electron-neutral (3aa,
Angew. Chem. Int. Ed. 2019, 58, 1 – 6
ꢀ 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
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