Gold(I)-catalysed tandem cyclisation of propargyl acetals and vinyl esters

Article abstract of DOI:10.1002/ejoc.201301674

The results of our previous comparative study of chemoselective gold(I)-catalysed alkene cycloadditions of propargyl substrates demonstrated that propargyl acetals react by different cyclisation pathways from the corresponding esters, and that they also have significantly higher reactivities. To increase understanding of the chemistry of propargyl acetals and to explore the possibilities of generating new compounds through gold(I)-catalysed reactions, a range of reactions of propargyl acetals with vinyl esters have been carried out. A new type of cyclopropyl-cyclopentenyl products, (1,3-dimethoxy-4,5-diphenylcyclopent-2-en-1-yl)-cyclopropyl ester derivatives, was obtained. A plausible mechanism, including sequential [1+2] and [2+3] cycloadditions, is proposed for these highly regio- and stereoselective gold(I)-catalysed reactions. The cyclopentenylation took place stereoselectively, whereas cis/trans mixtures of diastereoisomers were formed in the cyclopropanation step, with the selectivity being controlled by the bulkier vinylic substituent. The tandem reaction allows the construction of polysubstituted and highly functionalised bicyclic compounds. Copyright

Full text of DOI:10.1002/ejoc.201301674

FULL PAPER
DOI: 10.1002/ejoc.201301674
Gold(I)-Catalysed Tandem Cyclisation of Propargyl Acetals and Vinyl Esters
Huey-San Melanie Siah,[a] Maya Kaur,[a] Naseem Iqbal,[a] and Anne Fiksdahl*[a]
Keywords: Alkynes / Gold / Homogeneous catalysis / Tandem reactions / Vinylic compounds / Cyclization
The results of our previous comparative study of chemoselec-
tive gold(I)-catalysed alkene cycloadditions of propargyl sub-
strates demonstrated that propargyl acetals react by different
cyclisation pathways from the corresponding esters, and that
they also have significantly higher reactivities. To increase
understanding of the chemistry of propargyl acetals and to
explore the possibilities of generating new compounds
through gold(I)-catalysed reactions, a range of reactions of
propargyl acetals with vinyl esters have been carried out. A
new type of cyclopropyl–cyclopentenyl products, (1,3-di-
methoxy-4,5-diphenylcyclopent-2-en-1-yl)-cyclopropyl ester
derivatives, was obtained. A plausible mechanism, including
sequential [1+2] and [2+3] cycloadditions, is proposed for
these highly regio- and stereoselective gold(I)-catalysed re-
actions. The cyclopentenylation took place stereoselectively,
whereas cis/trans mixtures of diastereoisomers were formed
in the cyclopropanation step, with the selectivity being con-
trolled by the bulkier vinylic substituent. The tandem reac-
tion allows the construction of polysubstituted and highly
functionalised bicyclic compounds.
esters with vinyl esters or amides (Scheme 1a, product
III).[8] Changing from propargylic esters to acetals, the reac-
tion pathway switches. The gold(I)-catalysed cyclisation re-
actions of propargyl acetals with vinyl amides or vinyl
ethers are characterised by two important features. Firstly,
in contrast to the usual olefin cyclopropanation that nor-
mally takes place with propargyl esters, an atypical cyclo-
pentenylation by a [2+3] cycloaddition mechanism is the
favoured reaction pathway for the corresponding acetals,[9]
leading to trans-configured cyclopentenyl products
(Scheme 1b, product IV). This reaction proceeds by a
“C-3–C-1” reaction sequence, due to the presence of an alk-
oxy group in adduct IIЈ, which activates it for C-1 cycli-
sation. Secondly, propargyl acetals show a significantly
higher reactivity than the corresponding esters,[9,10] which
is consistent with the assumption that the alkoxy substitu-
ent may activate the intermediate gold–propargyl-acetal
complex II. Our recent studies have shown that propargyl
acetals also undergo a gold-catalysed [2+5] cycloaddition
with benzaldimines to give benz[c]azepine products
(Scheme 1c, compound V).[10]
However, by replacing the vinyl amides or vinyl ethers
(Scheme 1, b) with vinyl esters, the reaction outcome was
altered. Propargyl acetals and vinyl esters were found to
undergo a gold(I)-catalysed tandem cyclisation reaction in-
volving two propargyl–gold units II, generated from pro-
pargyl acetals, to give rise to cyclopropyl–cyclopentenyl
products VI (Scheme 1, d).
We wanted to further investigate the ability of the highly
reactive gold(I) vinylcarbenoid complexes II to promote
chemoselective cyclisations, and we chose to study the po-
Introduction
Gold(I) complexes are known to be efficient catalysts for
the activation of C–C multiple bonds towards nucleophilic
attack.[1–4] Propargylic esters and acetals have been shown
to undergo triple-bond activation, followed by, respectively,
1,2-acyloxy and 1,5-alkoxy migrations. Subsequent nucleo-
philic attack generates a variety of complex small molecules
with one or more chiral centres.[5–7] The structures of the
products depend on the nature of both the propargyl moi-
ety and the nucleophile.
The Fiksdahl group has previously reported a compara-
tive study of the reactivity of chemoselective gold(I)-cata-
lysed cycloadditions of propargyl esters and acetals with
vinyl derivatives (Scheme 1a and b), and has shown how
the regioselectivity of the cycloadditions is controlled by the
electronic nature of the substrates.[8,9] Such propargyl deriv-
atives are known to undergo gold(I)-catalysed migration–
fragmentations to give gold carbenoid intermediates (I, II),
which can be trapped with different reagents, typically alk-
enes, to give adducts IЈ and IIЈ. We have studied such reac-
tions with olefins directly connected to a heteroatom.
Cyclopropanation by a [1+2] cycloaddition reaction
pathway is typical for the reactions of terminal propargyl
[a] Department of Chemistry, Norwegian University of Science
and Technology
Høgskoleringen 5, 7491 Trondheim, Norway
E-mail: anne.fiksdahl@chem.ntnu.no
http://www.ntnu.edu/employees/anne.fiksdahl
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301674.
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H.-S. M. Siah, M. Kaur, N. Iqbal, A. Fiksdahl
FULL PAPER
Scheme 1. Gold(I)-catalysed cycloaddition reactions of propargyl substrates.[8–10]
tential for propargyl acetals to give tandem products with Optimisation Studies
vinyl esters by a double cycloaddition process. In this paper,
we report the results of our studies on the new gold(I)-cata-
lysed tandem reaction.
Optimisation studies showed that substrates 2a and 3a
readily gave a 54% yield of products 4 after 15 min in the
presence of [Au{P(tBu)2(o-biphenyl)CH3CN}]SbF6 (5 mol-
%) in dichloromethane (Table 1, entry 1). These reaction
conditions were used in further studies, as they gave the
highest reactivity towards tandem cyclisation. The use of
acetonitrile as a solvent resulted in a lower yield, and re-
Results and Discussion
Introductory studies into the reaction of propargyl acetal quired a longer reaction time (48%, 60 min; Table 1, en-
2a and vinyl acetate (3a; 3 equiv. based on the propargyl try 2). Tetrahydrofuran seemed to undergo polymerisation,
substrate) in the presence of a gold(I) catalyst were carried so it was deemed to be an unsuitable solvent for these reac-
out under reaction conditions previously used for propargyl tions (Table 1, entry 3). A similar gold(I) catalytic complex
acetal cycloadditions.[9] Structural studies (NMR spec- lacking the acetonitrile ligand gave lower yields (31%;
troscopy) showed that the tandem cyclisation product could Table 1, entry 4). As previously observed,[9] no reaction
be identified as 2-(1,3-dimethoxy-4,5-diphenylcyclopent-2- took place when [Au{P(tBu)2(o-biphenyl)}]Cl was used,
enyl)cyclopropyl acetate, formed as a mixture of dia- and it was important to generate the active gold(I) species
stereomers (cis-/trans-4a).
by exchange of the chloride counterion with SbF6– (Table 1,
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Gold(I)-Catalysed Tandem Cyclisation
Table 1. Optimisation studies of gold(I)-catalysed tandem cyclisation reactions.[a]
Entry
Gold catalyst
Solvent (time)
Yield [%] (cis/trans)
1
2
3
4
5
6
7
8
{Au[P(tBu)2(o-biphenyl)CH3CN]}SbF6
{Au[P(tBu)2(o-biphenyl)CH3CN]}SbF6
{Au[P(tBu)2(o-biphenyl)CH3CN]}SbF6
{Au[P(tBu)2(o-biphenyl)]}Cl + AgSbF6
{Au[P(tBu)2(o-biphenyl)]}Cl
Au(PPh3)Cl + AgSbF6
CH2Cl2 (15 min)
CH3CN (60 min)
THF (60 min)
CH2Cl2 (15 min)
CH2Cl2 (19 h)
CH2Cl2 (15 min)
CH2Cl2 (15 min)
CH2Cl2 (19 h)
54 (60:40)
48 (60:40)
n.d.[b]
31 (65:35)
n.d.
n.d.[c]
AuCl3
PicAuCl2
n.d.[c]
1a/2a; 3:2[c]
[a] The reactions were performed with 2a (1 equiv.) and 3a (3 equiv.) in solvent (approx. c = 90 mm) together with 5 mol-% gold catalyst
at room temp. [b] Target molecules not detected (n.d.); polymerisation of THF at room temp.; no conversion at –78 °C. [c] Target mole-
cules not detected (n.d.); hydrolysis into 1-phenylprop-2-yn-1-ol 1a was observed by GC.
entry 5).
A triphenylphosphane-based gold(I) catalyst ucts formed in reactions of propargyl esters with vinyl esters
(Table 1, entry 6) and gold(III) salts (Table 1, entries 7 and or sulfonamides (Scheme 1, a).[8] The results of our previous
8) resulted in full or partial hydrolysis into to the propargyl studies indicate that propargyl acetals may be expected to
alcohol.
undergo [2+3] cycloadditions with vinylic substrates
(Scheme 1, b).[9] Nevertheless, we have also seen that the
electronic nature of the vinylic reactants connected to a het-
eroatom may affect the reactivity and alter the reaction
Proposed Mechanism
Based on our previous studies of regioselective cycload- pathway and the outcome of propargyl cycloaddition reac-
ditions of propargyl substrates,[8,9] the formation of tandem tions.[8–10] The unexpected cyclopropanation reaction that
product 4 is proposed to take place by a two-step reaction. was found to be the favoured pathway for the reaction of
The general mechanism is shown for propargyl acetal 2 and propargyl acetals and vinyl esters may be a result of the
vinyl ester 3 in Scheme 2.
presence of the electron-withdrawing ester moiety in adduct
Propargyl acetal 2 and vinyl ester 3 undergo an initial IIЈ (Scheme 2). This is in contrast to the situation with vin-
gold(I)-catalysed [1+2] cycloaddition reaction to give the ylic compounds attached to an electron-releasing nitrogen
cyclopropanation product (i.e., IIIЈ) by nucleophilic attack or oxygen atom, which would enable stabilisation of an am-
of the vinyl species on the gold carbenoid intermediate (i.e., monium or oxonium cation intermediate IIЈ (Scheme 1, b).
II). The observed cyclopropyl products correspond to prod- Hence, electron-deficient vinylic compounds such as vinyl
Scheme 2. Proposed mechanism for gold(I)-catalysed tandem cyclisation reaction of propargyl acetals and vinyl esters.
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H.-S. M. Siah, M. Kaur, N. Iqbal, A. Fiksdahl
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esters may reduce the electron-releasing effect of the vinylic high yields (39–77%; Table 2, entries 1, 2, 4, 5, 7, and 8)
alkoxy group[9] in adduct IIЈ. This would then decrease the were generally obtained at –40 to –78 °C. This clearly dem-
tendency for the alkoxy group to promote a C-1 cyclisation onstrates the ability of these highly reactive substrates to
that would result in pentaannulation. This electronic effect undergo tandem reactions. The corresponding tandem reac-
appears to make it more favourable for intermediate adduct tions with vinylsulfonamides were not as promising. With
IIЈ to undergo cyclopropyl ring formation.
vinyltosylate (vinyl-OTs), propargyl substrates 2a and 2c
In contrast to the cyclopropyl products III previously ob- gave two major products (as judged by TLC), but these
tained from propargyl esters (Scheme 1, a), product IIIЈ were unstable, and they decomposed during work-up. Only
contains an activated vinyl ether moiety. Thus, intermediate low yields (up to 15%) of the unstable cis tandem products
IIIЈ may give rise to the new tandem reaction pathway by a were obtained.
subsequent cycloaddition reaction with gold carbenoid in-
Aromatic propargyl acetals (2a–2d, up to 77% yields,
termediates II, generated from a second unit of propargyl Table 2, entries 1, 2, 5, 7, 8, 9, and 11) generally performed
acetal 2. However, in contrast to the “C-3–C-1” reaction better than alkyl propargyl acetal 2e (up to 15% yield,
sequence previously reported for the [2+3] cycloadditions Table 2, entries 14 and 15). This demonstrates that benzylic
of monosubstituted vinylic reactants (Scheme 1, b),[9] the stabilisation of the cationic gold intermediate is beneficial,
opposite regioselectivity (i.e., a “C-1–C-3” reaction order) but that it is not a requirement for the tandem cycload-
was observed, since the vinyl nucleophile (i.e., IIIЈ) attacks dition. Bulky dimethyl propargyl substrate 2f (Table 2, en-
at the electrophilic allylic C-1 position of the second gold try 16) failed to undergo the tandem cyclisation with vinyl
carbenoid complex (i.e., II) to give adduct IIЈЈЈ. This change acetate (3a), and only a minor compound (approx. 5%),
in regioselectivity may be due to the bulk of the 3-substi- which, by NMR spectroscopy, seemed to be cyclopropyl in-
tuted vinyl ether IIIЈ. A similar “C-1–C-3” reaction order termediate 3f, was obtained. The difference in reactivity ob-
has been reported for [2+3] cycloaddition reactions of non- served between dimethylpropargyl acetal 2f and mono-
terminal propargyl acetals connected to an electron-with- methyl substrate 2e (Table 2, entry 14) may be explained by
drawing group, with aldehydes.[4]
steric effects. Tandem cyclisations were also disfavoured by
The fact that a cyclopropyl intermediate IIIЈ (i.e., 3e) was increasing the bulk of the vinyl ester substrates, as the reac-
actually isolated from the reaction of the deactivated p- tivity dropped and the yields were reduced when further
nitrophenylpropargyl acetal 2d (see below; Table 2, en- substituents were introduced onto the vinyl moiety (Me/3c;
try 12) supports the proposed tandem mechanism.
Ph/3d; Table 2, entries 3, 6, 9, and 10).
Despite the formation of five stereogenic centres in prod-
The presence of a para substituent on the aromatic pro-
uct 4, only one pair of cis/trans cyclopropyl diastereomers pargyl acetals affected the reactivity and the outcome of the
could be observed (Table 1), as the cyclopentenyl ring was tandem reactions. Unsubstituted phenyl propargyl acetal 2a
formed in a diastereoselective 4,5-trans (Ph–Ph)/1,5-cis gave good yields of the respective tandem products 4 and 5
(OMe-Ph) /it>/trans-cyclopropanation[8] and stereoselective (65–69%; Table 2, entries 1 and 2) in reactions with vinyl
pentaannulation[9] reactions.
acetate (3a) and vinyl benzoate (3b) at –78 °C. Test reac-
The overall outcome of the reaction is therefore the for- tions with the bulkier, but analogous ethyl acetal,
mation of tandem products cis/trans-4 by two sequential PhCH(CCH)OCHMe(OEt), and vinyl benzoate (3b) indi-
cycloaddition reactions, involving two units of propargyl cated a slower reaction, but similar yields of the corre-
acetal 2 and one unit of vinyl ester 3.
sponding tandem product seemed to be formed.
The presence of an electron-donating group in the pro-
pargyl substrate, such as the methoxy functionality in 2b,
would make it less electrophilic, and so make the nucleo-
philic attack of the vinyl species on the gold carbenoid in-
termediates II in both steps of the tandem cyclisation less
Reactivity
The tandem transformation was further studied by mod- favourable (Scheme 2). Consistent with this hypothesis, we
ifying the substrates and the reaction conditions. The re- observed decreased yields of tandem products 6 and 7 (39–
sults from the reactions of propargyl acetals 2a–2e with vin- 49%; Table 2, entries 4 and 5) from p-OMe-phenylprop-
ylic esters 3a–3d in the presence of {Au[P(tBu)2(o-biphen- argyl acetal 2b and vinyl esters 3a and 3b. Furthermore, a
yl)CH3CN]}SbF6 in CH2Cl2 are presented in Table 2. The propargyl acetal dimer 17 was formed in the reactions car-
propargyl acetals gave the expected tandem cyclisation ried out at room temperature (Table 2, entries 4 and 5; foot-
products (i.e., 4–16), but the yields varied depending on the note [h]). Significant amounts of the dimer were formed
substituents on the propargyl acetal and the vinylic reac- (GLC, TLC), but it was unstable both during flash
tant. Additionally, the stability of the tandem products at chromatography and in deuterated solvents. Attempts to
room temperature appeared to vary, which could account prepare larger amounts of dimer 17 by separate dimeri-
for a reduction in the isolated yields. Temperature optimi- sation of propargyl acetal 2b resulted in the formation of
sation (room temp. to –78 °C) was carried out for each reac- only small amounts of 17 (Ͻ 5%), which could be used for
tion, as complex mixtures of products were most often ob- characterisation and structural elucidation. A possible tan-
tained at room temperature. The optimised reactions dem dimerisation reaction pathway, based on an intramo-
reached completion quickly (15–20 min), and moderate to lecular electrophilic aromatic substitution promoted by the
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Gold(I)-Catalysed Tandem Cyclisation
Table 2. Gold(I)-catalysed tandem cyclisation reactions of propargyl acetals and vinyl esters.[a]
[a] The reactions were performed with propargyl acetals 2a–2d (1 equiv.) and vinyl esters 3a–3d (3 equiv.) in CH2Cl2 (c ≈ 90 mm) together
with gold catalyst (5 mol-%). [b] Isolated as a mixture, which was separated later for full characterisation of the diastereomers, or as a
combination of pure products and mixtures. [c] Purification and characterisation was not possible for all or some of the products; cis/trans
ratio was calculated from the 1H NMR spectrum of the crude product mixture based on a comparison of chemical shift values of similar
products. [d] A 10% excess of acetal 2c relative to intermediate 3e was used; see the Exp. Sect. for details. [e] Ratio of acetal 2d/alkene
3a = 2:1; see the Exp. Sect. for details. [f] Ratio of acetal 2d/alkene 3a = 1:10; see the Exp. Sect. for details. [g] The preparation of product
14 could alternatively be carried out separately from acetal 2d and intermediate 3e (10% excess); see the Exp. Sect. for details. [h] Dimer
17 (2–4%) was isolated.
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H.-S. M. Siah, M. Kaur, N. Iqbal, A. Fiksdahl
FULL PAPER
Scheme 3. Possible mechanism for tandem dimerisation of p-methoxyphenylpropargyl acetal 2b (EAS = electrophilic aromatic substitu-
tion).
p-OMe substituent of the phenyl group, followed by [2+3] (16%, Table 2, entry line 4) could be isolated. Addition of
cycloaddition activated by the vinyl ether moiety of the in- further amounts of 2d (2d/3a = 2:1; standard ratio = 1:3)
termediate, is shown in Scheme 3. The final [2+3] cycload- to a reaction carried out at room temperature resulted in
dition took place in a stereoselective manner, as shown by the consumption of intermediate 3e, but only a slight in-
the relative stereochemistry (NOESY NMR spectra) of di- crease in the yields of tandem product 14 was observed
mer 17, which is consistent with previous observations.[9] (62%, Table 2, entry 12, line 1). By using a large excess of
The cis relationship of the OMe and Ph substituents on the the vinyl reactant (2d/3a = 1:10, –40 °C, Table 2, entry 12,
pentenyl ring of dimer 17, which is established in the final line 3), a 40% yield of intermediate 3e was isolated, which
[2+3] cycloaddition, is also consistent with the correspond- could be used in a separate new reaction with acetal 2d
ing 1,5-cis OMe/Ph configuration of tandem products 4–14. (Table 2, entry 13) or with a different propargyl reactant in
The lower yields of tandem products 6 and 7 seem to be the second step of the tandem reaction. Thus, the reaction
caused by the competing formation of dimer 17, indicating of intermediate 3e with p-Cl-phenyl propargyl acetal 2c
that the nucleophilicity of vinyl esters 3a and 3b is insuf- (10 mol-% excess of 2c) gave a high yield of mixed p-NO2/
ficient to favour attack on the less electrophilic gold inter- p-Cl tandem product 13 (76%; Table 2, entry 11). This dem-
mediate II (Scheme 2) and lead to the formation of tandem onstrates how the different effects of the electron-with-
compounds 6 and 7 as the major products.
drawing nitro group, i.e., activating for nucleophilic attack
An electron-withdrawing chloride substituent (as in 2c) but deactivating for the second step in the tandem cycli-
should increase the electrophilicity of gold intermediate II. sation, can be used strategically to lead to a selective cyclo-
The higher yields obtained of the corresponding tandem propanation, and so provide the possibility of introducing
products 9 and 10 (77–72%; Table 2, entries 7 and 8) dem- two different para phenyl substituents in mixed tandem
onstrate that an electron-withdrawing group on the phenyl products.
ring does tend to favour the tandem cycloaddition reaction
Tandem products 4–16 were formed as mixtures of two
pathway. The electron-withdrawing chloride substituent al- diastereomers (Table 1) in the cis/trans-cyclopropanation[8]
lows an easier nucleophilic attack on the gold(I) carbenoid and stereoselective pentaannulation[9] reactions. Due to
complex II by vinyl esters 3a and 3b, as well as by vinyl challenging chromatographic separations, the isolation of
ether intermediates IIIЈ in both the cycloaddition steps each diastereomer was sometimes demanding. A slight pref-
(Scheme 2).
erence for the formation of the cis isomer was observed,
We thought that an electron-withdrawing p-nitro substit- as had previously been seen for the cyclopropylations of
uent could assist in activating the gold intermediate in the propargyl substrates,[8] and consistent with the assumption
same way, and so allow easy nucleophilic attack of the vinyl that the cyclopropanation is controlled by the bulkier vin-
species. On the other hand, the second [2+3] cycloaddition ylic substituent.[5] However, varying the vinyl ester (OAc,
step might be hampered, since the cyclopropyl vinyl ether OBz) gave no significant difference in the isomeric ratios of
intermediate IIIЈ (Scheme 2) would be deactivated by the p- the products. In general, diastereomeric ratios were fairly
nitrophenyl moiety, and its nucleophilicity would be low (dr approx. 20–50), being lower when reactivity and
strongly decreased. The most successful reaction conditions yields were higher. The only reaction that gave a signifi-
discussed above were tested for the reactions of nitro deriva- cantly higher diastereoselectivity was the reaction between
tive 2d and vinyl acetate (3a). Both tandem product 14 deactivated methoxypropargyl substrate 2b and vinyl acet-
(58%) and intermediate 3e (20%) were produced at –40 °C ate (3a). The tandem product (i.e., 6; up to 39%) was
(Table 2, entry 12, line 2). At –78 °C, the reaction failed to formed with a consistent diastereoselectivity (dr approx. 70;
give any of the tandem product, and only intermediate 3e Table 2, entry 4) over all temperatures.
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Gold(I)-Catalysed Tandem Cyclisation
which was used as an internal standard. Coupling constants (J) are
reported in Hertz (Hz). The assignments of the chemical shifts were
determined using COSY, HMQC, HMBC, and NOESY experi-
ments. Melting points (m.p.) were determined using a Stuart appa-
ratus. Accurate mass determination in either positive or negative
mode was performed with a “Synapt G2-S” Q-TOF instrument
from Waters. Samples were ionised with an ASAP probe, and no
chromatographic separation was used before the mass analysis. IR
spectra were obtained using a Smart Endurance reflection cell.
Conclusions
To contribute to a better understanding of the chemistry
of propargyl acetals in the presence of gold(I), we have
studied chemoselective gold(I)-catalysed cycloadditions of
propargyl acetals 2a–2e and vinyl esters 3a–3e. We have
found that that such substrates follow a new tandem cycli-
sation pathway.
Although the propargyl acetals were expected to undergo
a gold(I)-catalysed [2+3] cycloaddition with vinyl sub-
strates,[9] the propargyl acetals and vinyl acetates studied
here were found to undergo an initial [1+2] cycloaddition
reaction to give cis-/trans-cyclopropanation intermediates
III by nucleophilic attack of the vinyl species at propargyl-
generated gold(I) carbenoid intermediates II. This different
chemoselectivity may be explained by the relatively elec-
tron-poor nature of the vinyl acetates, and this demon-
strates how varying the electronic nature of the vinylic reac-
tant can change the outcome of gold(I)-catalysed alkene–
propargyl cycloadditions.
With its activated vinyl ether moiety, intermediate III
may undergo a subsequent [2+3] cycloaddition with gold
carbenoid intermediates II, in which an additional pentenyl
ring is stereoselectively formed by a “C-1–C-3” cyclisation
pathway. The standard “C-3–C-1” would be the expected
reaction order,[9] and the observed “C-1–C-3”regioselectiv-
ity may be explained by the bulk of vinyl intermediate III.
The overall outcome of the reactions was therefore the
formation of cis/trans-cyclopropyl–cyclopentenyl tandem
products 4–16 by two sequential cycloaddition reactions, in-
volving two units of propargyl acetals 2a–2e and one unit
of vinyl esters 3a–3e. The highest tandem reactivity was ob-
served for propargyl substrates with a moderately electron-
withdrawing group (Cl) or with no substituent at the para
position of the phenyl moiety. Strongly electron-with-
drawing groups, or electron-donating groups, such as nitro
and methoxy groups, hamper selective parts of the tandem
process, resulting in a lower overall tandem reactivity.
The vinylic alkoxy group in cyclopropane intermediate
III, which activates it for the final cycloaddition with a sec-
ond unit of gold(I) carbenoid intermediate II, is the key
prerequisite of this tandem reaction, which enables the con-
struction of polysubstituted and highly functionalised bi-
cyclic compounds.
Preparation of the Propargyl Acetals: Propargyl acetals were syn-
thesised following a modified procedure starting from the appropri-
ate aldehyde or propargyl alcohol (compounds 1).[4,12] Propargyl
acetal 2f was synthesised following a literature procedure.[9]
{1-[(2-Methoxypropan-2-yl)oxy]prop-2-yn-1-yl}benzene (2a): A mix-
ture of 1-phenylprop-2-yn-1-ol (213.5 mg, 1.615 mmol) and 2-
methoxypropene (10.0 mL, 104 mmol) was cooled to 0 °C, then
pyridinium p-toluenesulfonate (catalytic amount) was added. The
cooling bath was removed, and the mixture was stirred at room
temperature for 4 h. The mixture was diluted with CH2Cl2 (20 mL),
washed with water (3ϫ 20 mL), dried with anhydrous MgSO4, fil-
tered, and concentrated in vacuo. The residue was purified by flash
chromatography (1:50 EtOAc/pentane) to give 2a (266.0 mg, 81%)
as a colourless oil. Rf = 0.78 (1:10 EtOAc/pentane). 1H NMR
(300 MHz, CDCl3): δ = 7.51–7.47 (m, 2 H, Harom), 7.38–7.7.26 (m,
3 H, Harom), 5.42 (d, J = 2.2 Hz, 1 H, CHCϵ), 3.18 (s, 3 H, OCH3),
2.53 (d, J = 2.3 Hz, 1 H, CϵCH), 1.54 (s, 3 H, CCH3) 1.33 (s, 3
H, CCH3) ppm. 13C NMR (400 MHz, CDCl3): δ = 140.3 (1 C,
Carom), 128.5 (2 C, CHarom), 128.0 (1 C, CHarom), 126.9 (2 C,
CHarom), 101.9 (1 C, OCOCH3), 84.5 (1 C, CHCϵ), 73.7 (1 C,
ϵCH), 62.6 (1 C, CHCϵ) 49.5 (1 C, OCH3), 25.4 (1 C, CCH3),
1
24.9 (1 C, CCH3) ppm. H and 13C NMR spectroscopic data are
consistent with literature data.[9]
1-(4-Methoxyphenyl)prop-2-yn-1-ol (1b): A solution of ethynylmag-
nesium bromide (0.50 m in THF; 19.0 mL, 9.5 mmol) was cooled
to –20 °C.
A solution of 4-methoxybenzaldehyde (1.0336 g,
7.5916 mmol) in dry THF (1.5 mL) was added, and the flask was
washed out with further THF (0.5 mL), which was added to the
reaction mixture. The cooling bath was removed, and the reaction
mixture was stirred at room temperature for 1 h. The reaction was
quenched by the addition of saturated aqueous ammonium chlor-
ide (10 mL), and the mixture was extracted with Et2O (2ϫ 20 mL).
The combined organic layers were dried with Na2SO4, filtered, and
concentrated in vacuo. The residue was purified by flash
chromatography (1:3 EtOAc/pentane) to give 1b (1.113 g, 90%) as
a pale yellow oil. Rf = 0.31 (1:3 EtOAc/pentane). 1H NMR
(300 MHz, CDCl3): δ = 7.51–7.46 (m, 2 H, Harom), 6.93–6.90 (m,
2 H, Harom), 5.43 (dd, J = 6.2, 2.1 Hz, CHCϵ), 3.82 (s, 3 H,
1
OCH3), 2.66 (d, J = 2.2 Hz, ϵCH), 2.10 (d, 6.2 Hz, OH) ppm. H
NMR spectroscopic data are consistent with literature data.[13]
Experimental Section
1-Methoxy-4-{1-[(2-methoxypropan-2-yl)oxy]prop-2-yn-1-yl}benz-
General Methods: All reactions were performed under a nitrogen
ene (2b): A mixture of 1b (1.113 g, 6.862 mmol) and 2-methoxypro-
atmosphere. Commercial grade reagents were used as received. 1- pene (25.0 mL, 261 mmol) was cooled to 0 °C, then pyridinium p-
Phenylvinyl acetate was synthesised following a literature pro-
toluenesulfonate (catalytic amount) was added. The cooling bath
was removed, and the mixture was stirred at room temperature for
cedure.[11] Dry solvents were collected from a solvent-purification
system. All reactions were monitored by GC and by thin-layer 90 min. The mixture was diluted with dichloromethane (100 mL),
chromatography (TLC) using silica gel 60 F254 plates (0.25 mm
thickness). Flash chromatography was carried out using silica gel
washed with water (3ϫ 100 mL), dried with anhydrous MgSO4,
filtered, and concentrated in vacuo. The residue was purified by
60 (0.040–0.063 mm). High-Throughput Flash Purification (HPFP) flash chromatography (gradient 1:50 to 1:20 EtOAc/pentane) to
was carried out using pre-packed cartridges. 1H and 13C NMR
spectra were recorded using 300 or 400 MHz spectrometers. Chemi-
cal shifts are reported in ppm (δ) downfield from tetramethylsilane,
give 2b (1.217 g, 76%) as a colourless oil. Rf = 0.57 (1:5 EtOAc/
pentane). H NMR (400 MHz, CDCl3): δ = 7.42 (d, J = 8.7 Hz, 2
H, Harom), 6.89 (d, J = 8.8 Hz, 2 H, Harom), 5.37 (d, J = 2.2 Hz, 1
1
Eur. J. Org. Chem. 2014, 1727–1740
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1733

H.-S. M. Siah, M. Kaur, N. Iqbal, A. Fiksdahl
FULL PAPER
H, CHCϵ), 3.80 (s, 3 H, PhOCH3), 3.18 (s, 3 H, COCH3), 2.54 (d,
= 5.9, 2.2 Hz, CHCϵ), 2.74 (d, J = 2.2 Hz, ϵCH), 2.43 (d, J =
J = 2.2 Hz, 1 H, CϵCH) 1.53 (s, 3 H, CCH3), 1.33 (s, 3 H, CCH3) 5.8 Hz, OH) ppm. 13C NMR (400 MHz, CDCl3): δ = 147.9 (1 C,
ppm. 13C NMR (400 MHz, CDCl3): δ = 159.4 (1 C, Carom), 132.5 Carom), 146.6 (1 C, Carom), 127.3 (2 C, CHarom), 123.8 (2 C,
(1 C, Carom), 128.3 (2 C, CHarom), 113.9 (2 C, CHarom), 101.8 (1 C, CHarom), 82.3 (1 C, Cϵ), 76.0 (1 C, ϵCH), 63.3 (1 C, C-OH) ppm.
OCOCH3), 84.7 (1 C, CHCϵ), 73.5 (1 C, ϵCH), 62.2 (1 C, CHCϵ)
55.3 (1 C, PhOCH3), 49.5 (1 C, OCH3), 25.4 (1 C, CCH3), 25.0 (1
1H and 13C NMR spectroscopic data are consistent with literature
data.[15]
C, CCH ) ppm. IR (thin film): ν = 3286, 2991, 1463, 1209, 968,
˜
3
1-{1-[(2-Methoxypropan-2-yl)oxy]prop-2-yn-1-yl}-4-nitrobenzene
(2d): A mixture of 1d (1.1091 g, 6.26 mmol) and 2-methoxypropene
(20.0 mL, 209 mmol) was cooled to 0 °C, then pyridinium p-tolu-
enesulfonate (catalytic amount) was added. The cooling bath was
removed, and the mixture was stirred at room temperature for 1 h.
The mixture was diluted with dichloromethane (100 mL), washed
with water (3ϫ 100 mL), dried with anhydrous MgSO4, filtered,
and concentrated in vacuo. The residue was purified by flash
chromatography (1:50 EtOAc/pentane) to give 2d (1.335 g, 86%) as
a colourless oil. Rf = 0.10 (1:50 EtOAc/pentane). 1H NMR
(400 MHz, CDCl3): δ = 8.24–8.22 (m, 2 H, Harom), 7.69 (m, 2 H,
CHarom), 5.52 (d, J = 2.2 Hz, 1 H, CHCϵ), 3.18 (s, 3 H, OCH3),
2.58 (d, J = 2.3 Hz, 1 H, CϵCH), 1.56 (s, 3 H, CCH3), 1.34 (s, 3
H, CCH3) ppm. 13C NMR (400 MHz, CDCl3): δ = 147.6 (1 C,
826, 637 cm–1. HRMS (EI): calcd. for C14H18O3 234.1250; found
234.1250.
1-(4-Chlorophenyl)prop-2-yn-1-ol (1c): A solution of ethynylmagne-
sium bromide (0.50 m in THF; 18 mL, 9.0 mmol) was cooled to
–20 °C. A solution of 4-chlorobenzaldehyde (1.0105 g, 7.19 mmol)
in THF (2.5 mL) was added, and the flask washed out with more
THF (0.5 mL), which was then added to the reaction mixture. The
cooling bath was removed, and the reaction mixture was stirred at
room temperature for 5 min. The reaction was quenched by the
addition of saturated aqueous ammonium chloride (10 mL), and
the mixture was extracted with Et2O (2ϫ 20 mL). The combined
organic extracts were dried with Na2SO4, filtered, and concentrated
in vacuo. The residue was purified by flash chromatography (gradi-
ent 1:10–1:3 EtOAc/pentane) to give 1c (1.078 g, 90%) as a pale
yellow oil. Rf = 0.47 (1:3 EtOAc/pentane). 1H NMR (400 MHz,
CDCl3): δ = 7.51–7.48 (m, 2 H, Harom), 7.38–7.35 (m, 2 H, Harom),
5.45 (dd, J = 6.1, 2.1 Hz, CHCϵ), 2.68 (d, J = 2.2 Hz, ϵCH), 2.21
Carom-NO2), 147.3 (1 C, Carom), 127.5 (2 C, CHarom), 123.8 (2 C,
CHarom), 102.2 (1 C, OCOCH3), 83.1 (1 C, CHCϵ), 74.7 (1 C,
ϵCH), 61.6 (1 C, CHCϵ), 49.6 (1 C, OCH3), 25.3, (1 C, CCH3),
24.8 (1 C, CCH ) ppm. IR (thin film): ν = 3257, 2992, 2940, 2857,
˜
3
1517, 1343, 1211, 1186, 1145, 1030, 852, 701 cm–1. HRMS (EI):
1
(d, J = 6.1 Hz, OH) ppm. H NMR spectroscopic data are consis-
calcd. for [M – CH3O]+ 218.0817; found 218.0815.
tent with literature data.[14]
3-[(2-Methoxypropan-2-yl)oxy]but-1-yne (2e): A mixture of 3-but-
yn-2-ol (513.0 mg, 7.319 mmol) and 2-methoxypropene (10.0 mL,
104 mmol) was cooled to 0 °C, then pyridinium p-toluenesulfonate
(catalytic amount) was added. The cooling bath was removed, and
the mixture was stirred at room temperature for 1 h. The mixture
was diluted with diethyl ether (25 mL), washed with water (3ϫ
25 mL), dried with anhydrous MgSO4, filtered, and concentrated
in vacuo. The residue was purified by flash chromatography (1:20
Et2O/pentane) to give 2e (668.6 mg, 64%) as a colourless oil. Rf =
0.58 (1:20 Et2O/pentane). 1H NMR (400 MHz, CDCl3): δ = 4.49
(dq, J = 6.7, 2.0 Hz, 1 H, CHCϵ), 3.24 (s, 3 H, OCH3), 2.36 (d, J
= 2.0 Hz, 1 H, ϵCH), 1.45 (s, 3 H, CCH3), 1.43 (d, J = 6.7 Hz, 3
H, CH3CCϵ), 1.36 (s, 3 H, CCH3) ppm. 13C NMR (400 MHz,
CDCl3): δ = 101.1 (1 C, OCOCH3), 86.1 (1 C, CHCϵ), 71.3 (1 C,
ϵCH), 56.3 (1 C, CHCϵ), 49.1 (1 C, OCH3), 25.4 (1 C, Me-
OCCH3), 24.6 (1 C, MeOCCH3), 23.4 (1 C, CHCH3) ppm. 1H and
13C NMR spectroscopic data are consistent with literature data.[9]
1-Chloro-4-{1-[(2-methoxypropan-2-yl)oxy]prop-2-yn-1-yl}benzene
(2c): A mixture of 1c (1.078 g, 6.47 mmol) and 2-methoxypropene
(20.0 mL, 209 mmol) was cooled to 0 °C, then pyridinium p-tolu-
enesulfonate (catalytic amount) was added. The cooling bath was
removed, and the mixture was stirred at room temperature for 2 h.
The mixture was diluted with dichloromethane (100 mL), washed
with water (3ϫ 100 mL), dried with anhydrous MgSO4, filtered,
and concentrated in vacuo. The residue was purified by flash
chromatography (1:30 EtOAc/pentane) to give 2c (1.3234 g, 86%)
as a colourless oil. Rf = 0.28 (1:30 EtOAc/pentane). 1H NMR
(400 MHz, CDCl3): δ = 7.43 (d, J = 8.4 Hz, 2 H, Harom), 7.33 (d,
J = 8.5 Hz, 2 H, CHarom), 5.39 (d, J = 2.2 Hz, 1 H, CHCϵ), 3.17
(s, 3 H, OCH3), 2.54 (d, J = 2.2 Hz, 1 H, CϵCH), 1.53 (s, 3 H,
CCH3), 1.32 (s, 3 H, CCH3) ppm. 13C NMR (400 MHz, CDCl3):
δ = 138.9 (1 C, Carom), 133.8 (1 C, Carom), 128.7 (2 C, CHarom),
128.2 (2 C, CHarom), 102.0 (1 C, OCOCH3), 84.0 (1 C, CHCϵ),
74.0 (1 C, ϵCH), 61.9 (1 C, CHCϵ), 49.5 (1 C, OCH3), 25.4, (1
Tandem Cyclisation Reactions
C, CCH ), 24.9 (1 C, CCH ) ppm. IR (thin film): ν = 3296, 1210,
˜
3
3
1146, 1092, 842, 633 cm–1. HRMS (EI): calcd. for C12H11OCl [M –
General Procedure: The gold catalyst ({Au[P(tBu)2(o-biphenyl)-
CH3CN]}SbF6, 5 mol-%) was dissolved in dry CH2Cl2 (1.5 mL),
and the solution was stirred under a nitrogen atmosphere at the
required temperature. The appropriate propargyl acetal (com-
pounds 1a–1d) and vinyl ester or alkene (3 equiv.) were dissolved
in dry CH2Cl2 (1.0 mL), and this solution was added to the solu-
tion of the gold catalyst. The flask was washed out with further
dry CH2Cl2 (2ϫ 0.5 mL), and this was added to the mixture. When
the acetal had been consumed, the reaction was quenched with
NEt3 (5 drops), the mixture was filtered through CeliteTM, and the
filtrate was concentrated in vacuo. The residue was purified by flash
chromatography using an appropriate eluent system to give the de-
sired tandem products.
CH4O]+ 206.0493; found 206.0490.
1-(4-Nitrophenyl)prop-2-yn-1-ol (1d): A solution of ethynylmagne-
sium bromide (0.50 m in THF; 16 mL, 8.0 mmol) was cooled to
–20 °C. A solution of 4-nitrobenzaldehyde (1.0296 g, 6.8135 mmol)
in THF (10 mL) was added, and the flask was washed out with
THF (a total of 5 mL), which was then added to the reaction mix-
ture. The cooling bath was removed, and the reaction mixture was
stirred at room temperature for 30 min. The reaction was quenched
by the addition of saturated aqueous ammonium chloride (10 mL),
and the mixture was diluted with Et2O (50 mL), water (25 mL),
and EtOAc (50 mL). The phases were separated, and the aqueous
phase was extracted with EtOAc (50 mL). The combined organic
extracts were dried with Na2SO4, filtered, and concentrated in
vacuo. The residue was purified by flash chromatography (1:4
EtOAc/pentane) to give 1d (1.1091 g, 92%) as a pale yellow oil. Rf
= 0.17 (1:4 EtOAc/pentane). 1H NMR (400 MHz, CDCl3): δ =
cis-/trans-2-(1,3-Dimethoxy-4,5-diphenylcyclopent-2-en-1-yl)cyclo-
propyl Acetate (cis-/trans-4): Compounds cis-4 and trans-4 were
synthesised following the general procedure, using gold catalyst
(13.0 mg, 16.8 μmol), compound 2a (73.5 mg, 360 μmol), and vinyl
8.27–8.23 (m, 2 H, Harom), 7.75–7.73 (m, 2 H, Harom), 5.58 (dd, J acetate (85.1 mg, 989 μmol), at –78 °C for 15 min. The products
1734
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 1727–1740

Gold(I)-Catalysed Tandem Cyclisation
were purified using an eluent system of 1:20 EtOAc/pentane to give
a 1:1 mixture of compounds cis-4 and trans-4 (47.2 mg, 69%) as a
yellow oil.
C=CHCOCH3), 22.9 (1 C, CHCHOBz), 9.1 (1 C, CH2) ppm. IR
(neat): ν = 2927, 1722, 1644, 1452, 1272, 709 cm–1. HRMS (EI):
˜
calcd. for C29H28O4 [M]+ 440.1982; found 440.1979.
Data for cis-4: Rf = 0.36 (1:10 EtOAc/pentane). 1H NMR
Data for trans-5: Rf = 0.64 (CH2Cl2). 1H NMR (400 MHz, CDCl3):
(400 MHz, CDCl3): δ = 7.38–7.26 (m, 10 H, Harom), 4.85 (dd, J = δ = 8.03 (d, J = 7.2 Hz, 2 H, CHo-OBz), 7.56 (t, J = 7.4 Hz, 1 H,
2.3, 1.5 Hz, 1 H, C=CH), 4.44 (s, 1 H, C=CHCH), 4.06 (d, J = CHp-OBz), 7.45–7.40 (m, 2 H, CHm-OBz), 7.34–7.23 (m, 10 H,
1.2 Hz, 1 H, C=CHCH), 4.00 (dt, J = 7.1, 4.2 Hz, 1 H, CHOAc),
3.70 (s, 3 H, C=COCH3), 3.04 (s, 3 H, C=CHCOCH3), 2.09 (s, 3 1.9 Hz, 1 H, C=CH), 4.34 (s, 1 H, C=CH), 4.09 (s, 1 H, C=CHCH),
H, COOCH3), 0.91 (ddd, J = 8.2, 6.6, 4.2 Hz, 1 H, AcOCHCH2), 3.23 (s, 3 H, C=COCH3), 2.46 (s, 3 H, C=CHCOCH3), 1.63 (m, 1
CHarom), 4.70 (dt, J = 7.0, 4.6 Hz, 1 H, CHOBz), 4.55 (t, J =
0.81 (dt, J = 10.2, 6.8 Hz, 1 H, AcOCHCH2), 0.39 (ddd, J = 10.2, H, BzOCHCH2), 1.59 (m, 1 H, BzOCHCH), 1.28 (m, 1 H,
8.2, 7.2 Hz, 1 H, AcOCHCH) ppm. 13C NMR (400 MHz, CDCl3):
δ = 171.2 (1 C, OC=O), 159.7 (1 C, C=COCH3), 141.2 (1 C,
BzOCHCH2) ppm. 13C NMR (400 MHz, CDCl3): δ = 167.3 (1 C,
OC=O), 158.8 (1 C, C=COCH3), 141.4 (1 C, CaromCHC=), 137.9
CaromCHCHC=), 137.6 (1 C, CaromCHC=), 129.7 (2 C, o-CHarom), (1 C, CaromCHCHC=), 133.2, (1 C, CHp-OBz), 130.7 (2 C, CHarom),
129.4 (2 C, o-CHarom), 128.0 (2 C, m-CHarom), 127.8 (2 C, m-
CHarom), 126.9 (1 C, p-CHarom), 126.4 (1 C, p-CHarom), 99.7 (1 C,
130.0 (1 C, OCOCarom-OBz), 129.6 (2 C, CHo-OBz), 129.6 (1 C,
CHarom), 128.4 (2 C, CHm-OBz), 127.8 (2 C, CHarom), 127.4 (2 C,
C=CH), 86.8 (1 C, C=CHCOCH3), 60.3 (1 C, C=CHCH), 56.7 CHarom), 126.6 (2 C, CHarom), 126.2 (1 C, CHarom), 97.6 (1 C,
(=COCH3), 53.2 (1 C, CHOAc), 53.1 (1 C, C=CHCH), 51.8 (1 C,
C=CHCOCH3), 21.7 (1 C, OOCCH3), 21.2 (1 C, CHCHOAc), 9.2
C=CH), 84.9 (1 C, C=CHCOCH3), 59.3 (1 C, C=CHCH), 56.5 (1
C, C=CHCH), 56.2 (1 C, C=COCH3), 52.4 (1 C, CHCOCH3), 51.9
(1 C, CHOBz), 24.8 (1 C, CHCHOBz), 9.8 (1 C, CH2) ppm. IR
(1 C, CH CHOAc) ppm. IR (thin film): ν = 3034, 2940, 2826, 1742,
˜
2
1228, 701 cm–1. HRMS (EI): calcd. for C24H26O4 [M]+ 378.1831; (thin film): ν = 3012, 2930, 1714, 1662, 1267, 716, 696 cm–1. HRMS
˜
found 378.1828.
(EI): calcd. for C29H28O4 [M]+ 440.1982; found 440.1982.
Data for trans-4: Rf = 0.32 (1:10 EtOAc/pentane). 1H NMR
cis-/trans-2-[1,3-Dimethoxy-4,5-bis(4-methoxyphenyl)cyclopent-2-
(400 MHz, CDCl3): δ = 7.39–7.37 (m, 2 H, Harom), 7.32–7.20 (m, en-1-yl]cyclopropyl Acetate (cis-/trans-6): Compounds cis-6 and
8 H, Harom), 4.66 (t, J = 2.0 Hz, 1 H, C=CH), 4.46 (dt, J = 7.4, trans-6 were synthesised following the general procedure, using
4.0 Hz, 1 H, CHOAc), 4.17 (br. s, 1 H, C=CHCH), 4.01 (br. s, 1 gold catalyst (13.3 mg, 17.2 μmol), compound 2b (80.7 mg,
H, C=CHCH), 3. 60 (s, 3 H, C=COCH3 ), 2.47 (s, 3 H, 344 μmol), and vinyl acetate (89.6 mg, 1.04 mmol), at –40 °C for
C=CHCOCH3), 2.10 (s, 3 H, COOCH3), 1.47–1.36 (m, 2 H, Ac-
OCHCH2 and AcOCHCH), 1.17–1.11 (m, 1 H, AcOCHCH2) ppm.
13C NMR (400 MHz, CDCl3): δ = 171.6 (1 C, C=O), 159.1 (1 C,
C=CH), 141.3 (1 C, C=CHCHCarom), 137.8 (1 C, C=CHCarom),
130.9 (2 C, C=CHCHCCHarom), 129.8 (2 C, C=CHCCHarom),
127.7 (2 C, m-CHarom), 127.4 (2 C, m-CHarom), 126.6 (1 C, p-
CHarom), 126.2 (1 C, p-CHarom), 97.5 (1 C, C=CH), 84.9 (1 C,
CH3OCH), 58.0 (1 C, PhCH), 57.3 (1 C, PhCH), 56.5 (1 C,
CH3OC=), 52.3 (1 C, CH3OCH), 51.9 (1 C, AcOCH), 24.5 (1 C,
AcOCHCH), 20.8 (1 C, OCOCH3), 9.2 (1 C, CH2) ppm. IR (thin
30 min. The products were purified using an eluent system of 1:3
Et2O/pentane to give a 87:13 mixture of compounds cis-6 and
trans-6 (29.3 mg, 39%).
1
Data for cis-6: Rf = 0.19 (1% THF/CH2Cl2). Yellow oil. H NMR
(400 MHz, CDCl3): δ = 7.25–7.23 (m, 2 H, C=CHCCHarom),
7.18–7.16 (m, 2 H, C=CHCCHCCHarom), 6.87–6.85 (m, 2 H,
C=CHCCHCHarom), 6.85–6.84 (m,
2 H, C=CHCCHCCH-
CHarom), 4.80–4.79 (m, 1 H, C=CH), 4.37 (br. s, 1 H, C=CH),
4.05–4.00 (m, 1 H, CHOAc), 3.99 (br. s, C=CHCH), 3.80 (s, 3 H,
CH3O-PhCHC=), 3.78 (s, 3 H, CH3O-PhCHCCH=), 3.68 (s, 3 H,
C=COCH3), 3.04 (s, 3 H, C=CHCOCH3), 2.10 (s, 3 H, OCOCH3),
0.92–0.87 (m, 1 H, CH2), 0.85–0.79 (m, 1 H, CH2), 0.42–0.36 (m,
1 H, CHCHOAc) ppm. 13C NMR (400 MHz, CDCl3): δ = 171.1
(1 C, OC=O), 159.6 (1 C, C=COCH3), 158.5 (1 C, MeO-Carom),
158.1 (1 C, MeO-Carom), 133.1 (1 C, C=CHCCHCarom), 130.5 (2
C, C=CHCCHCCHarom), 130.2 (2 C, C=CHCCHarom), 129.4 (1 C,
C=CHCarom), 113.4 (2 C, C=CHCCHCCHCHarom), 113.1 (2 C,
C=CHCCHCHarom), 99.7 (1 C, C=CH), 86.6 (1 C, C=CHCH),
59.5 (1 C, C=CH), 56.6 (1 C, C=COCH3), 55.1 (1 C, CH3OPh),
55.1 (1 C, CH3OPh), 53.2 (1 C, CHOAc), 51.9 (1 C, C=CHCH),
51.8 (1 C, C=CHCOCH3), 21.5 (1 C, CHCHOAc), 21.2 (1 C, OC-
film): ν = 3023, 2935, 2826, 1745, 1227, 1035, 701 cm–1. HRMS
˜
(EI): calcd. for C23H23O3 [M – CH3O]+ 347.1647; found 347.1647.
cis-/trans-2-(1,3-Dimethoxy-4,5-diphenylcyclopent-2-en-1-yl)cyclo-
propyl Benzoate (cis-/trans-5): Compounds cis-5 and trans-5 were
synthesised following the general procedure, using gold catalyst
(13.2 mg, 16.8 μmol), compound 2a (68.2 mg, 334 μmol), and vinyl
benzoate (152.0 mg, 1.03 mmol), at –78 °C for 20 min. The prod-
ucts were purified using an eluent system of 1:1 CH2Cl2/pentane
then CH2Cl2 to give cis-5 (25.7 mg, 34%) as a colourless solid and
trans-5 (23.0 mg, 31%) as a yellow oil.
Data for cis-5: Rf = 0.57 (CH2Cl2), m.p. 154–158 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.04 (dd, J = 8.3, 1.3 Hz, 2 H, CHo-OBz),
7.59 (t, J = 7.4 Hz, 1 H, CHp-OBz), 7.46 (t, J = 7.7 Hz, 2 H,
CHm-OBz), 7.23–7.35 (m, 10 H, CHarom), 4.99 (dd, J = 2.2, 1.3 Hz,
OCH ), 9.1 (1 C, CH ) ppm. IR (thin film): ν = 2934, 1742, 1609,
˜
3
2
1509, 1463, 1227, 1175, 830, 729 cm–1. HRMS (EI): calcd. for
C26H30O6 [M]+ 438.2042; found 438.2038.
1 H, C=CH), 4.40 (s, 1 H, C=CHCH), 4.17 (s, 1 H, C=CHCH), Data for trans-6: Rf = 0.15 (1% THF/CH2Cl2). Yellow oil. 1H
4.08 (dt, J = 7.1, 4.2 Hz, CHOBz), 3.73 (s, 3 H, C=COCH3), 3.16
(s, 3 H, C=CHCOCH3), 1.11 (ddd, J = 8.1, 6.4, 4.2 Hz, 1 H, CH2),
0.97 (dt, J = 10.1, 6.7 Hz, 1 H, CH2) 0.58 (ddd, J = 10.1 8.2, 7.1 Hz,
1 H, BzOCHCH) ppm. 13C NMR (400 MHz, CDCl3): δ = 167.2
NMR (300 MHz, CDCl3): δ = 7.29–7.26 (m, 2 H, C=CHCCHarom),
7.22–7.19 (m, 2 H, C=CHCCHCCHarom), 6.86–6.85 (m, 2 H,
C=CHCCHCHarom), 6.83–6.82 (m,
2
H, C=CHCCH-
CCHCHarom), 4.61–4.60 (m, 1 H, C=CH), 4.47–4.41 (m, 1 H,
(1 C, C=O), 160.2 (1 C, C=COCH3), 140.6 (1 C, CaromCHCHC=), CHOAc), 4.08 (br. s, 1 H, C=CH), 3.95 (br. s, C=CHCH), 3.80 (s,
137.7 (1 C, CaromCHC=), 133.1 (1 C, CHp-OBz), 130.3 (1 C, 3 H, CH3O-Ph), 3.79 (s, 3 H, CH3O-Ph), 3.59 (s, 3 H, C=COCH3),
Carom-OBz), 129.6 (2 C, CHo-OBz), 129.5 (1 C, CHarom), 129.1 (2 C, 2.52 (s, 3 H, C=CHCOCH3), 2.10 (s, 3 H, OCOCH3), 1.41–1.31
CHarom), 128.4 (2 C, CHm-OBz), 128.1 (2 C, CHarom), 127.7 (2 C,
(m, 1 H, CH2), 1.41–1.31 (m, 1 H, CHCHOAc), 1.16–1.09 (m, 1
CHarom), 127.0 (1 C, Carom), 126.4 (2 C, CHarom), 99.3 (1 C, H, CH2) ppm. 13C NMR (400 MHz, CDCl3): δ = 171.6 (1 C,
C=CH), 86.2 (1 C, C=CHCOCH3), 59.8 (1 C, C=CHCH), 56.8 OC=O), 159.1 (1 C, C=COCH3), 158.3 (1 C, MeO-Carom), 158.1 (1
(=COCH3), 54.5 (1 C, C=CHCH), 53.5 (1 C, CHOBz), 52.0 (1 C, C, MeO-Carom), 133.5 (1 C, C=CHCCHCarom), 131.5 (2 C,
Eur. J. Org. Chem. 2014, 1727–1740
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1735

H.-S. M. Siah, M. Kaur, N. Iqbal, A. Fiksdahl
C=CHCCHCCHarom), 130.6 (2 C, C=CHCCHarom), 129.9 (1 C, 1175, 1035, 711 cm–1. HRMS (EI): calcd. for C31H32O6 [M]+
FULL PAPER
C=CHCarom), 113.2 (2 C, MeO-CCHarom), 112.9 (2 C, MeO-
CCHarom), 97.4 (1 C, C=CH), 84.6 (1 C, C=CHCH), 57.0 (1 C,
C=CH), 56.6 (1 C, C=COCH3), 56.5 (1 C, C=CHCH), 55.2 (1 C,
CH3OPh), 55.1 (1 C, CH3OPh), 52.4 (1 C, C=CHCOCH3), 51.9 (1
C, CHOAc), 24.3 (1 C, CHCHOAc), 20.8 (1 C, OCOCH3), 9.2 (1
500.2199; found 500.2196.
cis-/trans-2-[1,3-Dimethoxy-4,5-bis(4-methoxyphenyl)cyclopent-2-
en-1-yl]-1-phenylcyclopropyl Acetate (cis-/trans-8): Compounds cis-
8 and trans-8 were synthesised following the general procedure,
using gold catalyst (10.5 mg, 13.6 μmol), compound 2b (63.0 mg,
269 μmol), and 1-phenylvinyl acetate (128.0 mg, 0.789 mmol), at
–40 °C for 30 min, then 0 °C for 15 min. The products were purified
using an eluent system of 1:10 EtOAc/pentane to give a 1:3 mixture
of compounds cis-8 and trans-8 (26.0 mg, 19%).
C, CH ) ppm. IR (thin film): ν = 2930, 2826, 1743, 1609, 1511,
˜
2
1246, 1177, 1034 cm–1. HRMS (EI): calcd. for C26H30O6 [M]+
438.2042; found 438.2044.
cis-/trans-2-[1,3-Dimethoxy-4,5-bis(4-methoxyphenyl)cyclopent-2-
en-1-yl]cyclopropyl Benzoate (cis-/trans-7): Compounds cis-7 and
trans-7 were synthesised following the general procedure, using
gold catalyst (13.7 mg, 17.7 μmol), compound 2b (80.7 mg,
344 μmol), and vinyl benzoate (152.6 mg, 1.03 mmol), at –78 °C for
120 min. The products were purified using an eluent system of 1:9
Et2O/pentane to give a 63:37 mixture of compounds cis-7 and
trans-7 (49.5 mg, 53%).
1
Data for cis-8: Rf = 0.25 (1% Et2O/CH2Cl2). Yellow oil. H NMR
(400 MHz, CDCl3): δ = 7.33–7.28 (m, 2 H, C=CHCCHCCHarom),
7.16–7.08 (m, 2 H, C=CHCCHarom), 7.16–7.08 (m, 2 H, CHm-Ph),
7 . 1 6 – 7 . 0 8 ( m , 2 H , C H p - P h ) , 6 . 8 9 – 6 . 8 7 ( m , 2 H ,
C=CHCCHCCHCHarom), 6.73–6.71 (m, 2 H, CHo-Ph), 6.65–6.63
(m, 2 H, C=CHCCHCHarom), 4.90 (br. s, 1 H, C=CH), 4.31 (br. s,
1 H, C=CH), 4.14 (br. s, 1 H, C=CHCCH), 3.82 (s, 3 H, CH3OPh),
3.71 (s, 3 H, CH3OPh), 3.67 (s, 3 H, C=COCH3), 3.15 (s, 3 H,
C=CHCOCH3), 1.62–1.60 (m, 2 H, CH2), 2.17 (s, 3 H, OCOCH3),
0.74–0.69 (m, 1 H, CHCOAc) ppm. 13C NMR (400 MHz, CDCl3):
δ = 170.1 (1 C, C=O), 160.6 (1 C, MeOCarom), 158.4 (1 C, C=),
158.2 (1 C, MeOCarom), 141.4 (1 C, CaromCOAc), 132.5 (1 C,
C=CHCCHCarom), 130.3 (2 C, C=CHCCHarom), 129.9 (2 C,
C=CHCCHCCHarom), 129.4 (1 C, C=CHCarom), 127.9 (2 C,
CHm-Ph), 126.1 (1 C, CHp-Ph), 123.4 (2 C, CHo-Ph), 113.6 (2 C,
C=CHCCHCHarom), 113.3 (2 C, C=CHCCHCCHCHarom), 98.7 (1
C, C=CH), 86.6 (1 C, C=CHC), 62.0 (1 C, COAc), 58.2 (1 C,
C=CH), 56.8 (1 C, MeOPh), 55.2 (1 C, MeOPh), 55.1 (1 C,
C=COCH3), 53.8 (1 C, C=CHCCH), 52.2 (1 C, C=CHCOCH3),
34.9 (1 C, CHCOAc), 21.5 (1 C, OCOCH3), 19.0 (1 C, CH2) ppm.
Data for cis-7: Rf = 0.09 [1:4 (1:20 EtOAc/pentane)/CH2Cl2]; yellow
oil. 1H NMR (400 MHz, CDCl3): δ = 8.04–8.02 (m, 2 H, CHo-OBz),
7.60–7.56 (m, 1 H, CHp-OBz), 7.48–7.44 (m, 2 H, CHm-OBz), 7.24–
7.22 (m, 2 H, C=CHCCHCCHa ro m), 7.22–7.19 (m, 2 H,
CH=CCHCCHarom), 6.86–6.84 (m, 2 H, CH=CCHCCHCHarom),
6.80–6.78 (m, 2 H, C=CHCCHCCHCHarom), 4.93–4.92 (m, 1 H,
C=CH), 4.35 (br. s, 1 H, CH=CCH), 4.15–4.10 (m, 1 H, CHOBz),
4.091–4.088 (m, 1 H, C=CHCCH), 3.79 (s, 3 H, CH3OPh), 3.78 (s,
3 H, CH3OPh), 3.72 (s, 3 H, C=COCH3), 3.15 (s, 3 H, C=COCH3),
1.12–1.07 (m, 1 H, CH2), 0.99–0.93 (m, 1 H, CH2), 0.61–0.54 (m,
1 H, CHCHOAc) ppm. 13C NMR (400 MHz, CDCl3): δ = 167.2
(1 C, Carom-OBz), 160.1 (1 C, C=CH), 158.6 (1 C, CH3OCarom),
158.1 (1 C, CH3OCarom), 133.0 (1 C, CHp-OBz), 132.6 (1 C,
C=CHCCHCarom), 130.4 (2 C, CH=CCHCCHarom), 130.3 (1 C,
COBz), 129.9 (2 C, C=CHCCHCCHarom), 129.6 (1 C, CH=CCH-
Carom), 129.5 (2 C, CHo-OBz), 128.4 (2 C, CHm-OBz), 113.6 (2 C,
CH=CCHCCHCHarom), 113.1 (2 C, C=CHCCHCCHCHarom),
99.3 (1 C, C=CH), 86.1 (1 C, C=CHC), 59.0 (1 C, CH=CCH), 56.7
(1 C, =COCH3), 55.2 (1 C, CH3OCarom), 55.1 (1 C, CH3OCarom),
53.5 (1 C, CHOBz), 53.3 (1 C, C=CHCCH), 51.9 (1 C,
C=CHCOCH3), 22.7 (1 C, CHCHOAc), 9.0 (1 C, CH2) ppm. IR
Data for a mixture of cis-8 and trans-8: IR (thin film): ν = 2930,
˜
2831, 1751, 1652, 1610, 1510, 1244, 1176, 1034, 731 cm–1. HRMS
(EI): calcd. for C32H24O6 [M]+ 514.2355; found 514.2346.
Data for trans-8: Rf = 0.30 (1 % Et2O/CH2Cl2). Yellow oil. 1H
NMR (400 MHz, CDCl3): δ = 7.46–7.44 (m, 2 H, CHo-Ph), 7.33–
7.30 (m, 2 H, CHm-Ph), 7.33–7.30 (m, 2 H, CHp-Ph), 7.26–7.24 (m,
2 H, C=CHCCHarom), 6.94–6.92 (m, 2 H, C=CHCCHCHarom),
6.67–6.65 (m, 2 H, C=CHCCHCCHCHarom), 6.47–6.45 (m, 2 H,
C=CHCCHCCHarom), 4.60 (br. s, 1 H, C=CH), 4.22 (br. s, 1 H,
C=CH), 3.85 (s, 3 H, CH3OPh), 3.75 (s, 3 H, CH3OPh), 3.62 (s, 3
H, C=COCH3), 3.31 (br. s, 1 H, C=CHCCH), 2.99 (s, 3 H,
C=CHCOCH3), 1.83–1.80 (m, 1 H, CH2), 1.80 (s, 3 H, OCOCH3),
1.46–1.41 (m, 1 H, CHCOAc), 1.28–1.24 (m, 1 H, CH2) ppm. 13C
NMR (400 MHz, CDCl3): δ = 169.9 (1 C, C=O), 160.2 (1 C, C=),
(thin film): ν = 2951, 2930, 2826, 1721, 1510, 1270, 1245, 1175,
˜
1110, 1034, 712 cm–1. HRMS (EI): calcd. for C31H32O6 [M]+
500.2199; found 500.2199.
Data for trans-7: Rf = 0.13 [1:4 (1:20 EtOAc/pentane)/CH2Cl2]; yel-
low oil. 1H NMR (400 MHz, CDCl3): δ = 8.03–8.01 (m, 2 H,
CHo-OBz), 7.58–7.53 (m, 1 H, CHp-OBz), 7.44–7.39 (m, 2 H,
CHm-OBz), 7.28–7.25 (m, 2 H, CH3OCCHCHarom), 7.24–7.21 (m, 2
H, CH3OCCHCHarom), 6.84–6.81 (m, 4 H, CHaromCOCH3), 4.71–
4.65 (m, 1 H, CHOBz), 4.51–4.49 (m, 1 H, C=CH), 4.25 (br. s, 1
H, CH=CCH), 4.04 (br. s, 1 H, C=CHCCH), 3.79 (s, 3 H,
CH3OPh), 3.77 (s, 3 H, CH3OPh), 3.24 (s, 3 H, =COCH3), 2.52 (s,
3 H, =CHCOCH3), 1.62–1.50 (m, 1 H, CH2), 1.62–1.50 (m, 1 H,
CHCHOBz), 0.88–0.83 (m, 1 H, CH2) ppm. 13C NMR (400 MHz,
CDCl3): δ = 167.2 (1 C, Carom-OBz), 158.7 (1 C, C=CH), 158.3 (1
C, CH3 OCa r o m ), 158.0 (1 C, CH3 OCa r o m ), 133.5 (1 C,
C=CHCCHCarom), 133.1 (1 C, Cp-OBz), 131.6 (2 C, CH3OCCH-
CHarom), 130.5 (2 C, CH3OCCHCHarom), 129.9 (1 C, CH=
CCHCarom), 129.6 (2 C, CHo-OBz), 129.5 (1 C, Carom-OBz), 128.4 (2
C, CHm-OBz), 113.2 (2 C, CH3OCCHarom), 112.9 (2 C, CH3-
158.5 (1 C, MeOCarom), 157.9 (1 C, MeOCarom), 136.7 (1 C, Carom
-
C OA c ) , 1 3 2 . 5 ( 1 C , C = C H C C H C a r o m ) , 1 3 1 . 4 ( 2 C ,
C = C H C C H a r o m ) , 1 3 0 . 1 ( 2 C , C H p - P h ) , 1 3 0 . 0 ( 2 C ,
C=CHCCHCCHarom), 129.8 (1 C, C=CHCarom), 127.8 (2 C,
CHm-Ph), 127.6 (1 C, CHp-Ph), 113.5 (2 C, C=CHCCHCHarom),
112.8 (2 C, C=CHCCHCCHCHarom), 98.7 (1 C, C=CH), 85.5 (1
C, C=CHC), 63.9 (1 C, COAc), 58.7 (1 C, C=CH), 56.6 (1 C,
C=COCH3), 55.3 (1 C, MeOPh), 55.1 (1 C, MeOPh), 52.0 (1 C,
C=CHCOCH3), 51.8 (1 C, C=CHCCH), 30.2 (1 C, CHCOAc),
21.5 (1 C, OCOCH ), 15.9 (1 C, CH ) ppm. IR (thin film): ν =
˜
3
2
2997, 2935, 2831, 1750, 1652, 1610, 1510, 1243, 1176, 1034,
731 cm–1. HRMS (EI): calcd. for C32H34O6 [M]+ 514.2355; found
514.2346.
OCCHarom), 97.6 (1 C, C=CH), 84.5 (1 C, C=CHC), 58.3 (1 C, cis-/trans-2-[4,5-Bis(4-chlorophenyl)-1,3-dimethoxycyclopent-2-en-1-
CH=CCH), 56.2 (1 C, =COCH3), 55.6 (1 C, C=CHCCH), 55.13 yl]cyclopropyl Acetate (cis-/trans-9): Compounds cis-9 and trans-9
(1 C, CH3 OCa r o m ), 55.11 (1 C, CH3 OCa r o m ), 52.4 (1 C, were synthesised following the general procedure, using gold cata-
C=CHCOCH3), 52.0 (1 C, CHOBz), 24.6 (1 C, CHCHOBz), 9.7 lyst (13.3 mg, 17.2 μmol), compound 2c (80.8 mg, 338 μmol), and
(CH ) ppm. IR (thin film): ν = 2930, 2831, 1722, 1510, 1267, 1246,
vinyl acetate (93.6 mg, 1.09 mmol), at –40 °C for 15 min. The prod-
˜
2
1736
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 1727–1740

Gold(I)-Catalysed Tandem Cyclisation
ucts were purified using an eluent system of 1:30 EtOAc/pentane
to give cis-9 (33.8 mg, 45%) and trans-9 (24.5 mg, 32%) as pale
yellow waxes.
(neat): ν = 2934, 1721, 1651, 1489, 1266, 1090, 1014, 710 cm–1.
˜
HRMS (EI): calcd. for C29H26O4Cl2 [M]+ 508.1203; found
508.1203.
Data for cis-9: Rf = 0.31 (1:10 EtOAc/pentane). 1H NMR
(400 MHz, CDCl3): δ = 7.29–7.23 (m, 6 H, CHarom), 7.20–7.17 (m,
2 H, CHarom), 4.81–4.80 (m, 1 H, C=CH), 4.38 (br. s, 1 H, C=CH),
4.05–4.01 (m, 1 H, CHOAc), 4.02 (br. s, 1 H, C=CHCH), 3.69 (s,
3 H, =COCH3), 3.03 (s, 3 H, C=CHCOCH3), 2.08 (s, 3 H, OC-
OCH3), 0.90–0.79 (m, 2 H, CH2), 0.39–0.33 (m, 1 H, AcOCHCH)
ppm. 13C NMR (400 MHz, CDCl3): δ = 171.0 (1 C, OC=O), 159.6
(1 C, CH=COCH3), 139.5 (1 C, CaromCHC=), 135.9 (1 C,
CaromCHCHC=), 132.8 (1 C, CaromCl), 132.2 (1 C, CaromCl), 130.9
(2 C, CHarom), 130.7 (2 C, CHarom), 128.2 (2 C, CHarom), 127.9 (2
C, CHarom), 99.6 (1 C, C=CH), 86.6 (1 C, =CHCOCH3), 59.8 (1
C, C=CHCH), 56.8 (1 C, =COCH3), 53.1 (1 C, CHOAc), 52.5 (1
C, C=CHCH), 51.9 (1 C, =CHCOCH3), 21.5 (1 C, CHCHOAc),
1
Data for trans-10: Rf = 0.27 (10:2 pentane/diethyl ether). H NMR
(400 MHz, CDCl3): δ = 8.00 (d, J = 7.2 Hz, 2 H, CHo-OBz), 7.57
(t, J = 7.4 Hz, 1 H, CHp-OBz), 7.42 (t, J = 7.6 Hz, 2 H, CHm-OBz),
7.27–7.26 (m, 2 H, CHarom), 7.25–7.24 (m, 2 H, CHarom), 7.24–7.23
(m, 2 H, CHarom), 7.22–7.20 (m, 2 H, CHarom), 4.68 (dt, J = 7.2,
4.2 Hz, 1 H, CHOBz), 4.49 (t, J = 1.9 Hz, 1 H, C=CH), 4.29 (d, J
= 1.2 Hz, 1 H, =CCH), 4.03 (s, 1 H, =CCHCH), 3.20 (s, 3 H,
=COCH3), 2.50 (s, 3 H, =CHCOCH3), 1.59–1.55 (m, 1 H, CH2),
1.55–1.53 (m, 1 H, BzOCHCH), 1.32–1.27 (m, 1 H, CH2) ppm. 13
C
NMR (400 MHz, CDCl3): δ = 167.2 (1 C, OC=O), 158.8 (1 C,
C H = C O C H 3 ) , 1 3 9 . 7 ( 1 C, Ca r o m C H C = ) , 1 3 6 . 3 ( 1 C,
CaromCHCHC=), 133.3 (1 C, CHp-OBz), 132.6 (1 C, CaromCl), 132.0
(1 C, CaromCl), 131.9 (2 C, CHarom), 130.9 (2 C, CHarom), 129.6 (2
C, CHo-OBz), 129.4 (1 C, OCOCarom), 128.5 (2 C, CHm-OBz), 128.0
(2 C, CHarom), 127.6 (2 C, CHarom), 97.3 (1 C, C=CH), 84.7 (1 C,
=CHCOCH3), 58.6 (1 C, =CCHCH), 56.2 (1 C, =COCH3), 55.9 (1
C, =CCHCH), 52.5 (1 C, =CHCOCH3), 51.9 (1 C, CHOBz), 24.7
21.2 (1 C, OCOCH ), 9.1 (1 C, CH ) ppm. IR (neat): ν = 2934,
˜
3
2
1743, 1652, 1489, 1225, 1090, 1014, 907, 730 cm–1. HRMS (EI):
calcd. for C24H24O4Cl2 [M]+ 446.1046; found 446.1043.
Data for trans-9: Rf = 0.20 (1:10 EtOAc/pentane). 1H NMR
(400 MHz, CDCl3): δ = 7.29–7.24 (m, 6 H, CHarom), 7.21–7.19 (m,
2 H, CHarom), 4.61 (t, J = 1.8 Hz, 1 H, C=CH), 4.44 (dt, J = 7.3,
4.1 Hz, 1 H, CHOAc), 4.12 (d, J = 1.0 Hz, 1 H, C=CH), 3.96 (br.
s, 1 H, C=CHCH), 3.59 (s, 3 H, =COCH3), 2.50 (s, 3 H,
=CHCOCH3), 2.09 (s, 3 H, OCOCH3), 1.39 (m, 1 H, AcOCHCH),
1.31 (m, 1 H, AcOCHCH2), 1.15 (td, J = 9.6, 7.3 Hz, 1 H, Ac-
OCHCH2) ppm. 13C NMR (400 MHz, CDCl3): δ = 171.5 (1 C,
OC=O), 159.1 (1 C, CH=COCH3), 139.6 (1 C, CaromCHC=), 136.2
(1 C, CaromCHCHC=), 132.6 (1 C, CaromCl), 132.1 (1 C, CaromCl),
131.9 (2 C, CHarom), 131.0 (2 C, CHarom), 128.0 (2 C, CHarom),
127.6 (2 C, CHarom), 97.2 (1 C, C=CH), 84.8 (1 C, =CHCOCH3),
57.4 (1 C, =CCHCH), 56.7 (=COCH3), 56.6 (1 C, =CCHCH), 52.4
(1 C, =CHCOCH3), 51.8 (1 C, CHOAc), 24.2 (1 C, CHCHOAc),
(1 C, CHCHOBz), 9.7 (1 C, CH ) ppm. IR (thin film): ν = 2933,
˜
2
1722, 1661, 1489, 1264, 1089, 1014, 709 cm–1. HRMS (EI): calcd.
for C29H26O4Cl2 [M]+ 508.1203; found 508.1202.
cis-/trans-2-[4,5-Bis(4-chlorophenyl)-1,3-dimethoxycyclopent-2-en-1-
yl]-1-methylcyclopropyl Acetate (cis-/trans-11): Compounds cis-11
and trans-11 were synthesised following the general procedure,
using gold catalyst (13.4 mg, 0.02 mmol), compound 2c (80.0 mg,
0.33 mmol), and isopropenyl acetate (64.8 mg, 0.65 mmol). The re-
action mixture was stirred at room temperature for 16 min. An iso-
cratic eluent of 1:30 Et2O/pentane was used to isolate a mixture of
cis-11 and trans-11 (32.5 mg, 42%). A small amount of cis-11 was
isolated from the isomeric mixture as a yellow oil (8.1 mg, 11%).
Due to the complexity of the 1H and 13C NMR spectra of the
isomeric mixture, the chemical shifts of trans-11 could not be as-
signed (overall cis/trans ratio 73:27). trans-11: Rf = 0.32 (10:3 pent-
ane/diethyl ether). Data for cis-11: Rf = 0.26 (10:3 pentane/diethyl
ether). 1H NMR (400 MHz, CDCl3): δ = 7.31–7.30 (m, 2 H,
CHarom), 7.27–7.26 (m, 2 H, CHarom), 7.26–7.24 (m, 2 H, CHarom),
7.24–7.22 (m, 2 H, CHarom), 4.88 (dd, J = 1.8, 1.1 Hz, 1 H, C=CH),
4.28 (s, 1 H, C=CHCH), 4.05 (s, 1 H, C=CHCH), 3.70 (s, 3 H,
C=COCH3), 3.11 (s, 3 H, C=CHCOCH3), 2.03 (s, 3 H, OCOCH3),
1.14–1.18 (m, 2 H, CH2), 1.05 (s, 3 H, CHCCH3), 0.28 (dd, J =
10.0, 7.8 Hz, 1 H, AcOCCH) ppm. 13C NMR (400 MHz, CDCl3):
δ = 170.2 (1 C, OC=O), 160.7 (1 C, CH=COCH3), 139.0 (1 C,
CaromCHCHC=), 136.6 (1 C, CaromCHC=), 132.8 (1 C, CaromCl),
132.2 (1 C, CaromCl), 131.0 (2 C, CHarom), 130.2 (2 C, CHarom),
128.4 (2 C, CHarom), 127.9 (2 C, CHarom), 98.5 (1 C, C=CH), 86.2
(1 C, C=CHCOCH3), 58.8 (1 C, COAc), 58.3 (1 C, C=CH), 57.0
( 1 C, C = C O C H 3 ) , 5 4 . 6 ( 1 C, C = C H C H ) , 5 2 . 0 ( 1 C,
C=CHCOCH3), 29.4 (1 C, CHCOAc), 22.6 (1 C, CHCCH3), 21.6
(1 C, OCOCH3), 16.7 (1 C, CH2) ppm. Data for a mixture of cis-
20.8 (1 C, OCOCH ), 9.3 (1 C, CH ) ppm. IR (neat): ν = 2933,
˜
3
2
1744, 1662, 1489, 1223, 1090, 1014, 908, 730 cm–1. HRMS (EI):
calcd. for C24H24O4Cl2 [M]+ 446.1046; found 446.1050.
cis-/trans-2-[4,5-Bis(4-chlorophenyl)-1,3-dimethoxycyclopent-2-en-1-
yl]cyclopropyl Benzoate (cis-/trans-10): Compounds cis-10 and
trans-10 were synthesised following the general procedure, using
gold catalyst (13.0 mg, 16.8 μmol), compound 2c (80.5 mg,
337 μmol), and vinyl benzoate (157.2 mg, 1.06 mmol), at –40 °C for
15 min. The products were purified using an eluent system of 1:50–
1:9 Et2O/pentane, followed by a second purification using 1:10
Et2O/pentane to give cis-10 (33.1 mg, 39%) as a colourless solid
and trans-10 (28.2 mg, 33%) as a pale yellow oil.
Data for cis-10: Rf = 0.35 (10:2 pentane/diethyl ether), m.p. 174–
1
177 °C. H NMR (400 MHz, CDCl3): δ = 8.02 (m, 2 H, CHo-OBz),
7.62–7.58 (m, 1 H, CHp-OBz), 7.49–7.44 (m, 2 H, CHm-OBz), 7.30–
7.20 (m, 8 H, CHarom), 4.91–4.90 (m, 1 H, C=CH), 4.37 (br. s, 1
H, =CCH), 4.15 (td, J = 7.1, 4.2 Hz, 1 H, CHOBz), 4.09 (d, J =
1.3 Hz, 1 H, =CCHCH), 3.71 (s, 3 H, =COCH3), 3.12 (s, 3 H,
=CHCOCH3), 1.09 (ddd, J = 8.2, 6.5, 4.3 Hz, 1 H, CH2), 0.96 (dt,
J = 9.9, 7.0 Hz, 1 H, CH2), 0.53 (ddd, J = 10.0, 8.2, 7.2 Hz, 1 H,
BzOCHCH) ppm. 13C NMR (400 MHz, CDCl3): δ = 167.1 (1 C,
11 and trans-11: IR (thin film): ν = 2935, 1744, 1653, 1489, 1207,
˜
1089, 1014, 908, 729 cm–1. HRMS (EI): calcd. for C25H26O4Cl2
[M]+ 460.1203; found 460.1205.
OC=O), 159.9 (1 C, CH=COCH3), 139.0 (1 C, CaromCHCHC=), trans-2-[4,5-Bis(4-chlorophenyl)-1,3-dimethoxycyclopent-2-en-1-yl]-
136.0 (1 C, CaromCHC=), 133.2 (1 C, CHp-OBz), 132.9 (1 C, 1-methylcyclopropyl Acetate (trans-12): Compound trans-12 was
CaromCl), 132.2 (1 C, CaromCl), 130.8 (2 C, CHarom), 130.4 (2 C, synthesised following the general procedure, using gold catalyst
CHarom), 130.1 (1 C, OCOCarom), 129.5 (2 C, CHo-OBz), 128.5 (2 C, (9.8 mg, 12.7 μmol), compound 2c (59.8 mg, 251 μmol), and 1-
CHm-OBz), 128.4 (2 C, CHarom), 127.9 (2 C, CHarom), 99.3 (1 C,
phenylvinyl acetate (130.6 mg, 0.805 mmol), at –40 °C for 30 min,
C=CH), 86.2 (1 C, =CHCOCH3), 59.4 (1 C, =CCHCH), 56.9 then 0 °C for 15 min. An isocratic eluent of 1:20 EtOAc/pentane
(=COCH3), 53.5 (1 C, CHOBz), 53.4 (1 C, =CCHCH), 52.0 (1 C, was used to isolate compound trans-12 (11.2 mg, 17%), and an
=CHCOCH3), 22.5 (1 C, CHCHOBz), 9.04 (1 C, CH2) ppm. IR
impure mixture of cis-12 and compound 1c that could not be fully
Eur. J. Org. Chem. 2014, 1727–1740
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1737

H.-S. M. Siah, M. Kaur, N. Iqbal, A. Fiksdahl
FULL PAPER
characterised. The amount of the cis-isomer was estimated from
C, C=CHCOCH3), 51.4 (1 C, CHOAc), 24.3 (1 C, CHCHOAc),
the NMR spectrum to be 11.8 mg, 18%.
20.7 (1 C, OCOCH ), 9.3 (1 C, CH ) ppm. IR (thin film): ν = 2940,
˜
3 2
2826, 1744, 1515, 1344, 1224, 1090, 1014, 728 cm–1. HRMS (EI):
calcd. for C24H24NO6Cl [M]+ 457.1292; found 457.1290.
Data for trans-12: Rf = 0.21 (1:20 EtOAc/pentane). 1H NMR
(400 MHz, CDCl3): δ = 7.46–7.44 (m, 2 H, CHarom COAc), 7.37–
7.35 (m, 2 H, CH=CCHCCHCHarom), 7.33–7.32 (m, 2 H, cis-/trans-2-[1,3-Dimethoxy-4,5-bis(4-nitrophenyl)cyclopent-2-en-1-
CHm-Ph), 7.33–7.32 (m, 1 H, CHp-Ph), 7.25–7.24 (m, 2 H, CH= yl]cyclopropyl Acetate (cis-/trans-14): Gold catalyst (13.4 mg,
CCHCCHarom), 7.07–7.05 (m, 2 H, C=CHCCHCCHCHarom), 17.4 μmol) was dissolved in dry CH2Cl2 (1.5 mL) at room tempera-
6.40–6.38 (m, 2 H, C=CHCCHCCHarom), 4.60–4.59 (m, 1 H, ture under a nitrogen atmosphere. A solution of compound 2d
C=CH), 4.25 (br. s, 1 H, CH=CCH), 3.61 (s, 3 H, =COCH3), 3.29
(br. s, 1 H, CH=CCHCH), 3.02 (s, 3 H, C=CHCOCH3), 1.83–1.79
(84.9 mg, 341 μmol) and vinyl acetate (89.0 mg, 1.03 mmol) in dry
CH2Cl2 (1 mL) was added, and the flask was washed out with
(m, 1 H, CH2), 1.82 (s, 3 H, OCOCH3), 1.39–1.33 (m, 1 H, CH2Cl2 (2ϫ 0.5 mL). At 15, 30, and 60 min, further 2d (56.7, 56.6,
CHCOAc), 1.29–1.24 (m, 1 H, CH2) ppm. 13C NMR (400 MHz, and 315.1 mg, respectively) was added in CH2Cl2 (1 mL each time)
CDCl3): δ = 169.8 (1 C, OC=O), 159.9 (1 C, C=CH), 138.9 (1 (total amount of compound 2d used: 513.2 mg, 2.06 mmol). After
C, C=CHCCHCarom), 136.33 (1 C, CH=CCHCarom), 136.31 (1 C, 120 min, reaction was quenched with NEt3 (5 drops), then the mix-
CaromCOAc), 132.8 (1 C, CaromCl), 131.9 (1 C, CaromCl), 131.8 (2 ture was filtered through Celite, and the filtrate was concentrated
C, CH=CCHCCHarom), 130.5 (2 C, C=CHCCHCCHarom), 130.1 in vacuo. The residue was purified by flash chromatography using
(2 C, CHo-Ph), 128.3 (2 C, CH=CCHCCHCHarom), 128.0 (2 C, an eluent of CH2Cl2 to give a 58:42 mixture of compounds cis-14
CHm-Ph), 127.9 (1 C, CHp-Ph), 127.4 (2 C, C=CHCCHCCHCH), and trans-14 (343.1 mg, 62%).
98.7 (1 C, C=CH), 85.7 (1 C, C=CHC), 63.7 (1 C, COAc), 59.4 (1
Data for cis-14: Rf = 0.17 (CH2Cl2). Yellow oil. 1H NMR
C, C=CHCCH), 56.7 (1 C, =COCH3), 52.1 (1 C, C=CHCOCH3),
(400 MHz, CDCl3): δ = 8.203–8.200 (m, 2 H), 8.19–8.17 (m, 2 H),
51.9 (1 C, C=CHCCH), 29.8 (1 C, CHCOAc), 21.4 (1 C, OC-
7.50–7.48 (m, 2 H), 7.45–7.43 (m, 2 H), 4.89–4.88 (m, 1 H, C=CH),
OCH ), 16.0 (1 C, CH ) ppm. IR (thin film): ν = 2935, 2831, 1753,
˜
3
2
4.56 (br. s, 1 H, CH=CCH), 4.202–4.198 (m, 1 H, CH=CCHCH),
4.07–4.02 (m, 1 H, CHOAc), 3.74 (s, 3 H, =COCH3), 3.05 (s, 3
H, C=CHCOCH3), 0.94–0.83 (m, 2 H, CH2), 0.37–0.31 (m, 1 H,
1654, 1489, 1232, 1090, 1015, 732, 699 cm–1. HRMS (EI): calcd.
for C30H28O4Cl2 [M]+ 522.1365; found 522.1355.
cis-/trans-2-[4-(4-Chlorophenyl)-1,3-dimethoxy-5-(4-nitrophenyl)- CHCHOAc) ppm. 13C NMR (400 MHz, CDCl3): δ = 170.6 (1 C,
cyclopent-2-en-1-yl]cyclopropyl Acetate (cis-/trans-13): Compounds
cis-13 and trans-13 were synthesised following the general pro-
cedure, using gold catalyst (10.1 mg, 13.1 μmol), compound 2c
OC=O), 159.6 (1 C, C=CH), 148.7 (1 C, CH=CCHCarom), 147.1
(1 C, CaromNO2), 146.8 (1 C, CaromNO2), 145.1 (1 C, C=CH-
CCHCarom), 130.4 (2 C, CHaromCNO2), 130.1 (2 C, CHaromCNO2),
(67.2 mg, 282 μmol), and compound 3e (see below; 70.3 mg, 123.2 (2 C, CHaromCHCNO2), 123.0 (2 C, CHaromCHCNO2), 99.3
254 μmol), at –40 °C for 30 min. The product was purified using
an eluent system of CH2Cl2 to give compounds cis-13 (51.7 mg,
45%) and trans-13 (37.1 mg, 32%) as pale yellow oil-foams.
(1 C, C=CH), 87.1 (1 C, C=CHC), 60.3 (1 C, CH=CCH), 57.0 (1
C, =COCH3), 53.2 (1 C, C=CHCCH), 52.8 (1 C, CHOBz), 52.1 (1
C, C=CHC), 21.3 (1 C, CHCHOBz), 21.2 (1 C, OCOCH3), 9.1 (1
C, CH ) ppm. IR (thin film): ν = 2940, 2842, 1740, 1657, 1517,
˜
2
Data for cis-13: Rf = 0.17 (CH2Cl2). 1H NMR (400 MHz, CDCl3):
δ = 8.18–8.15 (m, 2 H, CHaromCNO2), 7.49–7.47 (m, 2 H,
CHaromCHCNO2), 7.31–7.29 (m, 2 H, CHaromCCl), 7.21–7.19 (m,
1344, 1228, 906, 727, 648 cm–1. HRMS (EI): calcd. for C24H24N2O8
[M]+ 468.1533; found 468.1533.
2 H, CHaromCHCCl), 4.84–4.83 (m, 1 H, C=CH), 4.40 (br. s, 1 Data for trans-14: Rf = 0.21 (CH2Cl2). Pale yellow foam-solid, m.p.
1
H, CH=CCH), 4.16 (br. s, 1 H, C=CHCCH), 4.05–4.00 (m, 1 H,
CHOAc), 3.72 (s, 3 H, =COCH3), 3.07 (s, 3 H, C=CHCOCH3),
2.09 (s, 3 H, OCOCH3), 0.88–0.84 (m, 2 H, CH2), 0.46–0.40 (m, 1
H, CHCHOAc) ppm. 13C NMR (400 MHz, CDCl3): δ = 170.8 (1
C, OC=O), 160.5 (1 C, C=CH), 149.2, 146.7, 135.6, 133.0, 130.8
214–216 °C. H NMR (400 MHz, CDCl3): δ = 8.18–8.17 (m, 2 H,
CHaromCNO2), 8.16–8.15 (m, 2 H, CHaromCNO2), 7.52–7.50 (m, 2
H, CHaromCHCNO2), 7.44–7.43 (m, 2 H, CHaromCHCNO2), 4.71–
4.70 (m, 1 H, C=CH), 4.52–4.48 (m, 1 H, CHOAc), 4.33 (br. s, 1
H, CH=CCH), 4.12 (br. s, 1 H, C=CHCCH), 3.63 (s, 3 H,
(2 C, CHaromCHCCl), 130.1 (2 C, CHaromCHCNO2), 128.3 (2 C, =COCH3), 2.46 (s, 3 H, C=CHCOCH3), 2.12 (s, 3 H, OCOCH3),
CHaromCCl), 122.9 (2 C, CHaromCNO2), 98.6 (1 C, C=CH), 86.7, 1.46–1.42 (m, 1 H, CHCHOAc), 1.39–1.33 (m, 1 H, CH2), 1.28–
59.4 (1 C, CH=CCH), 56.9 (1 C, =COCH3 ), 53.6 (1 C,
C=CHCCH), 52.8 (1 H, CHOAc), 52.0 (1 C, C=CHCOCH3), 21.4 (1 C, OC=O), 159.1 (1 C, C=CH), 148.8, 147.0, 146.8, 145.3, 131.3
1.22 (m, 1 H, CH2) ppm. 13C NMR (400 MHz, CDCl3): δ = 171.3
(1 C, CHCHOAc), 21.1 (1 C, OCOCH3), 9.1 (1 C, CH2) ppm. IR
(2 C, CHaromCNO2), 130.2 (2 C, CHaromCNO2), 122.9 (2 C,
CHaromCHCNO2), 122.8 (2 C, CHaromCHCNO2), 97.0, 85.5 (1 C,
C=CHC), 58.1 (1 C, CH=CCH), 56.87 (1 C, C=CHCCH), 56.86
(1 C, =COCH3), 52.5 (1 C, C=CHCOCH3), 51.6 (1 C, CHOBz),
24.3 (1 C, CHCHOBz), 20.7 (1 C, OCOCH3), 9.4 (1 C, CH2) ppm.
(thin film): ν = 2932, 2829, 1745, 1653, 1516, 1345, 1229, 1091,
˜
1015, 835, 729 cm–1. HRMS (EI): calcd. for C24H24NO6Cl [M]+
457.1292; found 457.1289.
Data for trans-13: Rf = 0.23 (CH2Cl2). 1H NMR (400 MHz,
CDCl3): δ = 8.16–8.14 (m, 2 H, CHaromCNO2), 7.51–7.49 (m, 2 H,
CHaromCHCNO2), 7.28–7.26 (m, 2 H, CHaromCCl), 7.21–7.19 (m,
2 H, CHaromCHCCl), 4.65–4.64 (m, 1 H, C=CH), 4.49–4.44 (m, 1
IR (thin film): ν = 2940, 2826, 1745, 1663, 1596, 1515, 1343, 1225,
˜
1108, 855, 734 cm–1. HRMS (EI): calcd. for C24H24N2O8 [M]+
468.1533; found 468.1528.
H, CHOAc), 4.29 (br. s, 1 H, CH=CCH), 3.98 (br. s, 1 H, Compound 14 could alternatively be prepared from propargyl
C=CHCCH), 3.62 (s, 3 H, =COCH3), 2.47 (s, 3 H, C=CHCOCH3), acetal 2d and compound 3e (see below). Gold catalyst (2.6 mg,
2.10 (s, 3 H, OCOCH3), 1.43–1.36 (m, 1 H, CH2), 1.43–1.36 (m, 1
3.4 μmol) was dissolved in CH2Cl2 (0.5 mL), and the solution was
H, CHCHOAc), 1.23–1.18 (m, 1 H, CH2) ppm. 13C NMR cooled to –40 °C. Compounds 2d (17.1 mg, 68.6 μmol) and 3e
(400 MHz, CDCl3): δ = 171.4 (1 C, OC=O), 159.8 (1 C, C=CH), (17.2 mg, 75.7 μmol) were dissolved in CH2Cl2 (1 mL), and this
149.3, 146.7, 135.8, 132.8, 131.8 (2 C, CHaromCHCCl), 130.2 (2 C, solution was added to the solution of the gold catalyst. The flask
CHa r o m CHCNO2 ), 128.0 (2 C, CHar om CCl), 122.6 (2 C, was washed out with further CH2Cl2 (1 mL). The reaction mixture
CHaromCNO2), 96.2 (1 C, C=CH), 85.0 (1 C, C=CHC), 58.2 (1 C, was stirred at –40 °C for 60 min, then at room temperature for
CH=CCH), 56.8 (1 C, =COCH3), 56.2 (1 C, C=CHCCH), 52.5 (1 60 min. The product was purified using an eluent system of 1:2
1738
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 1727–1740

Gold(I)-Catalysed Tandem Cyclisation
EtOAc/pentane to give a mixture (52:48) of compounds cis-14 and
trans-14 (21.0 mg, 65%) as a pale yellow oil.
= 7.0 Hz, 3 H, CH=CCHCHCH3), 0.93–0.87 (m, 2 H, CH2) ppm.
13C NMR (400 MHz, CDCl3): δ = 171.6 (1 C, OC=O), 161.3 (1 C,
C=CH), 96.5 (1 C, C=CH), 83.2 (1 C, C=CHC), 56.1 (1 C,
=COCH3), 52.7 (1 C, C=CHCOCH3), 52.3 (1 C, CHOAc), 47.8 (1
C, C=CHCCH), 42.5 (1 C, CH=CCH), 23.7 (1 C, CHCHOAc),
20.8 (1 C, OCOCH3), 17.4 (1 C, CH=CCHCH3), 14.6 (1 C,
The ratio of product 14 to intermediate 3e could be varied by alter-
ing the reaction conditions, depending on which compound was
to be obtained. For example, at –40 °C and the standard ratio of
compound 2d to vinyl acetate of 1:3, cis-14 (39%), trans-14 (19%),
and 3e (20%) were formed. When the ratio of compound 2d to
vinyl acetate was increased to 1:10 (see below), a higher yield of 3e
(40%) and lower yields of product 14 (cis-14: 19%, trans-14: 25%)
were obtained. At very low temperatures (–78 °C), only trace
amounts of the tandem product were observed (GLC); purification
gave compound 3e (16%).
C=CHCCHCH ), 9.0 (1 C, CH ) ppm. IR (thin film): ν = 2931,
˜
3
2
2829, 1745, 1228, 1058, 914, 732 cm–1. HRMS (EI): calcd. for
C12H19O2 [M – OAc]+ 195.1385; found 195.1383.
cis-2-(1,3-Dimethoxy-4,5-dimethylcyclopent-2-en-1-yl)cyclopropyl
Benzoate (cis-16): Compound cis-16 was synthesised following the
general procedure, using gold catalyst (21.0 mg, 2.72 μmol), com-
pound 3e (77.3 mg, 0.54 μmol), and vinyl benzoate (142.5 mg,
0.96 mmol), at 0 °C for 15 min, then 20 °C for 15 min. The product
was purified using an eluent system of 1:40 Et2O/pentane to give
compound cis-16 (7.8 mg, 5%) as a grey oil. Rf = 0.44 (3:10 Et2O/
cis-2-[(Z)-1-Methoxy-2-(4-nitrophenyl)vinyl]cyclopropyl Acetate
(3e): Compound 3e was synthesised following the general pro-
cedure, using gold catalyst (13.1 mg, 17.0 μmol), compound 2d
(84.6 mg, 340 μmol), and vinyl acetate (295.3 mg, 3.43 mmol), at
–40 °C for 15 min. The product was purified using an eluent system
of CH2Cl2 to give compound 3e (37.6 mg, 40%) as a bright yellow
oil, along with cis-14 (15.0 mg, 19%) and trans-14 (19.2 mg, 24%).
1
pentane). H NMR (400 MHz, CDCl3): δ = 8.00 (d, J = 7.1 Hz, 2
H, CHo-OBz), 7.55 (t, J = 7.4 Hz, 1 H, CHp-OBz), 7.43 (t, J = 7.5 Hz,
2 H, CHm-OBz), 4.51–4.47 (m, 1 H, CHOBz), 4.33 (d, J = 0.8 Hz,
1 H, C=CH), 3.57 (s, 3 H, =COCH3), 3.31 (s, 3 H, =CHCOCH3),
2.89–2.86 (m, 1 H, BzOCHCH), 1.26 (s, 1 H, =CCHCH), 1.18 (d,
J = 7.3 Hz, 3 H, CH3CHC=), 1.15–1.13 (m, 1 H, BzOCHCH2),
1.11 (s, 1 H, =CCHCH), 1.10–1.07 (m, 1 H, BzOCHCH2), 1.04 (d,
J = 7.0 Hz, 3 H, CH3CHCHC=) ppm. 13C NMR (400 MHz,
CDCl3): δ = 167.4 (1 C, OC=O), 160.9 (1 C, CH=COCH3), 132.9
(1 C, CHp-OBz), 130.2 (1 C, OCOCarom), 129.5 (2 C, CHo-OBz), 128.4
(1 C, CHp-OBz), 97.3 (1 C, C=CH), 84.3 (1 C, =CHCOCH3), 56.3
(1 C, =COCH3), 52.8 (1 C, CHOBz), 52.1 (1 C, =CHCOCH3), 45.
9 (1 C, CHCHOBz), 29.7 (1 C, =CCHCH), 20.1 (1 C, =CCHCH),
14.6 (1 C, CH3CHCHC=), 12.9 (1 C, CH3CHC=), 8.0 (1 C,
1
Data for 3e: Rf = 0.30 (CH2Cl2). H NMR (400 MHz, CDCl3): δ
= 8.13–8.11 (m, 2 H, CHaromCNO2), 7.69–7.67 (m, 2 H,
CHaromCC=), 5.47 (br. s, 1 H, =CH), 4.45–4.40 (m, 1 H, CHOAc),
3.92 (s, 3 H, OCH3), 2.00 (s, 3 H, OCOCH3), 1.22 (m, 1 H,
CHCHOAc), 1.38–1.33 (m, 1 H, CH2), 1.22–1.18 (m, 1 H, CH2)
ppm. 13C NMR (400 MHz, CDCl3): δ = 171.5 (1 C, OC=O), 156.4
(1 C, C=CH), 144.8 (1 C, CaromNO2), 143.2 (1 C, CaromCH=), 128.3
(2 C, CHaromCCH=), 123.6 (2 C, CHaromCNO2), 105.7 (1 C,
C=CH), 55.3 (1 C, OCH3), 52.6 (1 C, CHOAc), 20.8 (1 C, OC-
OCH3), 18.8 (1 C, CHCHOAc), 11.0 (1 C, CH2) ppm. IR (thin
film): ν = 2942, 2914, 2852, 1747, 1589, 1509, 1334, 1230, 1109,
˜
1073, 861 cm–1. HRMS (EI): calcd. for C14H16NO5 [M + H]+
278.1028; found 278.1026.
CH CHOBz) ppm. IR (thin film): ν = 2932, 1722, 1646, 1451, 1269,
˜
2
1090, 731, 710 cm–1. HRMS (ESI): calcd. for C19H24NaO4 [M +
Na]+ 339.1567; found 339.1572.
cis-/trans-2-(1,3-Dimethoxy-4,5-dimethylcyclopent-2-en-1-yl)cyclo-
propyl Acetate (cis-/trans-15): Compounds cis-15 and trans-15 were
synthesised following the general procedure, using gold catalyst
(20.2 mg, 26.2 μmol), compound 2e (76.3 mg, 537 μmol), and vinyl
acetate (149.2 mg, 1.73 mmol), at –40 °C for 90 min, then 0 °C for
30 min. The products were purified using an eluent system of 1:1
(1:20 Et2O/pentane)/CH2Cl2 to give compounds cis-15 (3.2 mg,
7%) and trans-15 (1.9 mg, 4%), and a 1:1 mixture of cis-15 and
trans-15 (1.9 mg, 4%), all as yellow oils.
cis-2-(1-Ethoxy-2-methylprop-1-en-1-yl)cyclopropyl Acetate (3f):
Compound 3f was synthesised following the general procedure,
using gold catalyst (16.9 mg, 0.02 mmol), compound 2f[9] (66.1 mg,
0.43 mmol), and vinyl acetate (74.1 mg, 0.86 mmol). The reaction
mixture was stirred at room temperature for 15 min. A gradient
eluent of diethyl ether in pentane was used for purification. At the
stage of 40:1 pentane/diethyl ether, 3f (9.3 mg, 6%) was isolated as
a colourless oil. Rf = 0.46 (3:10 diethyl ether/pentane). 1H NMR
(400 MHz, CDCl3): δ = 4.35 (dt, J = 3.9, 6.6 Hz, 1 H, CHOAc),
3.78–3.70 (m, 1 H, CH2CH3), 3.58–3.50 (m, 1 H, CH2CH3), 1.97
(s, 3 H, CO2CH3), 1.67 (m, 1 H, AcOCHCH), 1.62 [s, 3 H,
C=C(CH3)CH3], 1.62 [s, 3 H, C=C(CH3)CH3], 1.20 (t, J = 7.0 Hz,
3 H, CH2CH3), 1.11–1.06 (m, 1 H, AcOCHCH2), 1.02–0.98 (m, 1
H, AcOCHCH2) ppm. 13C NMR (400 MHz, CDCl3): δ = 171.9 (1
C, OC=O), 142.0 [1 C, (CH3)2C=C], 119.4 [1 C, (CH3)2C=C], 64.9
(1 C, CH2CH3), 52.5 (1 C, CHOAc), 20.9 (1 C, CO2CH3), 18.6 [1
C, C=C(CH3)2] 17.6 [1 C, C=C(CH3)2], 16.2 (1 C, CHCHOAc),
15.2 (1 C, CH2CH3), 9.7 (1 C, CH2CHOAc) ppm.
1
Data for cis-15: Rf = 0.18 [1:1 (1:20 EtOAc/pentane)/CH2Cl2]. H
NMR (400 MHz, CDCl3): δ = 4.30 (br. s, 1 H, C=CH), 4.26–4.21
(m, 1 H, CHOAc), 3.57 (s, 3 H, =COCH3 ), 3.30 (s, 3 H,
CHCOCH3), 2.91–2.85 (m, 1 H, CH=CCHCH), 2.77–2.72 (m, 1
H, CH=CCH), 2.04 (s, 3 H, OCOCH3), 1.09–1.03 (m, 1 H,
CHCHOAc), 1.14 (d, J = 7.4 Hz, 3 H, CH=CCHCH3), 0.99–0.94
(m, 2 H, CH2) ppm. 13C NMR (400 MHz, CDCl3): δ = 171.7 (1
C, OC=O), 160.7 (1 C, C=CH), 97.2 (1 C, C=CH), 84.4 (1 C,
C=CHC), 56.2 (1 C, =COCH3), 52.2 (1 C, CHOAc), 51.8 (1 C,
C=CHCOCH3), 45.8 (1 C, CH=CCH), 41.6 (1 C, CH=CCHCH),
21.1 (1 C, OCOCH3), 19.7 (1 C, CHCHOAc), 14.7 (1 C,
C=CHCCHCH3), 13.2 (1 C, CH=CCHCH3), 8.01 (1 C, CH2) ppm.
cis-(1,8a)-trans-(3a,8a)-2,5,8a-Trimethoxy-1-(4-methoxyphenyl)-
1,3a,8,8a-tetrahydrocyclopenta[a]indene (17): Gold catalyst (8.4 mg,
11 μmol) was dissolved in dry CH2Cl2 (1.5 mL), and the solution
was stirred under a nitrogen atmosphere at room temperature.
Compound 2b (50.9 mg, 217 μmol) was dissolved in dry CH2Cl2
(1.0 mL), and this solution was added added to the solution of the
IR (thin film): ν = 2931, 2834, 1746, 1648, 1228, 1093, 781 cm–1.
˜
HRMS (EI): calcd. for C12H19O2 [M – OAc]+ 195.1385; found
195.1384.
Data for trans-15: Rf = 0.25 [1:1 (1:20 EtOAc/pentane)/CH2Cl2].
1H NMR (400 MHz, CDCl3): δ = 4.31–4.27 (m, 1 H, CHOAc), gold catalyst. The flask was washed out with further dry CH2Cl2
4.31–4.27 (m, 1 H, C=CH), 3.56 (s, 3 H, =COCH3), 3.40 (s, 3 H,
C=CHCOCH3), 2.68–2.62 (m, 1 H, CH=CCH), 2.57–2.52 (m, 1
H, CH=CCHCH), 2.03 (s, 3 H, OCOCH3), 1.20–1.16 (m, 1 H,
(2ϫ 0.5 mL), and this was added to the mixture. The reaction was
quenched with NEt3 (5 drops), the mixture was filtered through
CeliteTM, and the filtrate was concentrated in vacuo. The residue
CHCHOAc), 1.88 (d, J = 7.0 Hz, 3 H, CH=CCHCH3), 1.03 (d, J was purified by flash chromatography (1:3 Et2O/pentane) to give
Eur. J. Org. Chem. 2014, 1727–1740
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1739

H.-S. M. Siah, M. Kaur, N. Iqbal, A. Fiksdahl
FULL PAPER
dimer 17 (3.6 mg, 5%) as a yellow oil. Rf = 0.3 (1:3 Et2O/pentane).
1H NMR (400 MHz, CDCl3): δ = 7.24–7.22 (m, 2 H, CHaromCH-
COMe), 7.13 (d, J = 8.2 Hz, 1 H, MeOCCHarom), 6.87 (d, J =
2.4 Hz, 2 H, CHaromCOMe), 6.83–6.82 (m, 1 H, CCHaromCOMe),
6.75 (dd, J = 2.4, 8.2 Hz, 1 H, CCCHaromCH), 4.63–4.61 (m, 1 H,
C=CH), 4.18 (br. s, 1 H=CHCH), 3.81 (s, 3 H, CCHCOCH3), 3.80
(s, 3 H, p-OCH3), 3.77 (br. s, 1 H, =CCH), 3.51 (s, 3 H, =COCH3),
3.44 (d, J = 16.6 Hz, 1 H, CH2), 3.06 (d, J = 16.8 Hz, 1 H, CH2),
2.86 (s, 3 H, =CCHCOCH3) ppm. 13C NMR (400 MHz, CDCl3):
δ = 160.1 (1 C, =C), 159.1 (1 C, CaromOMe), 158.5 (1 C, CCH-
CaromOMe), 145.9 (1 C, =CHCHCarom), 133.1 (1 C, CH2Carom),
130.6 (1 C, =CCHCarom), 130.1 (2 C, CHaromCHCOMe), 125.1 (1
C, CH2CCHarom), 113.6 (2 C, CHaromCOMe), 112.6 [1 C,
CHaromC(OMe)CHC], 109.6 (1 C, MeOCHaromC), 96.0 (1 C,
=CH), 93.9 (1 C, CH2COMe), 59.1 (1 C, =CCH), 57.4 (1 C,
=CHCH), 56.5 (1 C, =COCH3), 55.4 (1 C, CaromOCH3), 55.2 (1 C,
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Received: November 7, 2013
Supporting Information (see footnote on the first page of this arti-
1
cle): Copies of H and 13C NMR spectra.
Acknowledgments
The authors thank the Research Council of Norway for financial
support.
Published Online: January 23, 2014
1740
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Eur. J. Org. Chem. 2014, 1727–1740