Unusual Au(III)-catalyzed dimerization of benzoxazol-2-yloxy enynes: Formation of substituted 1,5-cyclooctadienes

Article abstract of DOI:10.1016/j.jorganchem.2008.09.011

Symmetric 1,5-cyclooctadienes were formed via Au-catalyzed dimerization of benzoxazol-2-yloxy enynes, involving double nucleophilic attacks of alkenylgolds toward allylic cations.

Full text of DOI:10.1016/j.jorganchem.2008.09.011

Journal of Organometallic Chemistry 694 (2009) 520–523
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Unusual Au(III)-catalyzed dimerization of benzoxazol-2-yloxy enynes: Formation
of substituted 1,5-cyclooctadienes
*
Xiaogen Huang, Liming Zhang
Department of Chemistry/MS216, 1664 North Virginia Street, Reno, NV 89557, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 23 June 2008
Received in revised form 14 August 2008
Accepted 1 September 2008
Available online 10 September 2008
Symmetric 1,5-cyclooctadienes were formed via Au-catalyzed dimerization of benzoxazol-2-yloxy eny-
nes, involving double nucleophilic attacks of alkenylgolds toward allylic cations.
Ó 2008 Elsevier B.V. All rights reserved.
Keywords:
Gold
Catalysis
Dimerization
1. Introduction
tion of the C–C triple bond, forming zwitterionic alkenylgold B.
This migration should be substantially facilitated by the transfor-
Homogeneous Au catalysis has recently attracted much atten-
tion in synthetic community not only because of the shattering
of old perceptions of the chemical inertness of gold but also the
plethora of versatile transformations that Au complexes can cata-
lyze [1–10]. Much of the novel reactivities of Au complexes start
mation of an imidate moiety into a thermodynamically much more
stable amide group [20]; moreover, the C–C double bond at the
propargylic position stabilizes the carbon cation via resonance.
We have previously advanced a novel concept of ‘Au-containing
all-carbon 1,n-dipoles’ and applied it in studying the generation
of 1,4-dipoles [21] and 1,3-dipoles [22] in [4 + 2] and [3 + 2] cyclo-
addition reactions, respectively. Intermediate B can be viewed as
another example of Au-containing all-carbon 1,4-dipoles, and it
is envisioned that dipole B could couple with various polarized
double bonds involving a key nucleophilic cyclization of the
Au–C(sp2) bond (i.e., from C to 2), yielding [4 + 2] adduct 2 (see
Scheme 2).
We began with enynyl carbinol 3, prepared in two steps from 2-
iodocyclohex-2-enone –[23] Due to the difficulty in synthesis and
handling of imidates [24], we decided to convert alcohol 3 into
benzoxazol-2-yloxy enyne 4 [25], where an imidoyloxy moiety is
embedded. Thus, alcohol 3, upon deprotonation, was reacted with
2-chlorobenzoxazole rather efficiently to give the desired enyne
product 4 after desilylation by TBAF.
To our surprise, treatment of enyne 4 with various Au catalysts
in the presence of a range of dipolarophiles including aldehydes,
imines, ethyl vinyl ether, methyl vinyl ketone did not give expected
[4 + 2] adducts. Interestingly, we observed in all these trials two
new spots. With no dipolarophile present, those two spots were
also observed. Subsequently, they were isolated in 32.5% and
7.5% yields, respectively, after enyne 4 was treated with 5 mol%
of dichloro(pyridine-2-carboxylato)gold(III) (5) [26] in 1,2-dichlo-
roethane at room temperature for 10 h. Spectroscopic studies of
these compounds revealed that (a) their 1H NMR spectra were
from efficient activation of
p systems, especially alkynes, followed
by attack of various inter-/intramolecular nucleophiles. The com-
mon intermediate formed in the case of alkyne substrates is alke-
nylgold. Although Au is the most electronegative metal in Pauling’s
scale (2.54) [11], the Au–C(sp2) bond has been shown to be
nucleophilic and can participate in C–C bond formation processes
[12–18]. While the nature of the C–C bond formation is to be estab-
lished [19], the reactivity does provide a new dimension for
Au-catalyzed reactions of alkynes and warrants more studies. We
have recently developed several versatile synthetic methods taking
advantage of the nucleophilicity of alkenylgolds [14–16]. In contin-
uation of our interest in this area, herein we report an unusual
Au-catalyzed dimerization of benzoxazol-2-yloxy enynes, where
two new C–C single bonds are formed involving the reaction of
nucleophilic Au–C(sp2) bonds.
2. Results and discussion
Our initial design to explore the nucleophilicity of Au–C(sp2)
bonds was shown in Scheme 1. We surmise that the imidoyloxy
group in homopropargylic imidate 1 can migrate upon Au activa-
* Corresponding author. Tel.: +1 775 784 6688.
E-mail address: lzhang@unr.edu (L. Zhang).
0022-328X/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2008.09.011

X. Huang, L. Zhang / Journal of Organometallic Chemistry 694 (2009) 520–523
521
O
NR
R
R
O
N
O
N
3
2
4
[Au]
1
[Au]
Z
[Au]
Y
B
1
A
O
NR
[Au]
O
NR
[Au]
Z
Z
Y
Y
Fig. 1. ORTEP representation of cyclooctadiene 6.
2
C
Scheme 1. Exploring the nucleophilicity of Au–C(sp2) bonds.
Various reaction conditions as well as Au catalysts were exam-
ined to improve the overall yield and improve the diastereoselec-
tivity. Some of the results were shown in Table 1. While the
yield of this reaction could not be improved substantially by
changing reaction temperatures (entries 1–3) and solvents (entries
4–6) as well as catalysts (entries 7–10), noteworthy are that Au(I)
complex Ph3PAuNTf2 resulted in the opposite diastereoselectivity
and that PtCl2 did not catalyze this reaction.
Our attempts to expand the scope of this chemistry were ham-
pered by the unstable nature of benzoxzaol-2-yloxy enynes. Most
substrates studied were prone to allylic rearrangement during
either their preparations or their reactions with Au catalysts, lead-
ing to the formation of undesired carbamates. One exception is
enyne 8 prepared from 2-iodocyclohept-2-enone. Reaction of 8 in
the presence of Au(III) complex 5 afforded an inseparable mixture
of cyclooctadiene diastereomers 9 (meso-isomer:rac-isomer = 5:1)
in 53% yield (Eq. (2)). The structures of 9 were deduced by compar-
ing the NMR spectra with those of 6 and 7
Scheme 2. Preparation of benzoxzaol-2-yloxy enyne 4.
rather simple, (b) their 13C NMR had the same number of signals as
4, and (c) their molecular weights revealed by ESI+ doubled that of
4. As a result, we reasoned that these products must be symmetric
dimers of 4, and assigned 1,5-cyclooctadiene structures to both of
them with one of center symmetry (i.e., the meso-isomer 6, Eq. (1))
and the other of C2 symmetry (i.e., rac-isomer 7, Eq. (1)). Fortu-
nately, the major product was crystalline, and its single crystal
X-ray crystallography (Fig. 1) indeed verified that it possesses a
1,5-cyclooctadiene core. Moreover, it was the meso-isomer 6
H
O
N
N
Cl Au
Cl
5
O
N
O
O
O
O
5 mol %
(2)
O
N
O
ð2Þ
ClCH2CH2Cl
rt, 1 h
H
53%
8
9
meso : rac = 5 : 1
O
N
H
5
In summary, an unusual Au-catalyzed dimerization of ben-
zoxazol-2-yloxy enynes was discovered. 1,5-Cyclooctadienes were
formed in fair yields as mixtures of meso- and rac-isomers.
Although the scope was limited, this unprecedented reaction re-
vealed an unknown aspect of Au chemistry. While the formation
of the two C–C single bonds can be readily explained by invoking
the nucleophilicity of alkenylgold species, substantial attractive
interaction between two molecules of the Au-bound dipolar inter-
mediates seems necessary considering their low concentrations in
the reactions. This interaction may be general to Au-catalyzed
reactions, and understanding of its nature will be of significance
for advancing Au catalysis.
H
Cl Au
Cl
O
N
O
N
O
N
O
5 mol %
O
O
+
O
(1)
O
ClCH2CH2Cl
rt, 10 h
O
N
O
N
O
H
40%
H
4.2
6
:
1
7
4
ð1Þ
This unprecedented dimerization of 4 is rather surprising, espe-
cially considering the formation of the 8-membered ring. Notwith-
standing, the formation of 6 and 7 can be explained by invoking
the formation of a Au-containing all-carbon 1,4-dipole of type B.
Hence, as shown in Scheme 3, Au(III)-catalyzed migration of the
benzoxazol-2-yloxy group leads to the formation of Au-containing
1,4-dipole D. The facile dimerization of D must be assisted by some
type of bimolecular association as reactions of D with dipolarophiles
were not observed. Although much study is warranted to under-
stand the nature of this association, we surmise that there may be
significant Au–Au interaction [27] between two molecules of dipole
D, thus facilitating their union. Both new C–C bonds should then be
formed via nucleophilic attack of the Au–C(sp2) bonds toward the
allylic cations [17], forming diastereoisomers 6 and 7.
3. Experimental
3.1. Au-catalyzed dimerization of 4
To a solution of benzoxazol-2-yloxy enyne 4 (58 mg, 0.24 mmol,
1 equiv.) in 4 mL of anhydrous 1,2-dichloroethane was added
dichloro(pyridine-2-carboxylato)gold(III) (4.7 mg, 0.012 mmol,
0.05 equiv.). The resulting mixture was stirred at 60 °C for 1 h.
The solvent was evaporated, and the residue was eluded through

522
X. Huang, L. Zhang / Journal of Organometallic Chemistry 694 (2009) 520–523
Scheme 3. Proposed mechanism for 1,5-cyclooctadiene formation.
Table 1
Au-catalyzed dimerization of 4 under various reaction conditions
Entry
Catalyst (5 mol%)
Solvent
Temperature (°C)
Time (h)
Yield (%)a
6:7b
1
2
3
4
5
6
7
8
9
10
5
5
5
5
5
5
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
THF
Toluene
MeCN
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
Toluene
40
60
80
60
60
60
60
60
60
60
3
1
1
1
1
1
1
1
1
1
42
56
33
55
52
17
46
52
52
–
4.5:1
4.2:1
3.9:1
4.5:1
6.4:1
2.5:1
3.8:1
1:2.1
3.9:1
–
AuCl3
Ph3PAuNTf2
PyAuCl3
PtCl2
a
Estimated by using diethyl phthalate as reference.
Determined by 1H NMR.
b
silica gel column using flash chromatography. meso-Dimer 6 was
isolated in 41% yield and the rac-dimer 7 was obtained in 9% yield.
Meso-Dimer 6: 1H NMR (400 MHz, CDCl3) d: 7.21–7.05 (m, 8H),
5.93 (d, 2H, J = 8.0 Hz), 5.83 (m, 2H), 3.58 (m, 2H), 2.20–2.14 (m,
4H), 2.07–2.00 (m, 2H), 1.75–1.58 (m, 6H). 13C NMR (125 MHz,
CDCl3) d: 153.2, 142.7, 133.3, 133.1, 132.2, 131.5, 130.4, 123.9,
122.5, 109.9, 109.6, 38.6, 29.0, 25.3, 20.4. IR (neat): 3352, 2936,
2254, 1771, 1601, 1482, 1379, 1045, 985; MS (ES+). Calculated
for [C30H26N2O4Na]+ 501.1; Found: 501.0. Racemic dimer 7: 1H
NMR (400 MHz, CDCl3) d: 7.22–7.20 (m, 2H), 7.12–7.04 (m, 4H),
6.84–6.81 (m, 1H), 5.79–5.77 (m, 2H), 5.75 (d, 2H, J = 8.8 Hz,),
4.20–4.13 (m, 2 H), 2.20–2.14 (m, 2H), 2.07–2.01 (m, 4H), 1.82–
1.62 (m, 6H). 13C NMR (125 MHz, CDCl3) d: 153.6, 142.5, 133.6,
132.4, 131.9, 131.7, 131.1, 123.9, 122.5, 109.8, 109.7, 36.5, 29.9,
25.4, 19.4. IR (neat): 2964, 2869, 2358, 1733, 1683, 1593, 1506,
1464, 1362, 1267, 910; MS (ES+). Calculated for [C30H26N2O4Na]+
501.1; Found: 501.0.
data_request/cif. Supplementary data associated with this article
can be found, in the online version, at doi:10.1016/
j.jorganchem.2008.09.011.
References
[1] A.S.K. Hashmi, Chem. Rev. 107 (2007) 3180–3211.
[2] A. Furstner, P.W. Davis, Angew. Chem., Int. Ed. 46 (2007) 3410–3449.
[3] E. Jimenez-Nunez, A.M. Echavarren, Chem. Commun. (2007) 333–346.
[4] N. Bongers, N. Krause, Angew. Chem., Int. Ed. 47 (2008) 2178–2181.
[5] D.J. Gorin, F.D. Toste, Nature 446 (2007) 395–403.
[6] N. Marion, S.P. Nolan, Angew. Chem., Int. Ed. 46 (2007) 2750–2752.
[7] S.M. Ma, S.C. Yu, Z.H. Gu, Angew. Chem., Int. Ed. 45 (2006) 200–203.
[8] N.T. Patil, Y. Yamamoto, ARKIVOC (v), 2007, pp. 6–19.
[9] L. Zhang, J. Sun, S.A. Kozmin, Adv. Synth. Catal. 348 (2006) 2271–2296.
[10] R.A. Widenhoefer, X.Q. Han, Eur. J. Org. Chem. (2006) 4555–4563.
[11] L. Pauling, The Nature of the Chemical Bond and the Structure of Molecules
and Crystals: An Introduction to Modern Structural Chemistry, 3rd ed., Cornell
University Press, Ithaca, NY, 1960.
[12] Z. Shi, C. He, J. Am. Chem. Soc. 126 (2004) 13596–13597.
[13] Z. Shi, C. He, J. Org. Chem. 69 (2004) 3669–3671.
[14] L. Zhang, J. Am. Chem. Soc. 127 (2005) 16804–16805.
Acknowledgments
[15] S. Wang, L. Zhang, J. Am. Chem. Soc. 128 (2006) 8414–8415.
[16] S. Wang, L. Zhang, J. Am. Chem. Soc. 128 (2006) 14274–14275.
[17] P. Dube, F.D. Toste, J. Am. Chem. Soc. 128 (2006) 12062–12063.
[18] L. Wei, C.J. Li, J. Am. Chem. Soc. 125 (2003) 9584–9585.
[19] (a) Addition of electrophiles to the C–C double bond of alkenygolds followed
by facile elimination of Au can account for their nucleophilicity. For such
proposed mechanisms, see: I. Nakamura, T. Sato, Y. Yamamoto, Angew. Chem.,
Int. Ed. 45 (2006) 4473–4475;
(b) E. Jimenez-Nunez, C.K. Claverie, C. Nieto-Oberhuber, A.M. Echavarren,
Angew. Chem., Int. Ed. 45 (2006) 5452–5455.
[20] For a previous study of Au-catalyzed imidate cyclization, see: A.S.K. Hashmi,
M. Rudolph, S. Schymura, J. Visus, W. Frey, Eur. J. Org. Chem. 71 (2006) 4905–
4909.
Generous financial supports from ACS PRF (43905-G1), ORAU
and Merck are appreciated. The acquisition of an NMR spectrome-
ter and upgrade of an existing NMR spectrometer is funded by NSF
CHE-0521191 and the X-ray diffractometer purchase was sup-
ported by NSF Grant CHE-0226402.
Appendix A. Supplementary material
CCDC 644034 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
[21] G. Zhang, X. Huang, G. Li, L. Zhang, J. Am. Chem. Soc. 130 (2008) 1814–1815.
[22] G. Zhang, L. Zhang, J. Am. Chem. Soc. 130 (2008) 12598–12599.
[23] M.E. Krafft, J.W. Cran, Synlett (2005) 1263–1266.

X. Huang, L. Zhang / Journal of Organometallic Chemistry 694 (2009) 520–523
523
[24] Trichloroacetimidates are stable and can be generated readily. However, we
were concerned that the NH group might release proton during Au catalysis,
which could protonate the Au–C(sp2) bond. For a reported case, see: J.-E. Kang,
H.-B. Kim, J.-W. Lee, S. Shin, Org. Lett. 8 (2006) 3537–3540.
[25] Au-catalyzed cyclization of the nitrogen of benzoxazole rings to alkynes has
been reported before. For reference, see: R. Lok, R.E. Leone, A.J. Williams, J. Org.
Chem. 61 (1996) 3289–3297.
[26] A.S.K. Hashmi, J.P. Weyrauch, M. Rudolph, E. Kurpejovic, Angew. Chem., Int. Ed.
43 (2004) 6545–6547.
[27] For the original report about aurophilicity, see: F. Scherbaum, A. Grohmann, B.
Huber, C. Krueger, H. Schmidbaur, Angew. Chem., Int. Ed. 27 (1988) 1544–
1546.