Experimental and theoretical investigation into the gold-catalyzed reactivity of cyclopropenylmethyl acetates

Article abstract of DOI:10.1021/ol101862u

Cyclopropenylmethyl acetates have been shown to undergo rapid and stereoselective gold catalyzed rearrangement to Z-acetoxydienes in high yield. DFT calculations have shown that while several reaction pathways can be envisaged only a single, ring-opening one operates.

Full text of DOI:10.1021/ol101862u

ORGANIC
LETTERS
2010
Vol. 12, No. 21
4768-4771
Experimental and Theoretical
Investigation into the Gold-Catalyzed
Reactivity of Cyclopropenylmethyl
Acetates
Elaine Seraya,† Eric Slack,† Alireza Ariafard,*,‡,§ Brian F. Yates,‡ and
Christopher J. T. Hyland*,†,‡
Department of Chemistry and Biochemistry, California State UniVersity, Fullerton,
California 92831, United States, School of Chemistry, UniVersity of Tasmania,
PriVate Bag 75, Hobart TAS 7001, Australia, and Department of Chemistry, Faculty of
Science, Central Tehran Branch, Islamic Azad UniVersity, Shahrak Gharb, Tehran, Iran
chyland@fullerton.edu; alireza.ariafard@utas.edu.au
Received August 9, 2010
ABSTRACT
Cyclopropenylmethyl acetates have been shown to undergo rapid and stereoselective gold catalyzed rearrangement to Z-acetoxydienes in
high yield. DFT calculations have shown that while several reaction pathways can be envisaged only a single, ring-opening one operates.
The diverse reactivity of propargyl acetates in the presence of
gold catalysts is currently being investigated by several groups.1
For example, propargyl acetates 1 can undergo gold-catalyzed
1,3- or 1,2-acyl migrations via 2 and 3 to form 4 and 5,
respectively. Intermediates 4 and 5 are poised to react further
giving a diverse range of products resulting from allene
activation and carbene-type reactivity, respectively (Figure 1).2
In this context, we decided that cyclopropenylmethyl acetates,
which are highly strained homologues of propargyl esters,
† California State University.
‡ University of Tasmania.
§ Islamic Azad University.
Figure 1. Propargyl acetate and cyclopropenylmethyl acetate
activation by gold catalysts.
(1) For reviews on gold-catalyzed reactions of propargyl acetates, see:
(a) Marion, N. P.; Nolan, S. P. Angew. Chem., Int. Ed. 2007, 46, 2750. (b)
Correa, A.; Marion, N.; Fensterbank, L.; Malacria, M.; Nolan, S. P.; Cavallo,
L. Angew. Chem., Int. Ed. 2008, 47, 718.
should also lead to interesting reactivity upon activation by gold
salts.3 While cyclopropenes with their π-rich double bond and
high strain character would appear to be ideal substrates for
activation by gold, there has been relatively little investigation
of this aspect of their chemistry. To date, Lee and co-workers
have described the gold-catalyzed solvolysis of simple alkyl
(2) For examples of 1,2- and 1,3-shifts of propargyl esters, see refs 3
and 4 within review.1a For selected more recent examples of 1,2-shifts,
see: (a) Blanc, A.; Alix, A.; Weibel, J. M.; Pale, P. Eur. J. Org. Chem.
2010, 9, 1644. (b) Huang, X. G.; de Haro, T.; Nevado, C. Chem.sEur. J.
2009, 24, 5904. For selected recent examples of 1,3-shifts, see: (c)
Garayalde, D.; Gomez-Bengoa, E.; Huang, X. G.; Goeke, A.; Nevado, C.
J. Am. Chem. Soc. 2010, 132, 4720. (d) Yu, M.; Zhang, G. Z.; Zhang, L. M.
Tetrahedron 2009, 65, 1849.
10.1021/ol101862u  2010 American Chemical Society
Published on Web 09/28/2010

cyclopropenes,4a while both Shi and Zhu4b as well as Wang
and co-workers4c have demonstrated the cycloisomerization of
cyclopropenes to afford indene derivatives. In this paper, we
report our combined experimental and theoretical investigation
into the reactivity of cyclopropenylmethyl acetates 6. Their
extremely facile transformation into Z-acetoxy dienes by the
action of AuPPh3NTf2 is demonstrated, and a rationale for both
the mechanism and stereoselectivity of this reaction is provided.
We began our experimental investigations by preparing
the required cyclopropenylmethyl acetates from tribromocy-
clopropanes using the method of Baird et al.,5 followed by
acetylation of the resulting alcohols. Nitrobenzaldehyde-
derived cyclopropene 8a was chosen as our first substrate
as its crystalline nature would enable product identification
by X-ray analysis if necessary (Table 1). Upon exposure of
examples of thermally induced cyclopropene-carbene rear-
rangements which provide mixtures of dienes and other prod-
ucts.8 It is also of note that Zhang and co-workers have reported
a gold-catalyzed rearrangement of propargyl acetates to acetoxy
dienes with high Z-selectivity.9 Given our promising initial
result, we began a catalyst screen to identify optimum conditions
for obtaining 9a in high yield and high Z-selectivity, the results
of which are summarized in Table 1. It was determined that
AuPPh3NTf2 was the optimum catalyst for the reaction and that
lowering the temperature to -50 °C provided optimum
selectivity for the Z-diene. An NMR experiment revealed that
further lowering the temperature to -78 °C slowed the reaction
but did not increase the Z-selectivity of the reaction.
With selective diene-forming reaction in hand, we set
about exploring the substrate scope of the rearrangement
Table 1. Discovery and Optimization of Reaction Conditions for
Diene Formation
Table 2. Substrate Scope for the Diene-Forming Reaction
entry
1
catalysta
conditionsb
% yield 9a (Z:E)c
AuPPh3Cl/AgSbF6 DCM, rt, 20 min
66 (4:1)
0
2d AuPPh3Cl/AgBF4 DCM, rt, 12 h
3d AuCl
DCM, rt, 12 h
7 (4.5:1)
24 (3.8:1)
23 (3.6:1)
25 (4:1)
28 (3.7:1)
99 (8:1)
99 (13:1)f
4
5
6
7
8
9
AuPtBu3Cl/AgSbF6 DCM, rt, 30 min
[(Ph3PAu)3O]BF4
IPrAuCl
DCM, rt, 12 h
DCM, rt, 30 min
DCM, rt, 12 h
DCM, rt, 30 min
DCM, -50 °C, 5 min
Au(III)e
PPh3PAuNTf2
PPh3PAuNTf2
a All reactions run with 5 mol % of catalyst unless otherwise stated.
b Reactions run at 0.144 M for entries 1-9. c NMR yields using MeNO2 as
an internal standard. d 15% and 26% of starting material remaining for entries
2 and 3, respectively. e Dichloro(2-pyridinecarboxylato)gold. f Isolated yield.
8a to the AuPPh3Cl/AgSbF6 precatalyst system, we were
delighted to find that rearrangement to the Z-acetoxy diene 9a
occurred in 66% yield with a 4:1 Z:E selectivity (Table 1, entry
1). The stereochemistry of the major Z isomer was confirmed
unambiguously by X-ray crystallography.6 In the context of
diene-forming reactions from cyclopropenes, early work by
Mu¨ller and co-workers reports a single example of a sym-
metrical cyclopropene ethylcarboxylate forming a diene in the
presence of a Rh(III) catalyst.7 There are also several early
(3) For recent reviews on cyclopropene synthesis and reactivity, see:
(a) Rubin, M.; Rubina, M.; Gevorgyan, V. Chem. ReV. 2007, 107, 3117.
(b) Marek, I.; Simaan, S.; Masarwa, A. Angew. Chem., Int. Ed. 2007, 46,
7364. For a specific example of the reactivity of cyclopropenylmethyl
acetates, see: (c) Simaan, S.; Masarwa, A.; Zohar, E.; Stanger, A.; Bertus,
P.; Marek, I. Chem.sEur. J. 2009, 15, 8449.
(4) (a) Bauer, J. T.; Hadfield, J. T.; Lee, A.-L. Chem. Commun. 2008,
6405. (b) Zhu, Z. B.; Shi, M. Chem.sEur. J. 2008, 14, 10219. (c) Li, C. K.;
Zeng, T.; Wang, J. B. Tetrahedron Lett. 2009, 50, 2956.
(5) M. S. Baird, M. S.; Hussain, H. H.; W. Nethercott, W. J. Chem.
Soc., Perkin Trans. 1 1986, 1, 1845.
(Table 2). We were pleased to find that a wide selection of
aryl-derived cyclopropenylmethyl acetates underwent very
(6) James Qiang Zhang and Katherine Kantardjieff of CmolS, California
State University, Fullerton are gratefully acknowleged for structure deter-
mination.
(7) Mu¨ller, P.; Pautex, N.; Doyle, M. P.; Bagheri, V. HelV. Chim. Acta
1990, 73, 1233.
(8) Baird, M. S. Chem. ReV. 2003, 103, 1271.
(9) Li, G.; Zhang, G.; Zhang, L. J. Am. Chem. Soc. 2008, 130, 3740.
Org. Lett., Vol. 12, No. 21, 2010
4769

selective gold-catalyzed rearrangement to (Z)-2-acyloxy-1,3-
dienes 9a-g. Notably, 9e bearing an o-bromobenzyl group
rearranged with an impressive 41:1 Z:E selectivity. Also of
interest was the reduced Z:E selectivity observed for the dodecyl
aldehyde derived 9g. It should also be noted that while electron-
rich 9f underwent rapid rearrangement the resulting diene
decomposed before purification could be carried out.
The diene-forming reaction is fascinating in terms of both
the mechanism and the observed stereoselectivity, especially
when compared to the gold-catalyzed reactions of propargyl
esters 1. A number of mechanistic possibilities can be
envisaged following activation of the cyclopropene double
bond by gold. Similarly to propargyl esters 1, both 1,2- and
1,3-migration to form 10 and 13, respectively, can be
envisaged for cyclopropene 6 (Figure 2; pathways a and b).
To address these questions, we turned our attention to
computational studies, the results of which are now discussed.
In our DFT calculations, we used the model catalyst
[AuPMe3]+ in conjunction with reactants bearing R ) phenyl
and ethyl to model the aryl and alkyl substrates, respectively.
Our theoretical studies showed that all four pathways are
thermodynamically very favorable; however, they all differ
significantly in terms of kinetics. On the basis of our calculations
with the substrate R ) phenyl, the highest Gibbs free energy
points for pathways a, b, c, and d are 17.3, 17.0, 11.8, and 37.5
kcal mol-1, respectively. For R ) ethyl, the corresponding
Gibbs free energy points for pathways a, b, c, and d are 17.8,
22.9, 11.7, and 35.1 kcal mol-1, respectively. Therefore, the
calculations show that regardless of the identity of the R group
the ring-opening pathway c is always kinetically favored. As
such, the detailed mechanism of pathway c for R ) phenyl
and ethyl is illustrated in Figure 3, and the other pathways are
provided in the Supporting Information.
The preference for this ring-opening mechanism can be
explained based on the associated relief of ring strain upon
Figure 2. Potential pathways for reaction of gold-coordinated 6.
Given that diene 9 is the only product observed, pathway a
toward methylenecyclopropane 11 cannot be operating.
However, pathway b can lead to the observed diene product
9 via 1,2-shift to bicyclic 13 followed by ring opening. On
the other hand, Lee and co-workers proposed a ring-opening
mechanism to account for the observed allyl ether products
in their solvolysis of cyclopropenes.4a In addition, a recent
mechanistic study by Fu¨rstner and co-workers has shown
that cyclopropenone acetals undergo ring opening in the
presence of gold catalysts.10 Given these reports, we designed
two alternative pathways, c and d, that both proceed via initial
formation of gold vinyl carbenoid species 12. Attack of the
pendant acetate can then occur at carbon a to give the observed
diene 9 or at carbon c to give allene 14. These mechanistic
possibilities pose four important questions: (1) Does the diene
form via the ring-opening-migration pathway c or the
migration-ring-opening pathway b. (2) What is the reason that
pathways a and d are not operating. (3) What is the origin of
the observed high Z-selectivity for substrates 9a-f with R )
aryl and the negligible selectivity for 9g with R ) dodecyl.
Finally, (4) does the replacement of an aryl group with an alkyl
group affect the preferred pathway followed?
Figure 3. Energy profiles calculated for pathway c of the gold-
catalyzed rearrangement of cyclopropenylmethyl acetates. The
relative free energies (and electronic energies in parentheses) are
given in kcal mol-1. The values in bold refer to R ) phenyl, and
the italicized values refer to R ) ethyl.
(10) Seidel, G.; Mynott, R.; Fu¨rstner, A. Angew. Chem., Int. Ed. 2009,
48, 2510–2513.
4770
Org. Lett., Vol. 12, No. 21, 2010

formation of 2_R11 (Figure 3). Although pathway d also
proceeds via 2_R, this pathway is not followed because
attack of the pendant acetate on carbon c (Figure 2) requires
a higher deformation energy in the transition structure resulting
in a raised energy barrier. This attack is disfavored because of
the greater distance of the acetate from carbon c. For example,
in 2_R (R ) phenyl) the sp2 oxygen is 5.667 Å away from
carbon c but only 3.895 Å away from carbon a. In the favored
pathway c, we considered two conformations R and R′ of the
starting cyclopropene to be reactive toward ring opening. In
conformation 0_R′, the R group is pointing toward the gem-
dimethyl group, whereas in 0_R it is pointing away from it.
These two conformations undergo initial coordination to the
gold to yield adducts 1_R and 1′_R, which can both lead to
the ring-opened 2_R intermediate. It is of interest to note that
the slightly less stable conformer 0_R has a lower activation
barrier toward ring opening (see top of Figure 3). Following
ring opening, the pendant acetate can undergo 1,2-transfer in
two steps. Attack of the acetate on carbon a (see 12, Figure 2)
occurs first to provide the five-membered ring intermediates
3_R and 3′_R, and then breaking of these five-membered rings
takes place to give the products 4_R and 4′_R (bottom of Figure
3). As illustrated in Figure 1, starting from 2_R there are two
possibilities leading to the Z and E isomers, respectively. Our
calculations show that from 2_R the energy barrier for the
formation of the Z diene 4′_R is significantly lower than that
of the E-diene 4_R. The preference for the pathway leading to
formation of 4′_R can be explained by a steric argument. In
the pathway leading to the formation of 4_R, the R group is
pointing toward the methylbut-2-ene fragment resulting in an
unfavorable steric repulsion; this steric repulsion is absent in
the pathway leading to the formation of 4′_R. It can therefore
be seen that the stereoselectivity of the reaction is controlled
by a steric interaction between the R group and the methylbut-
2-ene fragment (Figure 4). This fits in with the experimental
Z-selectivity (dienes 9b and 9e, Table 2). In both pathways
shown at the bottom of Figure 1, the energy barrier for the
breaking of the five-membered ring (3TS_R and 3TS′_R) is
greater than for its formation (2TS_R and 2TS′_R). For both
R ) phenyl and ethyl, 3TS_R is higher in energy than 3TS′_R,
but the energy difference for R ) ethyl (1.6 kcal mol-1) is
significantly smaller than for R ) phenyl (5.7 kcal mol-1),
resulting in the low Z-selectivity observed for R ) alkyl (see
9g) and the high Z-selectivity observed for R ) aryl (see 9a-e).
The lowered difference in energy between 3TS_R and 3TS′_R
for R ) ethyl is due to the reduced steric effect of the alkyl
group compared to an aryl group. The akyl group has the ability
to adopt a conformation where two hydrogens are pointing
toward the 2-methylbut-2-ene fragment in 3TS_R, resulting in
a less congested and a lower-energy transition state compared
to that of the phenyl group (see Figure S4, Supporting
Information). In conclusion, we have developed an efficient and
stereoselective synthesis of Z-acetoxydienes 9a-g. On the basis
of DFT calculations, we have been able to propose a detailed
mechanism for the formation of these dienes. These calculations
show that ring opening, followed by intramolecular 1,2-acetate
transfer, is the most favorable pathway and that the ring opening
is rate determining.
The mechanistic divergence of cyclopropenylmethyl acetates
6 from propargyl acetates 1 is an important aspect of the
chemistry uncovered here. In Nolan’s elegant computational
study,1b he demonstrated that the gold vinyl carbenoid species
5 and the gold allene species 4 are in rapid equilibrium and
that the exact product obtained is dependent upon a variety of
factors, including precise substrate structure and the nature of the
ligand employed. It is significant that in the case of cyclopro-
penylmethyl acetate 6 reactivity is guided unambiguously
toward a ring-opening pathway due to the cyclic nature of the
starting material. Cyclopropenes 6 also differ from propargyl
acetates in that they afford gold vinyl carbenoid 12, which is
an isomer of gold vinyl carbenoid 5. We anticipate that the
ability to prepare this alternative gold vinyl carbenoid, along
with the mechanistic detail presented here, will stimulate further
research into the development of new gold-catalyzed reactions
of cyclopropenylmethyl acetates. Research is currently under-
way to further develop the synthetic potential of these substrates
and to identify cyclopropenes that will react via the alternative
pathways outlined in Figure 2.
Acknowledgment. This work was supported by an award
from the Research Corporation (CC6929). Financial support
by California State University, Fullerton, is also gratefully
acknowledged. The acquisition of an NMR spectrometer was
funded by NSF CHE-0521665. We also thank the Australian
Research Council for funding and the National Computational
Infrastructure (NCI) and the Tasmanian Partnership for Ad-
vanced Computing (TPAC) for provision of computing.
Figure 4. Optimized geometries for 3TS′_R and 3TS_R (R )
phenyl).
Supporting Information Available: Full computational
details, experimental procedures, and full spectroscopic data
for all new compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
results where the more sterically demanding substrates with R
) o-chlorophenyl and R ) o-bromophenyl result in the highest
(11) 2_R is the reactive conformation of structure 12 in Figure 2, and
the IRC calculations show that 1TS_R is directly connected to 2_R.
OL101862U
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