.
Angewandte
Communications
DOI: 10.1002/anie.201403651
Gold Complexes
ACyclization–Rearrangement Cascade for the Synthesis of Structurally
Complex Chiral Gold(I)–Aminocarbene Complexes**
ˇ ´
Filip Kolundzic, Annamalai Murali, Patricia Pꢀrez-Galꢁn, Jonathan O. Bauer,
Carsten Strohmann, Kamal Kumar,* and Herbert Waldmann*
Dedicated to Professor George M. Whitesides on the occasion of his 75th birthday
Abstract: A facile synthesis of chiral cyclic alkyl amino-
carbene–gold(I) complexes from gold-free 1,7-enyne sub-
strates was developed. The novel cyclization–rearrangement
reaction sequence is triggered by the addition of (Me2S)AuCl to
different 1,7-enynes and leads to structurally unique carbene–
gold(I) complexes in high yields. These novel complexes are
catalytically active and inhibit the proliferation of different
human cancer cell lines.
exploration are in high demand. A frequently used synthesis
strategy employs the cyclization of metal-free precursors to
the corresponding carbene complexes of gold(I) and gold(III)
as the key step.[8] Although appealing, this strategy has not yet
yielded CAAC–gold(I) complexes. Previous syntheses of
CAAC–AuI complexes follow multistep protocols that
require the isolation of the free carbene, which has to be
bound to the metal center in a separate step, thus severely
limiting the scope to a few gold complexes.[6,9] The presence of
a stereogenic center at the C5 position next to the carbene
makes this class of carbenes unique and is highly important
for the stability and the catalytic properties of the carbene or
its metal complexes. Currently available synthesis methods do
not allow the introduction of sufficient structural diversity at
the quaternary carbon atom next to the carbene which limits
the possibilities to optimize the carbene or its metal
complexes for different applications. Here we report a novel
and efficient one-step procedure for the synthesis of chiral
CAAC–AuI complexes from simple gold-free precursors
through a mechanistically unique cyclization–rearrangement
sequence. This cascade transformation was serendipitously
discovered during efforts aimed at the synthesis of hexacyclic
compounds inspired by the alkaloid yohimbine by means of
gold-catalyzed annulation [Scheme 1, Eq. (1) versus Eq. (2)].
As depicted in Equation (3) (Table 1), the protocol for the
formation of CAAC–AuI complexes involves the treatment of
a 1,2-dichloroethane solution of ene-yne 1 with a solution of
(Me2S)AuCl under argon in the dark at 408C for the indicated
period of time. The cyclization substrate derived from the
tetrahydro-b-carboline moiety by formal derivatization of the
NH with a 2,4-hexadien-1-yl moiety (compound 1a) within
18 h cleanly delivered the CAAC–AuI complex 2a in 90%
yield (Table 1 and Figure 1). The apparent cyclization–
rearrangement cascade gives direct access to novel and
G
old carbene chemistry has undergone rapid growth in the
last decade[1] and carbene–gold complexes have found wide-
spread applications in catalysis,[2] supramolecular chemistry,[3]
liquid crystal research,[4] and medicinal chemistry.[5] The
replacement of traditionally employed N-heterocyclic car-
benes (NHC) in gold complexes by cyclic alkyl amino
carbenes (CAAC)[6] leads to a unique class of stable gold-
carbenes.[7] CAACs contain a s-donor sp3 carbon adjacent to
the carbene and they may coordinate transition metals better
than NHCs, thiazolidine, and P-heterocyclic carbenes
(PHCs). The steric bulk on the quaternary carbon a to the
carbene in CAAC–gold complexes further differentiates
them from gold complexes with other ligands, including
NHCs. Although, CAAC–Au complexes have shown promis-
ing properties and interesting reactivity profiles,[6–8] the field is
still in its infancy. Clearly, further synthetic developments
providing access to structurally diverse complexes and their
ˇ ´
[*] Dr. F. Kolundzic, Dr. A. Murali, Dr. P. Pꢀrez-Galꢁn, Dr. K. Kumar,
Prof. Dr. H. Waldmann
Max-Planck-Institut fꢂr molekulare Physiologie
Otto-Hahn-Strasse 11, 44227 Dortmund (Germany)
E-mail: kamal.kumar@mpi-dortmund.mpg.de
Dr. K. Kumar, Prof. Dr. H. Waldmann
Technische Universitꢃt Dortmund, Fachbereich Chemie
44221 Dortmund (Germany)
Dipl.-Chem. J. O. Bauer, Prof. Dr. C. Strohmann
Technische Universitꢃt Dortmund, Fakultꢃt Chemie, Anorganische
Chemie, Otto-Hahn-Strasse 6, 44221 Dortmund (Germany)
[**] This work was funded by the Max-Planck-Gesellschaft and European
Research Council under the European Union’s Seventh Framework
Programme (FP7/2007-2013) (ERC Grant no. 268309). F.K. thanks
the Alexander von Humboldt Foundation for a postdoctoral
fellowship and we thank Dr. Axel Choidas (Lead Discovery Center,
Dortmund) for the biological evaluation of the gold(I) carbene
complexes.
Supporting information for this article is available on the WWW
Scheme 1. Discovery of a novel cyclization–rearrangement that gives
access to chiral CAAC–AuI complexes.
8122
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 8122 –8126