Angewandte
Chemie
DOI: 10.1002/anie.201301057
Homogeneous Catalysis
Gold-Catalyzed Cyclizations of cis-Enediynes: Insights into the Nature
of Gold–Aryne Interactions**
Youliang Wang, Akop Yepremyan, Subir Ghorai, Robert Todd, Donald H. Aue,* and
Liming Zhang*
ortho-Benzynes[1] and ortho-arynes[2] are reactive and versa-
tile intermediates in organic synthesis.[3] Their diverse
chemistry has been further enriched by the formation of
metal aryne complexes.[3b,4] They are mostly generated by
elimination of two adjacent groups or atoms on the arene ring.
The elimination strategy, however, can be synthetically
limiting because of difficulties in accessing suitably substi-
tuted arenes, demanding reaction conditions, and operational
hazards. A notable exception is a de novo aryne formation by
intramolecular hexadehydro Diels–Alder reactions.[5]
could either be trapped by weak nucleophiles or undergo
À
intramolecular C H insertions by a-carbene gold carbene
mesomers.
In our attempt to generate gold aryne complexes, we
reasoned that an aryne could be formed upon the addition of
À
a deprotonated terminal alkyne to the other C C triple bond
in a cis-enediyne substrate with the assistance of a metal
catalyst (Scheme 1a). Notable in this design is that the
Considering that the coordination of alkynes to gold
complexes often serves as the point of entry into versatile gold
catalysis,[6] it is notable that an aryne has seldom served as the
substrate for gold catalysis. Although an aryne is highly
electrophilic as a result of its low lying LUMO, the HOMO of
benzyne was computed to have an energy level similar to that
of 2-butyne.[7] Hence, it is not unreasonable to anticipate that
the interaction between electrophilic gold complexes and
arynes would be plausible. In fact, the study by Zhang and co-
workers[8] has invoked a benzyne gold complex, but the
interaction between in situ generated benzyne and
[Ph3PAuCl] is not clearly defined and leaves some doubt
about its existence. In contrast, another study[9] used in situ
generated benzyne to trap a gold intermediate en route to
anthracene derivatives, wherein no interaction between gold
and benzyne is proposed. We envisioned that gold–aryne
interactions, if understood, could serve to advance gold
catalysis. Herein, we disclose a study inferring that the
interaction between a cationic gold complex and an aryne
(i.e., a gold aryne complex) is a transition state and leads to
regioisomeric ortho-aurophenyl cation intermediates, which
Scheme 1. New approach to the aryne moiety and metal aryne
complexes.
À
strained C C triple bond in the aryne originates from the
terminal alkyne in the substrate and, in contrast to the typical
elimination approach, is formally not the bond formed. To
implement it, we envisioned that an additional metal could
facilitate the pivotal cyclization,[10] as shown in Scheme 1b,
thereby potentially leading to the generation of a metal aryne
complex. Moreover, we reasoned that a cationic gold(I)
complex could serve as both the metal catalysts M1 and M2. It
is well established that gold complexes can activate carbon–
carbon triple bonds efficiently and, at the meantime, alky-
nylgold can be readily formed in situ upon reaction with
terminal alkynes.[11]
[*] Y. Wang, A. Yepremyan, Prof. Dr. D. H. Aue, Prof. Dr. L. Zhang
Department of Chemistry and Biochemistry, University of California
Santa Barbara, CA (USA)
E-mail: aue@chem.ucsb.edu
We[11] have recently reported the generation of gold
vinylidenes (i.e., Aben) from benzene-1,2-dialkynes through
a highly regioselective, gold-promoted 5-endo-dig cyclization
(Scheme 2a).[12] DFT calculations for the energy surface
revealed that Aben was formed by a bifurcation mechanism in
competition with the a-auronaphthyl cation Bben from a 6-
endo-dig cyclization[13] (see the Supporting Information of
that work). Moreover, Bben rearranges to its more stable
structural isomer Cben through a low-energy-barrier gold
migration. The calculation also predicted the formation of the
Dr. S. Ghorai, Dr. R. Todd
Catalysis Research and Development, Sigma–Aldrich Chemical
Corp., Milwaukee, WI (USA)
[**] L.Z. thanks the NSF (CAREER CHE-0969157 and CHE-1301343) and
NIGMS (R01 GM084254) for generous financial support. D.H.A.
acknowledges support from the Center for Scientific Computing at
the CNSI and MRL (NSF MRSEC DMR-1121053 and NSF CNS-
0960316), as well as the National Center for Supercomputing
Applications (NSF TG-CHE100123) utilizing the NCSA Gordon and
Blacklight systems.
gold carbene intermediate Eben from Cben upon carbene
3
À
C(sp ) H insertion in the next step, thereby indicating the
Supporting information for this article is available on the WWW
contribution of a mesomeric a-carbene gold carbene (i.e.,
Angew. Chem. Int. Ed. 2013, 52, 7795 –7799
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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