Angewandte
Chemie
DOI: 10.1002/anie.201410342
Heterocycles
Rhodium(III)-Catalyzed Cyclative Capture Approach to Diverse
1-Aminoindoline Derivatives at Room Temperature**
Dongbing Zhao, Suhelen Vꢀsquez-Cꢁspedes, and Frank Glorius*
In memory of Ekkehard Winterfeldt
Abstract: A RhIII-catalyzed C–H activation/cyclative capture
approach, involving a nucleophilic addition of C(sp3)–Rh
species to polarized double bonds is reported. This constitutes
the first intermolecular catalytic method to directly access 1-
aminoindolines with a broad substituent scope under mild
conditions.
ses, moderate to poor yields, harsh reaction conditions, and
limited substrate scope. Moreover, indoline as the parent
heterocycle must be prepared in advance.[4] To date, no
intermolecular catalytic method is available to directly access
the 1-aminoindoline core.[5]
RhIII-catalyzed directed C–H functionalization has
emerged as a versatile synthetic approach to access complex
molecules.[6] Recently, several groups have demonstrated that
C(sp2)–Rh intermediates formed by insertion of alkynes into
the C–Rh bond could undergo Grignard-type addition to
ketone-, imine-, amide-, and ester-based directing groups
(Figure 2A).[7] However, the nucleophilic attack of C(sp3)–Rh
species, generated upon alkene insertion, to polarized double
bonds has never been reported, presumably due to problem-
atic preferential b-hydride elimination (Figure 2B).[8] We
wondered whether nucleophilic additions of C(sp3)–Rh
species to polarized unsaturated directing groups might be
possible if b-hydride elimination is inhibited. Herein, we
introduce diazenecarboxylate as a directing group to trigger
a new cyclative capture approach where alkenes undergo
insertion followed by intramolecular addition of the C(sp3)–
T
he 1-aminoindoline unit is prevalent in numerous commer-
cial drugs and biologically active compounds (Figure 1),[1] and
has also been widely utilized as a chemical feedstock to access
a large number of important skeletal motifs.[2] 1-Aminoindo-
lines are typically formed by the nitrosylation/reduction of
free indolines or by intramolecular amination.[3] These
methods suffer from disadvantages such as multistep synthe-
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Rh species to the N N bond to afford diverse 1-aminoindo-
lines without any external oxidants (Figure 2C). This reaction
proceeds at room temperature with a wide range of function-
alized substrates, and, moreover, has been extended to the
synthesis of pharmaceutically important 1-aminoindoles.
Besides disfavoring b-hydride elimination of the C(sp3)–
Rh species, two other potential difficulties must be overcome:
1) Even though 1,2-diaryl- and 1-alkyl-2-aryl-substituted
diazenes have been used as directing groups, diazene-
carboxylate has never been used as a directing group;[9]
Figure 1. Some biologically active 1-aminoindolines and -indoles.
=
2) Although the addition of organometallic reagents to N N
bonds has been reported,[10] it has not been observed in
[*] Dr. D. Zhao,[+] S. Vꢀsquez-Cꢁspedes,[+] Prof. Dr. F. Glorius
Westfꢂlische Wilhelms-Universitꢂt Mꢃnster
Organisch-Chemisches Institut
RhIII-catalyzed C–H activation. Furthermore, the issue of
=
regioselectivity in additions to N N bonds must also be
addressed.
Corrensstrasse 40, 48149 Mꢃnster (Germany)
E-mail: glorius@uni-muenster.de
[+] These authors contributed equally to this work.
We initially focused on the reaction of tert-butyl 2-
phenyldiazenecarboxylate 1a and n-butyl acrylate (2a) with
[(Cp*RhCl2)2] (2.5 mol%) in 1,2-dichloroethane (DCE,
1 mL). After extensive screening, we found that the tandem
[**] This work was supported by the Alexander von Humboldt
Foundation (D.Z.). Generous financial support by the European
Research Council under the European Community’s Seventh
Framework Program (FP7 2007–2013)/ERC Grant Agreement
25936, and by the DFG (Leibniz Award, SFB858 (S.V.C.)) is
acknowledged. We also thank Constantin G. Daniliuc for X-ray
crystallographic analysis and Dr. Chang Guo, Dr. Matthew Hop-
kinson, Dr. Mꢁlissa Boultadakis-Arapinis, and Tobias Gensch (all
WWU Mꢃnster) for helpful discussions.
À
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C H bond activation/N N bond addition occurred smoothly
in the presence of [{RhCp*Cl2}2] (2.5 mol%; Cp* = C5Me5)
and AgOAc (10 mol%) in a mixture of HOAc and DCE (1:3)
at room temperature for 24 h to afford 1-aminoindoline 3a in
88% yield. To confirm the structure, we further converted the
oily 3a to the corresponding 1-aminoindole which formed
single crystals suitable for X-ray analysis (see the Supporting
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2014, 53, 1 – 6
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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