Communications
Organocatalysis
Chalcogen Bonding Catalysis of a Nitro-Michael Reaction
Abstract: Chalcogen bonding is the non-covalent interaction
between Lewis acidic chalcogen substituents and Lewis bases.
Herein, we present the first application of dicationic tellurium-
based chalcogen bond donors in the nitro-Michael reaction
between trans-b-nitrostyrene and indoles. This also constitutes
the first activation of nitro derivatives by chalcogen bonding
(and halogen bonding). The catalysts showed rate accelera-
tions of more than a factor of 300 compared to strongly Lewis
acidic hydrogen bond donors. Several comparison experi-
ments, titrations, and DFT calculations support a chalcogen-
bonding-based mode of activation of b-nitrostyrene.
quinolines,[6c,d,13] and to a very recent report on the activation
of carbonyl compounds.[14] In particular, the activation of
nitro compounds has not been reported thus far for XB[15] or
ChB organocatalysis.
Herein, we present the first such activation of a nitro
derivative by ChB. To this end, the Michael addition of 5-
methoxyindole to trans-b-nitrostyrene (Scheme 1) was chosen
as a robust benchmark reaction.[16]
Non-covalent organocatalysis has thus far been dominated
by hydrogen bonding (HB), with primarily (thio)urea deriv-
atives being used as catalyst backbones.[1] Nonetheless, other
weak interactions such as anion–p interactions,[2] halogen
bonding (XB),[3] and chalcogen bonding (ChB)[4] have
attracted ever-increasing interest lately, and particularly the
first two modes are now also established in organocatalysis.[5]
In contrast, the application of ChB donors as intermolecular
Lewis acidic catalysts is a hardly explored concept, and first
examples were only published in 2017.[6] This is somewhat
surprising as ChB offers several potential advantages such as
its high directionality (with interaction angles of ca. 1808)[7]
and manifold options to fine-tune the binding strength (by
variation of the chalcogen substituent, the core structure, and/
or the second substituent on the chalcogen). Still, most
reports on ChB have thus far focused on its intramolecular
use,[8] on applications in supramolecular[9] and solid-state
chemistry,[10] as well as on anion recognition processes.[11]
ChB-based catalysts and activators were previously
mainly employed in halide abstraction reactions, in which
very Lewis basic anions act as substrates.[6a,b,12] The coordina-
tion of ChB donors to neutral compounds is surely weaker in
strength, and so their activation is more challenging (even
though the transition state may of course still be charged).
Indeed, this concept has hitherto been limited to a handful of
examples in which ChB donors enable the reduction of
Scheme 1. Benchmark reaction for catalyst activity: The reaction of
indole 1 with trans-b-nitrostyrene (2). DCM=dichloromethane.
In XB organocatalysis, neutral molecule activation has
mostly been achieved with iodine-based catalysts,[17] and the
heavier chalcogens are similarly known to produce stronger
noncovalent Lewis acids (Te > Se > S).[4,18] Interestingly, pre-
vious ChB catalysts were mostly based on S and Se, with the
very few examples of Te-based catalysts[11c,d,12b] being
restricted to neutral compounds[12b] or derivatives in which
the Te substituent is bound to a neutral moiety (in an overall
monocationic compound).[11c,d] In this study, we decided to
focus on dicationic bidentate selenium- and especially tellu-
rium-based compounds, to achieve maximum Lewis acidity.
Charged backbone structures are provided by triazolium units
as 1) their neutral analogues are stable compounds and
already strong anion acceptors[11c] and 2) the synthesis of
their cationic analogues should be feasible by simple alkyla-
tion.[11d] The second substituent on the chalcogen was chosen
to be phenyl in order to prevent a possible dealkylation of this
group by nucleophilic attack.[6a]
The synthesis of all compounds followed the same
strategy: Commercially available 1,3-diethynylbenzene (4)
was converted into 1,3-bis(triazole)benzene derivative 5 by an
azide–alkyne 1,3-dipolar cycloaddition reaction in quantita-
tive yield (Scheme 2).[19] Deprotonation with LDA in the
presence of the corresponding diphenyldichalcogenide pro-
vided neutral compounds 6Ch and—in the case of tellurium—
also the mono-chalcogenated analogue 8Ch.[20] In the final
alkylation step, several different counterions were introduced
to allow for a systematic investigation of their effect on
catalytic activity: Me3OBF4·Et2O, MeOTf, and MeNTf2 led
directly to the respective dicationic chalcogen bond donors
[*] P. Wonner, A. Dreger, L. Vogel, E. Engelage, Prof. Dr. S. M. Huber
Fakultꢀt fꢁr Chemie und Biochemie
Ruhr-Universitꢀt Bochum
Universitꢀtsstraße 150, 44801 Bochum (Germany)
E-mail: stefan.m.huber@rub.de
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
ꢂ 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.
F
4
7
,
Ch-X [6a,21] whereas BArF4 derivative 7Te-BAr was obtained by
anion exchange from 7Te-BF with TMABArF .[16d,21,22] To the
4
4
best of our knowledge, this is the first report on dicationic
Angew. Chem. Int. Ed. 2019, 58, 1 – 6
ꢀ 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!