Gold(I)-catalysed tandem cyclization of propargyl acetals and alkynes

Article abstract of DOI:10.1016/j.tet.2015.12.080

To expand the understanding of the chemistry of propargyl acetals, their gold(I) catalysed cycloaddition reactions with alkynes have been investigated. We hereby report a novel tandem reaction that allows the construction of a new type of polysubstituted

Full text of DOI:10.1016/j.tet.2015.12.080

Tetrahedron 72 (2016) 1058e1068
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Tetrahedron
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Gold(I)-catalysed tandem cyclization of propargyl acetals and
alkynes
*
Huey-San Melanie Siah, Morten Christian Hogsnes, Naseem Iqbal, Anne Fiksdahl
Department of Chemistry, Norwegian University of Science and Technology, Høgskoleringen 5, NO-7491 Trondheim, Norway
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 6 October 2015
Received in revised form 18 December 2015
Accepted 30 December 2015
Available online 9 January 2016
To expand the understanding of the chemistry of propargyl acetals, their gold(I) catalysed cycloaddition
reactions with alkynes have been investigated. We hereby report a novel tandem reaction that allows the
construction of a new type of polysubstituted and highly functionalised bicyclic pentalene compounds,
2,6a-dimethoxy-3a-methyl-1,4,5-triphenyl-1,3a,4,6a-tetrahydropentalenes, with four stereogenic
centres.
Pure diastereomers were successfully isolated in up to 51% yield from mixtures of diastereomeric
products (up to 60% total yield) and characterized individually by NMR spectroscopy. A plausible
mechanism for the formation of these novel tandem products, based on subsequent [2þ2] and [2þ3]
cycloadditions, is proposed for this gold(I) catalysed reaction.
Keywords:
Propargyl acetal
Gold(I) catalysis
Tandem cycloadditions
Alkyne
Ó 2016 Elsevier Ltd. All rights reserved.
Pentalene
1. Introduction
The Fiksdahl group has shown that propargyl acetals show
significantly higher reactivity than the corresponding esters
Gold-catalysed reactions of propargyl esters are widely reported
in the literature and their ability to undergo very different reaction
pathways has been systematically studied and reviewed.1aed The
gold catalysed activation process of propargyl esters by 1,2-acyloxy
migration has, in particular, been shown to be a versatile strategy
for the generation of vinyl gold carbene species (Scheme 1a).3,4c,i,v
Hence, the propargyl-gold approach represents an important sup-
plement to the conventional vinyl-metal carbenoids, generated in
situ by metal-catalysed diazo decomposition, for the preparation of
effective vinyl-carbene all-carbon 1,3-dipolar reactants. The effi-
ciency of propargyl esters as safe surrogates of diazo compounds
for gold catalysed cyclopropanation has been thoroughly stud-
ied.4aew Some applications of propargyl esters in [2þ2],5aeb
[3þ2],6aed [4þ2],7 [4þ3]8aed and [3þ3]9 cycloaddition reactions
have also been reported.
(Scheme 1a).2 Additionally, cycloaddition reactions of propargyl
acetals provide access to a rich chemistry, as the choice of reactants
gives rise to a diverse range of products. Hence, the propargyl ac-
etals follow different cyclization pathways in gold(I) catalysed cy-
cloadditions (Scheme 1aed).2,12e14 Terminal propargyl acetals were
studied, demonstrating that the presence of terminal EWGs10,11 are
not required for such substrates.
Propargyl esters and acetals have been shown to undergo Au(I)
triple-bond activation and, respectively, 1,2-acyloxy and 1,5-alkoxy
migrations (Scheme 1a,b). The migration-fragmentation processes
afford, respectively, the gold-allyl-cation/gold-carbenoid species I
(Scheme 1a) and the respective highly reactive complex II (Scheme
1b).3
These intermediates can be trapped with different reagents,
typically alkenes. We have shown how the chemoselectivity of the
cycloadditions and, hence, the structures of the resulting products
are controlled by the nature of the substrates. By changing from
propargylic esters to acetals, the reaction pathway switches from
cyclopropanation2 (Scheme 1a) to [2þ3] cycloaddition (Scheme
1b),12 while a study on gold(I) catalysed cycloadditions of prop-
argyl acetals with vinyl acetates, showed that such substrates fol-
low a new tandem cyclization pathway (Scheme 1c).13 The total
outcome of the latter reactions was the formation of the
cyclopropyl-cyclopentenyl tandem products V by two subsequent
cycloaddition reactions. Phenylpropargyl acetals were also shown
to undergo intermolecular [5þ2] cycloaddition with benzaldimine
In contrast to propargyl esters, studies on gold(I)-catalysed re-
actions of corresponding propargyl acetals are scarce. Gold(I)-
catalysed [3þ2] cycloaddition of propargyl acetals and aldehydes
is reported to afford 2,5-dihydrofurans,10 recently also in an enan-
tioselective manner.11 However, it was emphasized that a terminal
carboxylate EWG was essential for the reaction to take place.
* Corresponding author. Fax: þ47 735 50 877; e-mail address: anne.fiksdahl@
chem.ntnu.no (A. Fiksdahl).
http://dx.doi.org/10.1016/j.tet.2015.12.080
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

H.-S.M. Siah et al. / Tetrahedron 72 (2016) 1058e1068
1059
Scheme 1. Proposed mechanisms of gold(I)-catalysed propargyl cycloadditions.2,12e14
.
substrates in the presence of a gold(I) catalyst to afford benzo[c]
azepin-4-ol derivatives VI (Scheme 1d).14 As shown in Scheme
1bed, the alkyl vinyl ether groups, originating from the propargyl
acetal substrates, are incorporated in central intermediates. The
proposed mechanisms indicate how the activating and directing
effect of these structure moieties are essential for the different
chemoselective outcomes of these reactions of propargyl acetals.
The previous results demonstrate that gold-catalysed cycload-
ditions of propargyl acetals are attractive and valuable synthetic
tools. To expand the knowledge of the highly reactive propargyl
acetals, it was decided to investigate the potential of other multiple
bond substrates, such as alkynes, to undergo chemoselective cy-
cloaddition reactions (Scheme 1e). We herein report the results
from our study of gold(I)-catalysed cyclization reactions of prop-
argyl acetals and different alkynes to give rise to highly function-
alised pentalene tandem products through double cycloaddition.
prior experience and optimization of gold catalysed propargyl ac-
etal cycloadditions.2e4 The introductory studies of the reaction of
propargyl acetal 1b (1 equiv) and phenylpropyne 2a (3 equiv) in
dichloromethane readily gave complete conversion into a mixture
of products after 15 min at room temperature in the presence of
5 mol-% of gold(I) catalyst [Au{P(t-Bu)2(o-biphenyl)CH3CN}]-SbF6
(Table 1, entry 1). Structural studies utilising NMR spectroscopy and
MS spectrometry identified the major product of the reaction as the
tandem bicyclic 2,6a-dimethoxy-1,5-bis[4-methoxyphenyl]-3a-
methyl-4-phenyl-1,3a,4,6a-tetrahydropentalene compound 4b,
formed in a mixture of diastereomers, due to the formation of four
stereogenic centres. Since the bicyclic product 4b is constructed of
two acetal units and one alkyne unit (see Proposed mechanism and
Scheme 2 below), it would be relevant to test whether a decrease in
the amount of alkyne 2a (from originally 3 equiv above) would
favour the tandem reaction. However, reduction to 1 equiv of al-
kyne 2a only caused a decrease in isolated total yields of formed
diastereomers, dropping from 51% to 42% (Table 1, entry 1, foot-
notes [c], [d]), indicating that a large excess of alkyne is necessary
for the formation of these particular products.
2. Results and discussion
2.1. Optimization studies
A few other gold catalysts were additionally screened using GLC
analysis to ascertain if a change in catalyst affected the outcome of
the reaction. Related gold(I) catalytic systems to that used in entry
Results from a brief screening of reaction conditions are sum-
marised in Table 1. The initial reaction conditions were chosen from

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H.-S.M. Siah et al. / Tetrahedron 72 (2016) 1058e1068
Table 1
1, but lacking the acetonitrile ligand, were prepared in situ by
counterion exchange of the respective gold chloride salt (entries 2,
3). These gave a decrease in conversion at the same or lower rate,
but the target diastereomeric compounds 4b were always the
dominating products. As chloride counterion exchange with e.g.,
SbFꢀ6 or NTfꢀ2 is supposed to be crucial for the activity of the gold(I)
catalyst,12e14 no reaction took place with the gold(I) chloride salt, as
expected (entry 4). The less bulky triphenylphosphane-based
gold(I) catalysts (entries 5, 6) gave no conversion into the desired
product 4b. Consistent with earlier observations, the gold(III)
salt,12e14 PicAu[III]Cl2 (entry 7), gave poor conversion to the desired
products. No cycloaddition took place in the presence of the silver
salts AgSbF6 or AgNTf2, ruling out a possible silver salt catalysed
reaction (entries 8, 9).12,15
Optimization studies of gold(I)-catalysed tandem cyclization reactionsa
Entry
1
Gold catalyst
Time
Conversion [%]b
[Au[I]{P(t-Bu)2(o-biphenyl)CH3CN}]SbF6
15 min
95
(51% isol. yield)c
(42% isol. yield)d
2
3
4
5
6
7
8
9
[Au[I]{P(t-Bu)2(o-biphenyl)}]ClþAgSbF6
[Au[I]{P(t-Bu)2(o-biphenyl)}]ClþAgNTf2
[Au[I]{P(t-Bu)2(o-biphenyl)}]Cl
Au[I](PPh3)ClþAgSbF6
Au[I](PPh3)Cl
60 min
15 min
24 h
15 min
24 h
80
66
nc
nde
nc
The original reactions conditions (entry 1) were used in further
studies. However, reduced reaction temperature was later shown to
increase the reaction effectivity, as discussed below (Table 2, entries
6,7).
PicAu[III]Cl2
AgSbF6
AgNTf2
15 min
15 min
15 min
17
ndf
ndf
a
The reactions were performed with 1b (1 equiv) and 2a (3 equiv) in DCM
(approx. c¼150 mM) together with 5 mol-% catalyst at rt. The reactions were
allowed to stir for the required time before being quenched with NEt3.
2.2. Proposed mechanism
b
The reactions were analysed by GLC. The target compound 4b was the main
product.
c
Based on our previous studies on regioselective cycloadditions
of propargyl substrates, the formation of tandem product 4 is
proposed to take place via two cycloaddition reactions. The general
mechanism is shown for propargyl acetal 1 and alkyne 2a in
Scheme 2. Propargyl acetal 1 can both undergo a 1,5- and a 1,4-
alkoxy shift to generate intermediate gold(I) species 10 and 100. It
has previously been demonstrated that gold(I)-activated propargyl
Isolated total yield by reaction of 1b (1 equiv) and 2a (3 equiv).
Isolated total yield by reaction of 1b (1 equiv) and 2a (1 equiv).
Full conversion, but target product 4b was not detected.
Full conversion, but target product 4b was not detected; 1-methoxy-4-(1-
d
e
f
methoxyprop-2-yn-1-yl)benzene was observed as the main product.
Scheme 2. Proposed mechanism for gold(I)-catalysed tandem cyclization reaction of propargyl acetals 1 and alkyne 2a to afford the pentalene products 4.

H.-S.M. Siah et al. / Tetrahedron 72 (2016) 1058e1068
1061
Table 2
Gold(I)-catalysed tandem cyclization reactions of propargyl acetals 1 and alkynes 2a
Entry
Acetal
Alkyne
Temp
rt.
Product, yieldb
4 [total yield]c
4a (60)c
4-cis-cis-cis
4-cis-tr-tr
4-cis-cis-tr
4-cis-tr-cis
4-tr-tr-cis
1
1a
22
14
6
5
<5
2
3
4
5
1b
rt.
rt.
rt.
rt.
4b (51)
44
d
5
12
d
d
<1
6
<1
4
d
d
d
d
1c
4c (29)c
1dd
n.c.d
d
10e24e
d
d
1e,f,g,h
4e, f, g, hc (10e30)e
d
d
6
1b
0
ꢁC
4b (57)
51
6
d
d
d
7
8
1b
1b
ꢀ40 ꢁC
4b (57)
4b (14)
51
14
6
d
d
d
d
d
d
ꢀ78 ꢁC (3 h)
d
9
1b
1b
1b
1b
1b
2b
2c
2d, e, f, g
2h
2i
0
0
0
0
0
ꢁC
ꢁC
ꢁC
ꢁC
ꢁC
4if
14
15
d
d
d
<2
d
10
11
12
13
4j (52)
19
18
n.c.g
n.c.h
4k (32)
32
d
d
d
a
The reactions were performed at rt with propargyl acetal 1 (1 equiv) and alkyne 2 (3 equiv) in DCM (approx. c¼150 mM) together with 5 mol-% of gold catalyst. The
reactions were allowed to stir for 15 min. before being quenched with NEt3. Diastereomers were isolated by flash chromatography.
b
Isolated yields refer to chromatographically purified compounds from complex mixtures of diastereomers. These numbers represent the maximum possible yield as the
products may contain minor amounts of other diastereoisomers or impurities. However, where necessary, the yields have been adjusted for solvent content. See spectra in the
Supplementary data for more information.
c
Product 6 was isolated in up to 10% yield from reactions with substrates 1a, 1c, 1e and 1h.
d
1d afforded [2þ3] cycloaddition product 7 (15%).
e
The cis-cis-cis isomers of 4f (24%) and 4g (10%) were isolated as well as minor amounts of other diastereomers of 4feg.
f
The isolated products were impure and the suggested stereochemistry is based on 1H NMR. Several additional diastereomers and regioisomers seem to be produced.
g
Full conversion of acetal 1b in 1e24 h, mainly into propargyl alcohol (up to 10%) and dimer 8 (up to 15%). The alkynes 2deg were recovered and products 4 were not
observed.
h
The product was impure; several other formed products decomposed over time, even at low temperatures.
substrates exist in rapid equilibrium with gold complexes, such as
10 and 100, which can lead irreversibly to a range of stable
products.3,12
In this case, alkyne 2a is believed initially to undergo a gold(I)-
catalysed [2þ2] cycloaddition5a,b reaction (ii) with one unit of
propargyl acetal 1 in the allenic form 10, generated by a 1,5-methoxy
migration (i). The reaction would give rise to a cyclobutylidene
intermediate 30. We have previously identified12 similar
cyclobutylidene products from [2þ2] cycloaddition reactions of
propargyl acetal. Subsequent intramolecular rearrangement and
double proton shift (iii) are proposed to take place via the oxonium
ion to afford the less strained pentadienyl intermediate 300. Due to
the presence of an activating vinyl ether moiety in 300, an additional
[2þ3] cycloaddition (v) with the active gold(I)-carbenoid species 100
may take place. In this case, 100 is generated by a 1,4-alkoxy shift of
a second unit of propargyl acetal (iv). As observed in our former

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H.-S.M. Siah et al. / Tetrahedron 72 (2016) 1058e1068
tandem reaction of propargyl acetals (Scheme 1c),13 the vinylic
alkoxy group, which activates for the second cycloaddition, is the
key prerequisite of both steps in the present new tandem reaction,
as well.
single ring structure 7 (15%), analogous to the [2þ3] cycloaddition
products obtained from propargyl acetals with vinyl compounds
(Scheme 1b).12 This was attributed to the strongly withdrawing
nature of the nitro group that favours an unusual [2þ3] alkyne
cycloaddition with the electrophilic gold carbenoid II (Scheme 2b).
The less selective substrates (4a, 4c, 4e, 4g, entries 1,3,5; footnote
[c]) also promoted a second reaction pathway giving the different
tandem product 6. This product appeared to be the result of two
[2þ3] cycloaddition reactions, proceeding through an intermediate
corresponding to product 7 below (entry 4, footnote [d]).
A series of reactions at varying temperature were carried out on
the most promising substrate 1b (entries 6e8). At 0 ꢁC and ꢀ40 ꢁC,
both the selectivity (51% cis-cis-cis isomer) and the total yield of
product 4b increased (57%, entries 6,7). The reaction rate slowed
down significantly at ꢀ78 ꢁC, as only 14% conversion of 1b was
observed by GLC after 3 h (entry 8). It was decided to carry out the
further experiments with propargyl acetal at 0 ꢁC.
A deuterium-labelling experiment with propargyl acetal, d-1a,
deuterated in the terminal position, afforded the tandem product
d2-4a with full incorporation of two deuterium atoms. The 1H NMR
spectrum showed the absence of the signals for the two affected
vinylic protons. As shown in Scheme 2, where H* indicates the
specific incorporation of deuterium, the results of the experiment
were consistent with the proposed mechanism for the formation of
the tandem products by subsequent (ii) [2þ2] and (iv) [2þ3] cy-
cloadditions including (iii) rearrangement and proton shifts.
The reaction takes place with one unit of an alkyne substrate
(2a) and two units of propargyl acetals (1). Since the two propargyl
substrates undergo an initial gold(I) catalysed 1,5- and a 1,4-alkoxy
shift, respectively, both the allene derivative (10) and the allylic/
carbenoid gold(I) complex (100) are reactive intermediates in this
tandem cycloaddition reaction.
With these results in hand, variation of the alkyne (2bei, entries
9e13) was carried out. The reaction with the terminal alkyne 2b
with acetal 1b afforded product 4i-cis-cis-cis (14%, entry 9), but also
seemed to produce a mixture of several diastereomers and
regioisomers, showing that removal of the methyl group appears to
lower the selectivity of this reaction substantially, allowing for
many other pathways to be accessed. The 4-OMe-phenylalkyne
substrate 2c afforded similar total yield to the non-substituted 2a,
but poor selectivity was obtained (entry 10). The more electron-
deficient alkynes (2d,e,f,g entry 11) were unable to undergo a tan-
dem reactions. Products 4 were not observed, while the alkynes
2deg were recovered. However, full conversion of acetal 1b took
place in 1e24 h, mainly into propargyl alcohol, but also the prop-
argyl acetal tricyclic dimer 8 was generated. This is in accordance
with our previous3 observations for the electron-rich p-OMe-phe-
nylpropargyl acetal 1b in other cycloaddition reactions. The for-
mation of dimer 8 has previously been proposed to take place by
a tandem dimerization reaction pathway, based on an intra-
molecular electrophilic aromatic substitution, activated by the p-
OMe-phenyl group, and a subsequent [2þ3] cycloaddition, acti-
vated by the vinyl ether moiety of the intermediate.3 Hence, the
competing formation of dimer 8, could be explained by insufficient
nucleophilicity of the second reactant, in the present case the al-
kynes 2deg (entry 11), to afford the desired tandem reaction. The
dialkylalkyne 2h (entry 12) showed poor ability to undergo tandem
reaction, while the ethyl-phenylalkyne 2i (entry 13) gave selec-
tively the 4k cis-cis-cis diastereomer (32%).
2.3. Reactivity
Applying the optimized reaction conditions (Table 1, entry 1),
the novel tandem transformation was further studied by modifying
the substrate(s), starting with the aryl propargyl moiety. The results
of the Au(I) catalysed reactions of propargyl acetals 1aed with
phenylpropyne 2a are presented in Table 2. All reactions were
allowed to stir for 15 min at room temperature before quenching
with triethylamine. TLC analysis showed full conversion after this
time and the propargyl acetals 1aec gave the expected tandem
cyclization products 4aec, obtained as diastereomeric mixtures
(Table 2, entries 1e3). As discussed below, NOESY 1H NMR exper-
iments were mainly used to propose the relative stereochemistry of
the diastereomers. The presence of a para-substituent on the aro-
matic propargyl acetals proved to affect both the reactivity and the
outcome of the tandem reactions. Unsubstituted phenyl propargyl
acetal 1a and alkyne 2a gave mostly the 4a-cis-cis-cis diastereomer
(22%) in addition to several other diastereomers (60% total yield,
entry 1). The presence of a strong electron-donating group (OMe) in
the para-phenyl position (1b) improved the selectivity in the tan-
dem reaction, as 44% out of the total yield of 51% represented the
4b-cis-cis-cis diastereomer (entry 2). In contrast, a halogen (Cl, 1c,
entry 3), gave reduced yield (29%) and selectivity. The nitro-
substituted phenylpropargyl substrate 1d failed to undergo tan-
dem reaction (entry 4). Due to the electron-deficient nature of the
substrate acetal 1d, the reaction with alkyne 2a afforded a different,
1H NMR spectra for each individual diastereomer of product 4
appeared to be quite characteristic. In particular, the distinguishing
Fig. 1. 1H NMR spectra for individual diastereomers of product 4, demonstrating the distinguishing shift value patterns for the CHaed protons.

H.-S.M. Siah et al. / Tetrahedron 72 (2016) 1058e1068
1063
shift value patterns for the CHa and CHb methines and the¼CHc
4. Experimental
4.1. General
and¼CHd vinylic protons, shown in Fig. 1aed, represented general
recognisable features for all the analogous cis-cis-cis, cis-trans-trans,
cis-cis-trans and cis-trans-cis diastereomers of products 4. As
demonstrated, quite large differences in shift values may be ob-
served for some proton-signals (e.g., Dd>1 ppm for CHa and CHd).
The identification and characterization of the different di-
astereomers of products 4 as well as for products 6 and 7 were
based on 2D NMR (HMBC/COSY, HSQC, NOESY). In particular,
NOESY 1H NMR experiments were essential in order to suggest the
relative stereochemistry of the four stereogenic centres in tandem
product 4. Designation of the stereochemistry was based on
a thorough comparative study of the observed NOESY correlations
with the groups of diastereomeric structures (based on 1H NMR
patterns above, Fig. 1aed). The conformational complexity and size
of the products allow a range of NOESY correlations to be obtained,
also between trans groups, as shown by models. Based on a variety
of combinations of NOESY correlations between the CHa and CHb
methines, the Me- and OMe-groups connected to the quaternary
carbons, we have proposed relative stereochemistry of the four
chiral centres in four isolated diastereomers (Fig. 1aed). Examples
of how the observed NOESY correlations indicated the designated
stereochemistry are shown in Fig. 2.
All reactions were performed under nitrogen atmosphere.
Commercial grade reagents were used as received. Dry solvents
were collected from a solvent purification system. All reactions were
monitored by GLC and thin-layer chromatography (TLC) using silica
gel 60 F254 (0.25 mm thickness). Flash chromatography was carried
out using silica gel 60 (0.040e0.063 mm). High Throughput Flash
Purification (HPFP) was performed on pre-packed cartridges.1H and
13C NMR spectra were recorded using a 300, 400 or 600 MHz
spectrometer. Chemical shifts are reported in ppm (d) downfield
from tetramethylsilane (TMS) as internal standard. Coupling con-
stants (J) are reported in Hertz (Hz). The attributions of the chemical
shifts were determined by means of COSY, HMQC, HMBC and NOESY
experiments. Melting points (mp) were determined using a Stuart
apparatus and are uncorrected. Accurate mass determination was
performed on a ‘Synapt G2-S’ Q-TOF instrument from Waters.
Samples were ionized with the use of ASAP probe, no chromatog-
raphy separation was used before the mass analysis. IR spectra were
obtained using a Smart Endurance reflection cell.
The generally low isolated yields can be explained by the close
chromatographic elution of the several produced diastereomers,
which gave overlapping zones both on TLC and flash chromatog-
raphy. This can be illustrated by e.g., the respective Rf values 0.19/
0.23/0.29 (1:10 EtOAc:pentane) of the three main isolated di-
astereomers of tandem product 4c. Due to challenging chromato-
graphic separation, the isolation of each diastereomer to the level
required for NMR characterization and identification of the par-
ticular diastereomers was demanding and loss of material during
purification was unavoidable. In addition, the stability of these
products was questionable. Thus, the real total amount of tandem
products formed in the most successful reactions could be more
than 60% of products 4a and 4b.
4.2. Preparation of the propargyl acetals
Propargyl acetals 1aed were generated as previously de-
scribed.3 1H and 13C NMR shifts were consistent with those in the
literature. Propargyl acetals 1eeh were generated following a sim-
ilar procedure:
4.2.1. 1-(1-((2-Methoxypropan-2-yl)oxy)prop-2-yn-1-yl)-4-(tri-
fluoromethyl)benzene (1e). 1-(4-(Trifluoromethyl)phenyl)prop-2-yn-
1-ol: A solution of ethynylmagnesium bromide (7.5 mL, 0.50 M in
THF, 3.8 mmol) was cooled to 0 ꢁC and a solution of 4-(tri-
fluoromethyl)benzaldehyde (0.40 mL, 2.9 mmol) in dry THF (3 mL)
was added slowly. The reaction mixture was stirred for 5 min at
that temperature, then the cooling bath was removed and the re-
action mixture was stirred at room temperature for 1 h. The re-
action was quenched by addition of 10 mL saturated aqueous
ammonium chloride and extracted with DCM (3ꢂ20 mL). The
combined organic layers were dried over Na2SO4, filtered and
concentrated in vacuo. The residue was purified by flash chroma-
tography (1:30 EtOAc:pentane) to yield 1-(4-(trifluoromethyl)
phenyl)prop-2-yn-1-ol as a bright yellow oil (451.3 mg, 77%).
3. Conclusions
In order to contribute to a better understanding of the chemistry
of propargyl acetals in the presence of gold(I), we have performed
a study on chemoselective gold(I)-catalysed cycloadditions of
propargyl acetals 1 with alkynes 2. We have shown that such
substrates undergo a new tandem cyclization pathway to readily
afford highly functionalised pentalene tandem products 4, obtained
as diastereomeric mixtures, from one unit of an alkyne substrate (2)
and two units of propargyl acetal (1). The proposed mechanism
involves a gold(I)-catalysed [2þ2] cycloaddition reaction with an
allene derivative. A subsequent rearrangement and a [2þ3] cyclo-
addition with an allylic gold(I) complex afford the tandem products
4. The allene and allyl intermediates are formed by respectively 1,5-
and 1,4-alkoxy shift of two propargyl substrates. Highest yield and
stereoselectivity was obtained with phenyl or 4-OMe-phenyl
propargyl acetal (1a or 1b) and phenylpropyne 2a at 0 ꢁC, affording
up to 51% yield of the pure 4-cis-cis-cis diastereomer.
Rf¼0.21 (1:30 EtOAc:pentane); 1H NMR (400 MHz, CDCl3)
d ppm
7.69e7.64 (m, 4H), 5.54 (d, J¼2.4 Hz,1H), 2.71(s,1H), 2.32 (dd, J¼2.4,
3.0 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d ppm 143.7, 130.7 (q,
J¼32.4 Hz), 126.8, 125.6 (q, J¼3.8 Hz), 124.0 (q, J¼270.4 Hz), 82.7,
75.5, 63.7; HRMS (EI) calcd for C10H6F3 [MeOH]þ 183.0422, obsd
183.0425.
A
mixture of 1-(4-(trifluoromethyl)phenyl)prop-2-yn-1-ol
(449.0 mg, 2.243 mmol) and 2-methoxypropene (5.0 mL,
52 mmol) was cooled to 0 ꢁC, then pyridinium p-toluenesulfonate
(PPTS, catalytic amount, <5 mg) was added. The cooling bath was
removed and the mixture stirred at room temperature for 1 h. The
mixture was diluted with DCM (50 mL), washed with water
(3ꢂ50 mL), then dried over anhydrous Na2SO4, filtered and con-
centrated in vacuo. The residue was purified by flash chromatog-
raphy (1:50 EtOAc:pentane) to yield 1-(1-((2-methoxypropan-2-yl)
oxy)prop-2-yn-1-yl)-4-(trifluoromethyl)benzene (1e) as
a pale
yellow oil (520.1 mg, 85%). Rf¼0.31 (1:30 EtOAc:pentane); 1H NMR
(400 MHz, CDCl3) d ppm 7.62 (s, 4H, H), 5.48 (s,1H, OCH), 3.18 (s, 3H,
OCH3), 2.56 (s, 1H, ^CH), 1.55 (s, 3H, CH3), 1.33 (s, 3H, CH3); 13C
NMR (100 MHz, CDCl3)
ppm 144.1,130.2 (q, J¼32.1 Hz),127.1,125.5
(q, J¼3.72 Hz), 124.0 (q, J¼270.4 Hz), 102.1, 83.7, 74.2, 61.9, 49.6,
25.3, 24.9; 13C NMR (376 MHz, CDCl3, C6F6 used as reference)
ppm
d
Fig. 2. Examples of NOESY correlations used to suggest stereochemistry of
diastereomers.
d

1064
H.-S.M. Siah et al. / Tetrahedron 72 (2016) 1058e1068
264.1; IR (neat, cmꢀ1) 3300, 2993, 2938, 2828, 1616, 1323, 1123,
1066, 1015, 848, 826; HRMS (EI) calcd for C14H15O2F3 [M]þ
272.1024, obsd 272.1019.
stirred at 0 ꢁC. PPTS (catalytic, <5 mg) was added and the mixture
stirred for 5 min. The mixture was allowed to come to ambient
temperature and stirred for 1 h. The mixture was diluted with DCM
(100 mL), washed with water (3ꢂ50 mL), the combined water
phase extracted with DCM (100 mL), then the combined organic
phase was dried over anhydrous Na2SO4, filtered and concentrated
in vacuo. The residue was purified by flash chromatography (1:10
EtOAc:pentane) to yield 1,3-dimethoxy-5-(1-((2-methoxypropan-
2-yl)oxy)prop-2-yn-1-yl)benzene (1g) as a colourless oil (640.4 mg,
84% over two steps). Rf¼0.09 (1:30 EtOAc:pentane); 1H NMR
4.2.2. 4-(1-((2-Methoxypropan-2-yl)oxy)prop-2-yn-1-yl)-N-methyl-
benzamide (1f). 4-(1-Hydroxyprop-2-yn-1-yl)-N-methylbenzamide:
A solution of ethynylmagnesium bromide (8.0 mL, 0.50 M in THF,
4.0 mmol) was cooled to 0 ꢁC and 4-formyl-N-methylbenzamide
(517.0 mg, 3.168 mmol) in dry THF (50 mL) was added slowly. The
reaction mixture was stirred for 5 min at that temperature, then the
cooling bath was removed and the reaction mixture was stirred at
room temperature for 2 h. Additional ethynylmagnesium bromide
(6.0 mL, 0.50 M in THF, 3.0 mmol) was added and the mixture
stirred for a further 30 min. Additional ethynylmagnesium bromide
(3.0 mL, 0.50 M in THF, 1.5 mmol) was added and the mixture
stirred for a further 30 min. Complete conversion was not obtained.
The reaction was quenched by addition of saturated aqueous am-
monium chloride (20 mL) and solvents were evaporated. The res-
idue was dissolved in DCM (100 mL) and water (50 mL) added. The
phases were separated and the water phase extracted with DCM
(2ꢂ50 mL). The combined organic layers were dried over Na2SO4,
filtered and concentrated in vacuo. The residue was purified by
flash chromatography (1:1 EtOAc:pentane) to yield 4-(1-
hydroxyprop-2-yn-1-yl)-N-methylbenzamide as a colourless oil
(263.7 mg, 44%). Rf¼0.13 (1:1 EtOAc:pentane). The product was
used directly without further analysis.
A mixture of 4-(1-hydroxyprop-2-yn-1-yl)-N-methylbenzamide
(263.7 mg, 1.394 mmol) and 2-methoxyprop-1-ene (5.0 mL,
52 mmol) were stirred at 0 ꢁC. PPTS (catalytic, <5 mg) was added
and the mixture stirred for 5 min. The mixture was allowed to come
to ambient temperature and stirred for 1 h. The mixture was diluted
with DCM (50 mL), washed with water (3ꢂ50 mL), the combined
water phase extracted with DCM (3ꢂ50 mL), then the combined
organic phase was dried over anhydrous Na2SO4, filtered and
concentrated in vacuo. The residue was purified by recrystallization
(DCM/pentane) to yield 4-(1-((2-methoxypropan-2-yl)oxy)prop-2-
(400 MHz, CDCl3)
d
ppm 6.66 (d, J¼2.2 Hz, 2H), 6.40 (t, J¼2.3 Hz,
1H), 5.36 (d, J¼2.2 Hz, OCH), 3.80 (s, 6H, 2ꢂArOCH3), 3.21 (s, 3H,
OCH3), 2.53 (d, J¼2.2 Hz, 1H, ^CH), 1.53 (s, 3H, CH3), 1.33 (s, 3H,
CH3); 13C NMR (100 MHz, CDCl3)
d ppm 160.8, 142.5, 104.8, 101.9,
99.9, 84.2, 73.6, 62.5, 55.4, 49.5, 25.3, 24.9; IR (neat, cmꢀ1) 3268,
2982, 2940, 2831, 1609, 1319, 1151, 1023, 864, 646; HRMS (EI) calcd
for C15H20O4 [MþH]þ 264.1362, obsd 264.1358.
4.2.4. 1,3,5-Trimethoxy-2-(1-((2-methoxypropan-2-yl)oxy)prop-2-
yn-1-yl)benzene (1h). 1-(2,4,6-Trimethoxyphenyl)prop-2-yn-1-ol: A
solution of ethynylmagnesium bromide (6.5 mL, 0.50 M in THF,
3.3 mmol) was cooled to 0 ꢁC. 2,4,6-Trimethoxybenzaldehyde
(505.3 mg, 2.575 mmol) in dry THF (15 mL) was added slowly.
The reaction mixture was stirred for 5 min at that temperature,
then the cooling bath was removed and the reaction mixture was
stirred at room temperature for 30 min. The reaction was
quenched by addition of saturated aqueous ammonium chloride
(20 mL), the phases separated and the water phase extracted with
DCM (3ꢂ20 mL). The combined organic layers were dried over
Na2SO4, filtered and concentrated in vacuo. The crude product of
1-(2,4,6-trimethoxyphenyl)prop-2-yn-1-ol (554.4 mg) was reac-
ted directly without further purification. Rf¼0.15 (1:4
EtOAc:pentane).
A mixture of the crude product of 1-(2,4,6-trimethoxyphenyl)
prop-2-yn-1-ol and 2-methoxyprop-1-ene (10.0 mL, 104 mmol)
were stirred at 0 ꢁC. PPTS (catalytic, <5 mg) was added and the
mixture stirred for 5 min. The mixture was allowed to come to
ambient temperature and stirred for 1 h. The mixture was diluted
with DCM (50 mL), washed with water (3ꢂ50 mL), the combined
water phase extracted with DCM (100 mL), then the combined
organic phase was dried over anhydrous Na2SO4, filtered and
concentrated in vacuo. The residue was purified by flash chro-
matography (1:4 EtOAc:pentane) to yield 1,3,5-trimethoxy-2-(1-
((2-methoxypropan-2-yl)oxy)prop-2-yn-1-yl)benzene (1h) as
a colourless oil (696.9 mg, 95% over two steps). Rf¼0.29 (1:4
yn-1-yl)-N-methylbenzamide (1f) as
a
colourless powder
(136.7 mg, 38%). Mp 127e129 ꢁC; Rf¼0.25 (1:1 EtOAc:pentane); 1H
NMR (400 MHz, CDCl3) d ppm 7.51e7.49 (m, 2H), 7.46e7.44 (m, 2H),
7.20 (br s, NH), 5.39 (s, 1H, OCH), 3.18 (s, 3H, OCH3), 2.54 (s, 1H,
^CH), 2.18 (s, 3H, NCH3), 1.54 (s, 3H, CH3), 1.32 (s, 3H, CH3); 13C
NMR (100 MHz, CDCl3) d ppm 168.2, 137.6, 136.2, 127.6, 119.8, 101.8,
84.3, 73.7, 62.1, 49.5, 25.4, 24.9, 24.6; IR (neat, cmꢀ1) 3299, 3184,
2987, 1668, 1608, 1549, 1319, 1014, 858, 668; HRMS (EI) calcd for
C
15H20NO3 [MþH]þ 262.1443, obsd 262.1440.
EtOAc:pentane); 1H NMR (600 MHz, CDCl3)
d ppm 6.13 (s, 2H),
4.2.3. 1,3-Dimethoxy-5-(1-((2-methoxypropan-2-yl)oxy)prop-2-yn-
1-yl)benzene (1g). 1-(3,5-Dimethoxyphenyl)prop-2-yn-1-ol: A solu-
tion of ethynylmagnesium bromide (8.0 mL, 0.50 M in THF,
6.05 (d, J¼2.4 Hz, 1H, OCH), 3.86 (s, 6H, 2ꢂArOCH3), 3.81 (s, 3H,
ArOCH3), 3.14 (s, 3H, OCH3), 2.36 (dd, J¼2.4, 0.66 Hz, 1H, ^CH),
1.48 (s, 3H, CH3), 1.26 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3)
4.0 mmol) was cooled to
0
ꢁC. 3,5-Dimethoxybenzaldehyde
d ppm 161.2, 110.1, 101.4, 91.3, 84.8, 70.1, 56.1, 55.3, 53.4, 49.0, 25.1,
(521.6 mg, 3.139 mmol) in dry THF (10 mL) was added slowly.
The reaction mixture was stirred for 5 min at that temperature,
then the cooling bath was removed and the reaction mixture was
stirred at room temperature for 1 h. The reaction was quenched by
addition of saturated aqueous ammonium chloride (10 mL), the
phases separated and the water phase extracted with DCM
(3ꢂ50 mL). The combined organic layers were dried over Na2SO4,
filtered and concentrated in vacuo. The crude product of 1-(3,5-
dimethoxyphenyl)prop-2-yn-1-ol (557.1 mg) was reacted directly
without further purification. Rf¼0.23 (1:4 EtOAc:pentane); 1H NMR
24.8; IR (neat, cmꢀ1) 3268, 3231, 2982, 2940, 1589, 1413, 1194,
1107, 967, 815; HRMS (EI) calcd for C16H22O5 [M]þ 294.1467, obsd
294.1470.
4.3. Preparation of alkynes
Alkynes 2a, 2b, 2f and 2h were purchased from Sigma Aldrich
and used as received. Alkynes 2c and 2d were synthesised through
base-induced methylation of their relevant terminal alkynes. Alkyne
2e was synthesised through copper-catalysed trifluoromethylation
of phenylacetylene. The dimeric alkyne 2g was synthesised through
Sonogashia self-cross-coupling of phenylacetylene.
(400 MHz, CDCl3)
d
ppm 6.72 (d, J¼2.1 Hz, 2H), 6.43 (t, J¼2.3 Hz,
1H), 5.40 (dd, J¼6.3, 2.2 Hz, 1H), 3.81 (s, 6H), 2.66 (d, J¼2.24 Hz, 1H),
2.18 (d, J¼6.2 Hz); 13C NMR (100 MHz, CDCl3)
d ppm 161.0, 142.3,
104.5, 100.6, 83.3, 74.8, 64.4, 55.4.
4.3.1. 1-Methoxy-4-(prop-1-yn-1-yl)benzene (2c). To a flame-dried
round-bottom flask under nitrogen was added 1-ethynyl-4-
methoxybenzene (520.9 mg, 3.941 mmol) in THF (20 mL). The
A mixture of the crude product of 1-(3,5-dimethoxyphenyl)
prop-2-yn-1-ol and 2-methoxyprop-1-ene (5.0 mL, 52 mmol) was

H.-S.M. Siah et al. / Tetrahedron 72 (2016) 1058e1068
1065
flask was placed in an ice-water/salt bath and allowed to cool. n-
Butyllithium (5.0 mL, 8.0 mmol) was added slowly and the reaction
was allowed to stir for 1 h. Iodomethane (0.50 mL, 8.0 mmol) was
added at that temperature and the reaction was stirred at room
temperature for 1 h. The reaction was quenched with saturated
solution of ammonium chloride (20 mL) and extracted with
dichloromethane. The organic phases were dried over MgSO4 and
the solvent removed in vacuo. The residue was purified by flash
chromatography (100% pentaned2% EtOAc/pentane) to give 1-
7 and 83 were isolated by flash chromatography using an appro-
priate eluent system.
4.4.1. 2,6a-Dimethoxy-3a-methyl-1,4,5-triphenyl-1,3a,4,6a-tetrahy-
dropentalene (4a) and 5,6a-dimethoxy-2-methyl-1,3,6-triphenyl-
1,3a,6,6a-tetrahydropentalene (6a). Compounds 4a and 6a were
synthesised according to the General Procedure at rt, using prop-
argylic acetal 1a (149.8 mg, 0.7334 mmol) and alkyne 2a (261.4 mg,
2.250 mmol). Flash chromatography (1:50 EtOAc:pentane) gave
products 4a and 6a as off-white or pale yellow oils.
methoxy-4-(prop-1-yn-1-yl)benzene (2c) as
a colourless oil
(194.5 mg, 34%). Rf¼0.16 (1:100 EtOAc:pentane); 1H NMR (300 MHz,
4a-cis-cis-cis (33.0 mg, 22%, mixture with two unknown iso-
CDCl3) d ppm 7.34e7.31 (m, 2H), 6.82e6.79 (m, 2H), 3.80 (s, 3H), 2.03
mers, yield calculated from 1H NMR): Rf¼0.44 (1:10 EtOAc:pen-
(s, 3H). 1H NMR shifts were consistent with those in the literature.16
tane); 1H NMR (600 MHz, CDCl3)
d ppm 7.15e7.02 (m, 15H), 5.40 (d,
J¼1.0 Hz, 1H, Hc), 5.34 (s, 1H, Hd), 4.15 (s, 1H, Ha), 3.54 (s,
4.3.2. 1-(Prop-1-yn-1-yl)-4-(trifluoromethyl)benzene (2d). Product
2d was generated using a similar procedure as that used for product
2c. 1H and 13C NMR shifts were consistent with those in the
literature.17
3H,¼COCH3), 3.42 (s, 1H, Hb), 3.01 (s, 3H, -COCH3), 1.03 (s, 3H, CH3);
13C NMR (150 MHz, CDCl3)
d ppm 128.1, 152.6, 138.5, 138.2, 136.3,
136.2, 129.4, 128.4, 128.2, 127.9, 127.6, 127.3, 127.0, 126.7, 109.6, 90.2,
69.9, 54.6, 51.2, 50.8, 49.4, 20.5; IR (thin film, cmꢀ1) 3018, 2925,
2821, 1644, 1492, 1453, 1096, 753, 701, 699; HRMS (EI) calcd for
4.3.3. (3,3,3-Trifluoroprop-1-yn-1-yl)benzene (2e). Under dry con-
ditions, copper(I) iodide (58.7 mg, 0.308 mmol), 1,10-
phenanthroline (108.7 mg, 0.6032 mmol) and potassium bi-
carbonate (295.4 mg, 2.951 mmol) were weighed into a Schlenk
flask and Togni’s reagent 1 (3,3-dimethyl-1-(trifluoromethyl)-1,2-
benziodoxole, 501.4 mg, 1.519 mmol) was added. Freshly distilled
DCM (5 mL) was added into this tube. Ethynylbenzene (158.1 mg,
1.548 mmol) in DCM (5 mL) was added to the tube over 6 h, using
a syringe pump. After addition, the reaction mixture was stirred for
another 18 h at room temperature. The reaction was quenched with
NH4Cl (10 mL) and water (10 mL) added. The aqueous phase was
extracted with DCM (3ꢂ20 mL) and the combined organic phases
were dried over anhydrous Na2SO4 and concentrated in vacuo
(moderate vacuum, approx. 500 mbar at rt, was used to avoid
product evaporation). The product was purified by flash chroma-
tography (pentane) to give (3,3,3-trifluoroprop-1-yn-1-yl)benzene
(2e) (92.5 mg, 35%) as a colourless oil. Rf¼0.67 (pentane); 1H NMR
C
29H28O2 [M]þ 408.2089, obsd 408.2085.
4a-cis-tr-tr (21.3 mg, 14%): Rf¼0.29 (1:10 EtOAc:pentane); 1H
NMR (400 MHz, CDCl3)
d ppm 7.61e7.13 (m, 10H), 6.98 (t, 1H,
J¼7.2 Hz), 6.90 (t, 2H, J¼8.0 Hz), 6.64 (s, 1H, Hd), 6.31 (d, 2H,
J¼7.2 Hz), 5.66 (s, 1H, Hc), 3.66 (s, 1H, Ha), 3.53 (s, 3H,¼COCH3), 3.52
(s, 1H, Hb), 3.16 (s, 3H,-COCH3), 0.99 (s, 3H, CH3); 13C NMR
(100 MHz, CDCl3) d ppm 156.8,142.0,138.7, 138.1, 138.0,136.1, 132.0,
128.2, 128.1, 127.8, 127.6, 127.4, 127.0, 126.7, 126.5, 105.3, 86.1, 72.3,
57.5, 57.2, 54.5, 51.2, 20.8; IR (thin film, cmꢀ1) 3012, 2952, 2925,
1646, 1490, 1453, 1231, 1096, 1032, 751; HRMS (EI) calcd for
C
29H28O2 [M]þ 408.2089, obsd 408.2087.
4a-cis-cis-tr (6%): Rf¼0.33 (1:10 EtOAc:pentane); 1H NMR
(400 MHz, CDCl3) d
ppm 7.09e6.95 (m, 15H), 6.26e6.25 (m, 1H, Hd),
5.72 (s, 1H, Hc), 4.70 (s, 1H, Ha), 3.62 (s, 1H, Hb), 3.59 (s, 3H,]
COCH3), 3.08 (s, 3H, ꢀCOCH3), 1.05 (d, 3H, J¼1.4 Hz, CH3); 13C NMR
(100 MHz, CDCl3)
d ppm 156.6, 139.7, 138.8, 138.3, 137.8, 135.4,
129.6, 128.8, 127.6, 127.2, 126.5, 125.9, 125.7, 106.3, 86.4, 71.5, 66.6,
54.4, 51.4, 51.3, 16.7; IR (thin film, cmꢀ1) 2987, 2955, 2925, 2587,
1490, 1454, 1376, 1183, 1147, 1068, 1013, 872; HRMS (EI) calcd for
(400 MHz, CDCl3)
d
ppm 7.54e7.49 (m, 2H), 7.48e7.46 (m, 1H),
ppm 132.4 (d,
7.41e7.37 (m, 2H); 13C NMR (100 MHz, CDCl3)
d
J¼1.2 Hz),130.9,128.6,118.5 (q, J¼1.9 Hz),114.9 (q, J¼256.6 Hz), 86.5
(q, J¼6.4 Hz), 75.7 (q, J¼53.0 Hz). 1H and 13C NMR shifts were
consistent with those in the literature.18
C
29H28O2 [M]þ 408.2089, obsd 408.2090.
4a-cis-tr-cis (5%): Rf¼0.33 (1:10 EtOAc:pentane); 1H NMR
(400 MHz, CDCl3) d
ppm 7.68e6.84 (m, 15H), 6.53 (m, 1H, Hd), 5.59
(s, 1H, Hc), 3.81 (s, 1H, Hb), 3.77 (s, 1H, Ha), 3.51 (s, 3H,]COCH3),
3.21 (s, 3H, ꢀCOCH3), 0.49 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3)
4.3.4. 1,4-Diphenylbuta-1,3-diyne (2g). In an open flask, copper(I)
iodide (77.0 mg, 0.404 mmol), potassium bicarbonate (410.4 mg,
4.099 mmol) were stirred in DCM (2 mL). Ethynylbenzene
(204.7 mg, 2.004 mmol) was dissolved in DCM (1 mL) and added to
the reaction mixture, then 1,10-phenanthroline (145.4 mg,
0.8069 mmol) and the reaction mixture was stirred for 24 h. Water
(25 mL) was added and the mixture was extracted with DCM
(3ꢂ25 mL). The combined organic phases were dried over Na2SO4,
filtered and concentrated in vacuo. The product was purified by
flash chromatography (pentane) to give 1,4-diphenylbuta-1,3-
diyne (2g) (92.2 mg, 46%) as a white crystalline solid. Rf¼0.30
d
ppm 156.6,142.1,140.5,139.5,137.6,128.2,127.9,127.6,127.1,127.0,
126.4, 106.2, 100.0, 87.1, 61.1, 54.8, 54.6, 54.6, 51.7, 20.8 (not possible
to assign all 13C shifts); IR (thin film, cmꢀ1) 2954, 2924, 2869, 2853,
1492, 1453, 1230, 1097, 699, 581, 570; HRMS (EI) calcd for C29H28O2
[M]þ 408.2089, obsd 408.2086.
6a (10.4 mg, 7%): Rf¼0.51 (1:10 EtOAc:pentane); 1H NMR
(600 MHz, CDCl3) d ppm 7.44e7.39 (m, 4H), 7.31e7.19 (m, 11H), 4.78
(dd, J¼2.1, 1.5 Hz, 1H), 4.34e4.34 (m, 1H), 4.09 (br s, 1H),
4.070e4.066 (m, 1H), 3.58 (s, 3H), 2.52 (s, 3H), 1.70 (d, J¼1.1 Hz); 13
C
NMR (150 MHz, CDCl3) d ppm 159.8, 138.9, 137.9, 137.7, 137.5, 135.7,
(pentane); 1H NMR (400 MHz, CDCl3)
d
ppm 7.56e7.54 (m, 2H),
ppm 132.5, 129.2,
130.2, 129.5, 128.23, 128.21, 127.9, 126.7, 126.6, 126.5, 95.9, 93.6,
66.6, 60.1, 57.1, 56.5, 54.7, 14.5; IR (thin film, cmꢀ1) 3049, 3023,
2925, 1695, 1494, 1452, 1104, 758, 731, 698; HRMS (EI) calcd for
7.40e7.36 (m, 3H); 13C NMR (100 MHz, CDCl3)
d
128.4, 121.7, 81.5, 73.9. 1H and 13C NMR shifts were consistent with
those in the literature.19
C
29H28O2 [M]þ 408.2089, obsd 408.2082.
4.4. General procedure for gold-catalysed reactions
4.4.2. 2,6a-Dimethoxy-1,5-bis(4-methoxyphenyl)-3a-methyl-4-
phenyl-1,3a,4,6a-tetrahydropentalene (4b). Compounds 4b were
synthesized according to the General Procedure at 0 ꢁC, using
propargylic acetal 1b (153.3 mg, 0.6543 mmol) and alkyne 2a
(223.0 mg, 2.250 mmol). Flash chromatography (1:20 EtOAc:pen-
tane) gave products 4b as pale yellow or yellow oils.
The relevant propargyl acetal 1aeh (1 equiv) and alkyne 2aeh
(3 equiv) were dissolved in dichloromethane (2e3.4 mL) and added
to a solution of the gold catalyst, Au[P(t-Bu)2(o-biphenyl)]SbF6
(5 mol-%), in dichloromethane (1.7e3 mL). The reaction was stirred
for 15 min at the required temperature. The reaction mixture was
filtered through Celite and concentrated in vacuo. The products 4, 6,
4b-cis-cis-cis (77.7 mg, 51%): Rf¼0.24 (1:10 EtOAc:pentane); 1H
NMR (400 MHz, CDCl3) d ppm 7.56e7.51 (m, 1H), 7.35e7.26 (m, 5H),

1066
H.-S.M. Siah et al. / Tetrahedron 72 (2016) 1058e1068
7.16e7.04 (m, 1H), 6.94 (d, 2H, J¼8.5 Hz), 6.77 (d, 4H, J¼8.7 Hz), 5.37
(s, 1H, Hc), 5.33 (s, 1H, Hd), 4.09 (s, 1H, Ha), 3.77 (s, 3H), 3.75 (s, 3H),
3.54 (s, 3H,]COCH3), 3.35 (s, 1H, Hb), 3.02 (s, 3H, ꢀCOCH3), 1.02 (s,
Hc), 3.71 (s, 1H, Hb), 3.69 (s,1H, Ha), 3.51 (s, 3H,]COCH3, overlapping
with 4c-cis-cis-tr), 3.18 (s, 3H, ꢀCOCH3), 0.48 (s, 3H, CH3); 13C NMR
(100 MHz, CDCl3) d ppm 156.6, 142.1, 140.5, 139.5, 137.6, 128.2, 127.9,
3H, CH3); 13C NMR (100 MHz, CDCl3)
d
ppm 158.3, 158.2, 158.2,
127.6, 127.1, 127.0, 126.4, 106.2, 100.0, 87.1, 61.1, 54.8, 54.6, 54.6, 51.7,
20.8 (not possible to assign all carbon shifts); IR (film, cmꢀ1) 2955,
2923, 2867, 1490, 1257, 1091, 1014, 817, 742, 703, 568; HRMS (EI)
calcd for C29H26O325Cl2 [M]þ 476.1310, obsd 476.1310.
152.6, 136.3, 130.3, 128.4, 128.2, 127.3, 127.0, 126.9, 113.2, 113.1,
109.6, 90.1, 69.0, 55.13, 55.08, 54.6, 51.1, 49.9, 49.4, 25.6, 20.5; IR
(film, cmꢀ1) 2919, 2824, 1644, 1610, 1509, 1243, 1177, 1124, 1034,
903, 826, 730, 699; HRMS (EI) calcd for C31H32O4 [M]þ 468.2301,
obsd 468.2299.
6c (7 mg, 7%): Rf¼0.58 (1:10 EtOAc:pentane); 1H NMR
(400 MHz, CDCl3)
d
ppm 7.41 (d, 4H, J¼4.3 Hz), 7.32e7.26 (m, 2H),
4b-cis-tr-tr (8.6 mg, 6%): Rf¼0.14 (1:10 EtOAc:pentane); 1H
7.26e7.23 (m, 2H), 7.17e7.11 (m, 5H), 4.78 (s, 1H), 4.32 (s, 1H), 4.03
NMR (400 MHz, CDCl3)
d
ppm 7.53e7.51 (m, 1H), 7.05e6.92 (m, 6H),
(s, 1H), 3.99 (s, 1H), 3.58 (s, 3H), 2.64 (s, 3H), 1.68 (s, 3H); 13C NMR
6.79e6.72 (m, 4H), 6.61 (s, 1H, Hd), 6.38 (d, 2H, J¼7.2 Hz), 5.63 (s,
(100 MHz, CDCl3) d ppm 159.3, 138.1, 137.1, 137.1, 136.2, 135.1, 132.5,
1H, Hc), 3.74 (s, 3H), 3.74 (s, 3H), 3.60 (s, 1H, Ha), 3.53 (s, 3H,]
131.4, 130.8, 128.3, 128.2, 128.2, 128.1, 127.8, 96.1, 93.1, 66.1, 59.5,
56.6, 56.0, 54.7, 14.4; IR (thin film, cmꢀ1) 2950, 2919, 1646, 1490,
1340, 1225, 1090, 1014, 701; HRMS (EI) calcd for C29H2635Cl2O2 [M]þ
477.1385, obsd 477.1388.
COCH3), 3.45 (s, 1H, Hb), 3.16 (s, 3H, ꢀCOCH3), 0.98 (s, 3H, CH3); 13
C
NMR (100 MHz, CDCl3) d ppm 158.8, 158.3, 156.8, 142.1, 138.0, 136.2,
132.9, 130.9, 130.2, 128.9, 127.6, 127.4, 126.5, 113.2, 105.3, 86.0, 71.4,
57.2, 56.6, 55.4, 55.1, 54.5, 51.2, 20.8; IR (cm-1) 2900, 2240, 1710,
1302, 1223, 905, 734; HRMS (EI) calcd for C31H32O4 [M]þ 468.2301,
obsd 468.2299.
4b-cis-cis-tr and 4-cis-tr-cis were isolated as a mixture (trace):
1H NMR of the mixture is supplied. Identification of the isomers
was carried out by comparison with the 4a analogue. The charac-
teristic 1H NMR signals are given below.
4.4.4. Products 4e and 6e were synthesized according to the General
Procedure at rt, using propargylic acetal 1e (150.3 mg, 0.5520 mmol)
and alkyne 2a (191.9 mg, 1.652 mmol). Flash chromatography (2:1
EtOAc:pentane) gave products 4e and 6e as a mixture of pale yellow
oils. This mixture was inseparable by flash chromatography and
appeared to contain both compounds of type 4e and 6e, but their
identity could not be determined conclusively. (1H NMR in
Supplementary data).
4b-cis-cis-tr: 1H NMR (400 MHz, CDCl3)
d
ppm 6.22 (s, 1H, Hd),
5.69 (s, 1H, Hc), 4.62 (s, 1H, Ha), 3.58 (s, 3H,]COCH3), 3.55 (s, 1H,
Hb), 3.08 (s, 3H, ꢀCOCH3), 1.09 (s, 3H, CH3).
4b-cis-tr-cis: 1H NMR (400 MHz, CDCl3)
d
ppm 6.50 (s, 1H, Hd),
4.4.5. 4,40-(2,6a-Dimethoxy-3a-methyl-4-phenyl-1,3a,4,6a-tetrahy-
dropentalene-1,5-diyl)bis(N-methylbenzamide) (4f). Compounds 4f
were synthesized according to the General Procedure at rt, using
propargylic acetal 1f (136.0 mg, 0.5204 mmol) and alkyne 2a
(181.0 mg,1.561 mmol). Flash chromatography (2:1 EtOAc:pentane)
gave products 4f as pale yellow or yellow oils.
5.56 (s, 1H, Hc), 3.81 (s, 1H, Hb), 3.72 (s, 1H, Ha), 3.51 (s, 3H,]
COCH3), 3.20 (s, 3H, ꢀCOCH3), 0.49 (s, 3H, CH3).
4.4.3. 1,5-Bis(4-chlorophenyl)-2,6a-dimethoxy-3a-methyl-4-phenyl-
1,3a,4,6a-tetrahydropentalene (4c) and 1,6-bis(4-chlorophenyl)-5,6a-
dimethoxy-2-methyl-3-phenyl-1,3a,6,6a-tetrahydropentalene
(6c). Compounds 4c and 6c were synthesized according to the
General Procedure at rt, using propargylic acetal 1c (110 mg,
0.461 mmol) and alkyne 2a (161 mg, 1.38 mmol). Flash chroma-
tography (1:100 EtOAc:pentane) gave the products 4c and 6c as off-
white oils.
4f-cis-cis-cis (32 mg, 24%): Rf¼0.29 (2:1 EtOAc:pentane); 1H
NMR (400 MHz, CDCl3) d ppm 7.57e7.50 (m, 2H), 7.47e7.43 (m, 2H),
7.39e7.32 (m, 4H), 7.18e7.05 (m, 3H), 6.97e6.95 (m, 2H), 5.37 (s,1H,
Hc), 5.32 (s, 1H, Hd), 4.10 (s, 1H, Ha), 3.52 (s, 3H,]COCH3), 3.36 (s,
1H, Hb), 3.00 (s, 3H, ꢀCOCH3), 2.10 (s, 6H),1.01 (s, 3H, CH3); 13C NMR
(100 MHz, CDCl3)
d ppm 168.3, 168.2, 157.9, 152.9, 136.6, 136.4,
4c-cis-tr-tr (12 mg, 12%): Rf¼0.19 (1:10 EtOAc:pentane); 1H
135.9, 134.0, 132.3, 129.9, 128.2, 127.4, 126.9, 126.5, 119.1, 109.6, 90.2,
NMR (400 MHz, CDCl3)
d
ppm 7.55e7.53 (m, 1H), 7.23e7.06 (m,
69.2, 60.4, 54.6, 51.1, 50.1, 49.4, 24.5, 24.4, 20.5; IR (thin film, cmꢀ1
)
6H), 7.06e7.03 (m, 2H), 6.98e9.95 (m, 2H), 6.63 (s, 1H, Hd),
6.39e6.37 (m, 2H), 5.64 (d, 1H, J¼1.1 Hz, Hc), 3.61 (s, 1H, Ha), 3.52
(s, 3H,]COCH3), 3.47 (s, 1H, Hb), 3.14 (s, 3H, ꢀCOCH3), 0.99 (s, 3H,
3304, 3049, 2925, 1669, 1601,1533, 1517, 1412, 1317, 768, 699; HRMS
(EI) calcd for C33H34N2O4 [M]þ 522.2519, obsd 522.2518.
4f-cis-tr-tr was isolated as a mixture (8 mg, 6%): 1H NMR of the
mixture is supplied. Identification of the isomers was carried out by
comparison with the 4a analogue. The characteristic 1H NMR sig-
nals are given below.
CH3); 13C NMR (100 MHz, CDCl3)
d ppm 156.4, 141.5, 138.1, 137.1,
136.4, 135.7, 133.2, 133.0, 132.6, 129.5, 128.2, 128.1, 127.6, 127.4,
126.9, 105.3, 85.9, 71.4, 57.0, 56.8, 54.5, 51.3, 20.9; IR (thin film,
cmꢀ1) 2919, 2839, 1639, 1490, 1445, 1226, 1091, 1014, 838, 813, 741,
702; HRMS (EI) calcd for C29H26O235Cl2 [M]þ 476.1310, obsd
476.1309.
4f-cis-tr-tr: 1H NMR (400 MHz, CDCl3)
d
ppm 6.62 (s, 1H, Hd),
5.63 (s, 1H, Hc), 3.62 (s, 1H, Ha), 3.51 (s, 3H,]COCH3), 3.47 (s, 1H,
Hb), 3.15 (s, 3H, ꢀCOCH3), 0.99 (s, 3H, CH3).
4c-cis-cis-tr (6.4 mg, 6%, isolated as a mixture with 4c-cis-tr-cis):
Rf¼0.23 (1:10 EtOAc:pentane); 1H NMR (400 MHz, CDCl3)
d
ppm
4.4.6. 1,5-Bis(3,5-dimethoxyphenyl)-2,6a-dimethoxy-3a-methyl-4-
phenyl-1,3a,4,6a-tetrahydropentalene (4g). Compound 4g was syn-
thesized according to the General Procedure at rt, using propargylic
acetal 1f (153.4 mg, 0.5804 mmol) and alkyne 2a (206.5 mg,
1.778 mmol). Flash chromatography (1:10 EtOAc:pentane) gave
products 4f as colourless oils.
7.51e7.49 (m, 1H), 7.37e7.35 (m, 3H), 7.18e7.16 (m, 1H), 7.06 (d, 4H,
J¼8.4 Hz), 7.02e7.00 (m, 2H), 6.88 (d, 2H, J¼8.6 Hz), 6.26e6.25 (m,
1H, Hd), 5.70 (s, 1H, Hc), 4.64 (s, 1H, Ha), 3.58 (s, 4H,]COCH3 and Hb,
overlapping), 3.07 (s, 3H, ꢀCOCH3), 1.09 (d, 3H, J¼1.3 Hz, CH3); 13C
NMR (100 MHz, CDCl3) d ppm 138.6, 106.3, 70.7, 54.5, 51.5, 50.8, 17.0
(not possible to assign all carbon shifts); IR (film, cmꢀ1) 2955, 2923,
4g-cis-cis-cis (14.8 mg, 10%): Rf¼0.22 (1:4 EtOAc:pentane); 1H
2867, 1490, 1257, 1091, 1014, 817, 742, 703, 568; HRMS (EI) calcd for
NMR (400 MHz, CDCl3) d ppm 7.32e7.26 (m, 5H), 6.86 (s, 1H), 6.37
C
29H28O235Cl2 [M]þ 476.1310, obsd 476.1309.
(s, 1H), 6.34 (s, 1H), 6.31 (s, 1H), 6.21 (s, 2H), 5.42 (s, 1H, Hc), 5.37 (s,
1H, Hd), 4.07 (s, 1H, Ha), 3.61 (s, 6H), 3.55 (s, 3H,]COCH3), 3.32 (s,
1H, Hb), 3.11 (s, 3H, ꢀCOCH3), 1.05 (s, 3H, CH3); 13C NMR was not
obtained due to impurity. Identification of the isomer was carried
out by comparison with the 4a analogue. HRMS (EI) calcd for
4c-cis-tr-cis (3.6 mg, 4%, isolated as a mixture with 4c-cis-cis-tr):
1H NMR of the mixture is supplied. Identification of the isomers was
carried out by comparison with the 4a analogue. The characteristic
1H and 13C NMR signals are given below. Rf¼0.29 (1:10 THF:pen-
tane); 1H NMR (400 MHz, CDCl3)
d
ppm 6.50 (m, 1H, Hd), 6.58 (s, 1H,
C
33H36O6 [M]þ 528.2512, obsd 528.2511.

H.-S.M. Siah et al. / Tetrahedron 72 (2016) 1058e1068
1067
4.4.7. 3a,5-Dimethoxy-2,4-bis(4-methoxyphenyl)-1-phenyl-
(m, 1H, CH2), 1.45e1.33 (m, 1H, CH2), 0.75 (t, J¼7.3 Hz, 3H, CH3); 13
C
1,3a,4,6a-tetrahydropentalene (4i). Compounds 4i were synthe-
sized according to the General Procedure at 0 ꢁC, using propargylic
acetal 1b (152.4 mg, 0.6505 mmol) and alkyne 2b (197.5 mg,
1.934 mmol). Flash chromatography (1:20 EtOAc:pentane) gave
mixtures of products 4i as pale yellow oils. One compound was
identified as the 4i-cis-cis-cis isomer, while another also seemed to
be a stereoisomer of 4, but did not correspond to any of the already
identified isomers. The minor amount did not to allow for charac-
terisation. 1H NMR of both compounds is provided.
NMR (100 MHz, CDCl3)
d
ppm 158.4,158.3,158.2,153.9,136.5,130.3,
130.2, 128.4, 128.2, 127.3, 127.2, 126.2, 113.0, 107.3, 90.8, 66.5, 55.1,
55.0, 54.6, 53.3, 51.9, 51.5, 24.5, 8.5; IR (thin film, cmꢀ1) 2962, 2930,
2826, 1704, 1610, 1510, 1244, 178, 1034, 809, 824, 729, 699; HRMS
(EI) calcd for C32H34O4 [M]þ 482.2457, obsd 482.2462.
4.4.10. 5,6a-Dimethoxy-2-methyl-3-phenyl-1,6-bis(2,4,6-
trimethoxyphenyl)-1,3a,6,6a-tetrahydropentalene (6h). The title
compound was synthesized according to the General Procedure at
rt, using propargylic acetal 1h (151.2 mg, 0.5137 mmol) and alkyne
2a (184.0 mg, 1.584 mmol). Flash chromatography (1:3 EtOAc:-
pentane) gave product 6h as a pale yellow oil (16.4 mg, 11%):
4i-cis-cis-cis (20.5 mg, 14%): Identification of the isomer was
carried out by comparison with the 4a analogue. The characteristic
1H signals are given below. HRMS (EI) calcd for C30H30O4 [M]þ
454.2144, obsd 454.2145.
Rf¼0.18 (1:3 EtOAc:pentane); 1H NMR (600 MHz, CDCl3)
d ppm
Not determined isomer of 4: 1H NMR (400 MHz, CDCl3)
d
ppm
7.41e7.39 (m, 2H), 7.37e7.35 (m, 2H), 7.23e7.20 (m, 1H), 6e11 (d,
J¼2.4 Hz, 1H), 6.10 (d, J¼2.4 Hz, 1H), 6.08 (d, J¼2.3 Hz, 1H), 6.06 (d,
J¼2.3 Hz, 1H), 4.92 (s, 1H), 4.84 (t, J¼1.5 Hz, 1H), 4.57 (t, J¼2.1 Hz),
4.47e4.46 (m, 1H), 3.808 (s, 3H), 3.806 (s, 3H), 3.77 (s, 3H), 3.76 (s,
3H), 3.71 (s, 3H), 3.70. (s, 3H), 3.50 (s, 3H), 2.84 (s, 3H); 13C NMR
5.54 (s, 1H, Hc), 5.47 (s, 1H, Hd), 4.14 (s, 1H, Ha), 3.59 (s, 1H, Hb), 3.54
(s, 3H,]COCH3), 2.97 (s, 3H, ꢀCOCH3).
4.4.8. 2,6a-Dimethoxy-1,4,5-tris(4-methoxyphenyl)-3a-methyl-
1,3a,4,6a-tetrahydropentalene (4j). Compounds 4j were synthe-
sized according to the General Procedure at 0 ꢁC, using propargylic
acetal 1b (70.4 mg, 0.300 mmol) and alkyne 2c (130.4 mg,
0.8920 mmol). Flash chromatography (1:10 EtOAc:pentane) gave
products 4j as yellow oils/waxes.
(150 MHz, CDCl3)
d ppm 159.8, 159.7, 159.6, 159.5, 139.2, 135.0,
134.9, 128.2, 127.9, 125.6, 109.5, 108.1, 95.2, 92.9, 91.5, 90.8, 90.8,
90.5, 60.4, 59.5, 56.2, 56.0, 55.9, 55.7, 55.4, 55.2, 55.1, 54.1, 49.4,14.2;
IR (thin film, cmꢀ1) 2935, 2836, 1692, 1590, 1226, 1204, 1127, 812,
732; HRMS (EI) calcd for C35H40O8 [M]þ 588.2723, obsd 588.2719.
4j-cis-cis-cis (11 mg, 15%, isolated as a mixture with an un-
known isomer): Identification of the isomer was carried out by
comparison with the 4a analogue. The characteristic 1H signals are
given below. Rf¼0.12 (1:10 EtOAc:pentane); 1H NMR (400 MHz,
4.4.11. 1-(3-Methoxy-4-methyl-5-phenylcyclopenta-1,3-dien-1-yl)-
4-nitrobenzene (7). The title compound was synthesized according
to the General Procedure at rt, using propargylic acetal 1d (202 mg,
0.810 mmol) and alkyne 2a (284 mg, 2.43 mmol). Flash chroma-
tography (1:60 EtOAc:pentane) gave compound 7 as an orange
solid/wax (18 mg, 15%): Rf¼0.43 (1:5 EtOAc:pentane); 1H NMR
CDCl3) d
ppm 5.35 (s,1H, Hd), 5.25 (s,1H, Hc), 4.08 (s,1H, Ha), 3.81 (s,
3H), 3.76 (s, 3H), 3.75 (s, 3H), 3.53 (s, 3H,]COCH3), 3.33 (s, 1H, Hb),
3.01 (s, 3H, ꢀCOCH3), 1.02 (s, 3H, CH3).
4j-cis-cis-tr (14.0 mg, 19%): Rf¼0.10 (1:10 EtOAc:pentane); 1H
(400 MHz, CDCl3)
d
ppm 7.97 (d, 2H, J¼9.2 Hz), 7.56 (d, 2H,
NMR (400 MHz, CDCl3)
d
ppm 6.93 (d, 2H, J¼8.2 Hz), 6.87 (d, 2H,
J¼9.1 Hz), 7.27e7.08 (m, 5H), 6.34 (s, 1H), 4.27 (s, 1H), 4.04 (s, 3H),
J¼8.7 Hz), 6.94e6.85 (m, 2H, overlapping), 6.64 (d, 2H, J¼8.6 Hz),
6.59 (d, 2H, J¼8.8 Hz), 6.65e6.42 (m, 2H, overlapping), 6.20 (s, 1H,
Hd), 5.68 (s, 1H, Hc), 4.53 (s, 1H, Ha), 3.71 (s, 3H), 3.70 (s, 3H), 3.67 (s,
3H), 3.57 (s, 3H,¼COCH3), 3.53 (s, 1H, Hb), 3.07 (s, 3H, -COCH3), 1.07
1.86 (d, 3H, J¼1.3 Hz); 13C NMR (100 MHz, CDCl3)
d ppm 162.7,
155.3, 143.3, 141.7, 138.5, 129.0, 127.8, 127.0, 125.2, 123.7, 120.0,
116.5, 58.5, 58.1, 15.5; IR (film, cmꢀ1) 2924, 2841, 1589, 1515, 1331,
1315, 1107, 852, 752, 735, 699; HRMS (EI) calcd for C19H17NO3 [M]þ
308.1287, obsd 308.1287.
(s, 3H, CH3); 13C NMR (100 MHz, CDCl3)
d ppm 158.2, 157.6, 157.4,
156.7, 138.0, 135.9, 132.1, 130.9, 130.5, 130.2, 129.9, 113.0, 112.6,
112.4, 106.2, 86.3, 70.6, 65.8, 55.1, 55.04, 55.00, 54.4, 51.3, 50.9, 16.8;
IR (thin film, cmꢀ1) 2935, 2826, 1609, 1509, 1463, 1245, 1178, 1035,
910, 826, 794, 730; HRMS (EI) calcd for C32H34O5 [M]þ 498.2406,
obsd 498.2398.
4.4.12. 2,5,8a-Trimethoxy-1-(4-methoxyphenyl)-1,3a,8,8a-tetrahy-
drocyclopenta[a]indene (8).3 Propargylic acetal 1b and alkynes 2e, f,
g, h were mixed according to the General Procedure. Full conver-
sion of acetal 1b at 0 ꢁC (1e24 h) afforded dimer 813 (up to 15%) and
propargyl alcohol (up to 10%), while products 4 could not be
detected.
4j-tr-tr-cis (13.2 mg, 18%): Rf¼0.15 (1:10 EtOAc:pentane); 1H
NMR (400 MHz, CDCl3)
d
ppm 6.94 (d, 2H, J¼8.8 Hz), 6.85 (d, 2H,
J¼8.5 Hz), 6.75 (d, 2H, J¼8.8 Hz), 6.62 (d, 2H, J¼8.7 Hz), 7.19e6.61
(m, 4H, overlapping), 5.76 (s, 1H, Hc), 5.16 (s, 1H, Hd), 4.13 (s, 1H, Ha),
3.81 (s, 3H), 3.73 (s, 3H), 3.69 (s, 3H), 3.60 (s, 3H,¼COCH3), 3.36 (s,
1H, Hb), 3.06 (s, 3H, -COCH3), 1.74 (s, 3H, CH3); 13C NMR (100 MHz,
Acknowledgements
We thank the Research Council of Norway for financial support.
CDCl3) d ppm 158.7,158.3,157.8, 157.6,146.5,133.0,130.2,130,129.4,
128.3, 127.1, 113.2, 112.8, 107.1, 89.5, 68.7, 59.1, 55.19, 55.16, 55.0,
54.7, 50.5, 48.7, 13.8; IR (thin film, cmꢀ1) 2930, 2909, 2826, 1610,
1510, 1463, 1246, 1177, 1099, 1036, 824, 732; HRMS (EI) calcd for
Supplementary data
Supplementary data (spectroscopic data 1H and 13C NMR) as-
sociated with this article can be found in the online version, at
http://dx.doi.org/10.1016/j.tet.2015.12.080.
C
32H34O5 [M]þ 498.2406, obsd 498.2402.
4.4.9. 3a-Ethyl-2,6a-dimethoxy-1,5-bis(4-methoxyphenyl)-4-phenyl-
1,3a,4,6a-tetrahydropentalene (4k). The title compound was syn-
thesized according to the General Procedure at 0 ꢁC, using prop-
argylic acetal 1b (151.1 mg, 0.6449 mmol) and alkyne 2i (260.0 mg,
1.997 mmol). Flash chromatography (1:20 EtOAc:pentane) gave
product 4k as a pale yellow oil.
References and notes
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(s, 1H, Hd), 5.29 (s, 1H, Hc), 4.02 (s, 1H, Ha), 3.76 (s, 3H), 3.73 (s, 3H),
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