Gold-catalysed activation of epoxides: Application in the synthesis of bicyclic ketals

Article abstract of DOI:10.1002/ejoc.201001214

Gold-catalysed generation of diol equivalents from epoxides and their intramolecular reaction with Ca≡C bonds to generate bicyclic ketals is presented. This reaction essentially involves the formation of an acetonide, which subsequently cyclises on the alkyne intramolecularly under gold catalysis conditions. This method could be extended to make optically pure bicyclic ketals. Deuterium incorporation experiments were carried out to ascertain the mechanism of the reaction. Sequential activation of epoxide and alkyne moieties by a gold catalyst in acetone as solvent has been achieved. This strategyhas been employed to synthesise bicyclic ketals from epoxy alkynes. Copyright

Full text of DOI:10.1002/ejoc.201001214

FULL PAPER
DOI: 10.1002/ejoc.201001214
Gold-Catalysed Activation of Epoxides: Application in the Synthesis of Bicyclic
Ketals
Rengarajan Balamurugan,*[a] Raveendra Babu Kothapalli,[a] and Ganesh Kumar Thota[a]
Dedicated to the memory of Professor Ramasubbu Jeyaraman
Keywords: Homogeneous catalysis / Gold / Oxygen heterocycles / Cyclization / Epoxides / Alkynes / Bicyclic ketals
Gold-catalysed generation of diol equivalents from epoxides
cyclises on the alkyne intramolecularly under gold catalysis
and their intramolecular reaction with CϵC bonds to gener- conditions. This method could be extended to make optically
ate bicyclic ketals is presented. This reaction essentially in-
volves the formation of an acetonide, which subsequently
pure bicyclic ketals. Deuterium incorporation experiments
were carried out to ascertain the mechanism of the reaction.
of α- and β-alkynyl epoxides with the aid of gold catalysts
have been reported.[9] In these reactions, because of the alk-
ynophilicity of gold catalysts, intramolecular nucleophilic
attack of the oxirane oxygen on the gold-activated alkyne
via an oxonium ion intermediate has been proposed. Simi-
larly, the use of allene-epoxide cascade reactions to generate
polycyclic skeletons has been reported.[3p] Pale et al., ex-
ploiting the dual coordination behaviour of gold catalysts,
have demonstrated rearrangements of alkynyloxiranes into
divinyl ketones.[10] With the aid of DFT calculations it was
later shown that the multifaceted coordination behaviour of
the gold catalyst is responsible for a sequential coordination
to the triple bond and then to the lone pair of oxygen to
bring about the conversion.[11] On the other hand, acti-
vation of epoxide followed by alkyne activation has been
put forward to explain the formation of substituted furans
from α-alkynyl epoxides in the presence of external nucleo-
philes.[12] Recently, Shi et al. evoked both possible initial ac-
tivations (alkyne or oxirane) by gold catalyst in the cyclo-
isomerisation of δ-alkynyl epoxides into cyclic ketals in the
presence of water/alcohol nucleophiles.[13a] In their later re-
port, they strongly favoured the involvement of oxonium
ion intermediates in these reactions.[13b] In this context, we
wished to develop a reaction system with which one could
unambiguously activate the oxirane ring first with the aid
of a gold catalyst and then further achieve cycloisomeri-
sation on a suitably placed triple bond.
Introduction
The chemical synthesis of the complex structural motifs
present in natural products by simple strategies is a chal-
lenging task. In this regard, cascade reactions occupy a
leading position in accomplishing the production of such
structural motifs in simpler ways.[1] In such transforma-
tions, transition-metal-catalysed cascade reactions in par-
ticular have a wide scope in terms of selectivity and effi-
ciency.[2] More recently, gold compounds, being soft car-
bophilic Lewis acids, have been developed to provide versa-
tile catalysts for such strategies. Many gold-catalysed cas-
cade reactions have been developed in recent years.[3] In
most of them the carbophilicity of gold catalysts has been
exploited.[4] Yamamoto has recently shown, from computed
values of heats of formation, that both gold(I) and gold(III)
possess considerable oxophilicity.[5] As is evident from the
limited literature, this property of gold catalysts has not
been utilised very much. Most of these reports involve the
activation of a carbonyl function.[6] We considered the de-
velopment of systems in which oxophilicity and carbophil-
icity of gold catalysts could be used in tandem to develop
new reactions. In this context we have recently developed
gold-catalysed reactions between phenylacetaldehydes/
phenylmethyl ketones and arylalkynes to make substituted
naphthalenes, as well as transglycosylation on per-O-ace-
tylglycals.[7]
Epoxides are attractive building blocks for the construc-
tion of interesting molecular skeletons.[8] Transformations
Results and Discussion
[a] School of Chemistry, University of Hyderabad,
Gachibowli, Hyderabad 500046, India
In order to achieve the objective, the ring-opening of ep-
oxides was studied first. It is known that the Au–O bond is
weak.[14] We wished to utilise this character in the ring-
opening of epoxides because the oxyanion of the ring-
Fax: +91-40-2301-2460
E-mail: rbsc@uohyd.ernet.in
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001214.
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R. Balamurugan, R. B. Kothapalli, G. K. Thota
FULL PAPER
opened system will be more nucleophilic. With a weak nu- to scrambling of stereochemistry, because the acetone can
cleophile such as acetone, which can assist the gold-cata- approach from either side of the carbocation. Under the
lyst-activated ring-opening of an epoxide, the formation of reaction conditions, only stilbene oxide showed some
acetonide is expected. It was planned, once the acetonide carbocationic rearrangement, to result in a 14% yield of
had been formed under gold catalysis conditions, to per- diphenylacetaldehyde along with the expected mixture of
form intramolecular cyclisation on a suitably placed triple cis and trans acetonides. Interestingly, with the substrate 1n,
bond.
the formation of 2,3-dihydro-2-(hydroxymethyl)benzofuran
In this context, different epoxides were treated with in significant amounts along with the expected product 2n
AuCl3 in acetone (2 mol-%). Corresponding acetonide de- was observed. This product might have been formed
rivatives were obtained in good to excellent yields (Table 1). through initial gold-catalysed debenzylation of the aryl
Different Lewis acids[15] and other systems[16] have been re- benzyl ether followed by the attack of the phenolic hydroxy
ported to effect this transformation. More than half of the group on the epoxide ring. This result is not surprising, be-
reported methods require higher reaction temperatures. The cause certain Lewis acids are already known to debenzylate
advantage of AuCl3 is that strictly anhydrous conditions, aryl benzyl ethers and benzyl-protected sugars.[17]
such as are required for many sensitive Lewis acids, are not
With a tethered alkynic moiety as in the substrate 3, for-
necessary; the reactions could be carried out with distilled mation of the bicyclic ketal 4 in small amounts was noted
acetone itself. The reactions were exceptionally smooth and after the system had been heated at reflux for 11 h (Table 2).
went quickly to completion at room temperature.
Bicyclic ketal scaffolds are found in many natural products
with a range of bioactivities.[18] Different synthetic strate-
gies have been developed in order to access bicyclic ketal
natural products/motifs.[13,18–20] Metal catalysts such as
platinum and gold salts have been used in intramolecular
oxycyclisations of alkynediols to produce bicyclic ket-
als.[13,20] The formation of the bicyclic ketal under our reac-
tion conditions prompted us to probe this reaction further
to make it synthetically useful. In this respect, improvement
in the yield of the bicyclic ketal was noted when AgSbF6
was added to AuCl3, but the result was not impressive from
the synthetic perspective. Although there was no reaction
with Ph3PAuCl, cationic gold(I) generated from a combina-
tion of Ph3PAuCl and AgSbF6 worked well for the forma-
tion of bicyclic ketals and afforded 4 and 5 in good yields
(Entry 4). While we were preparing this manuscript, Al-
caide and co-workers published gold/acid-co-catalysed
preparations of bicyclic ketals from alkynic acetonides.[20e]
It is important to note that with AgSbF6 alone the epoxy
alkyne gave only its corresponding 1,3-dioxolane derivatives
(Entry 5). It has been found that some of the reported gold-
catalysed reactions are actually due to Brønsted acid cataly-
sis, which might operate under certain reaction condi-
tions.[21] Alcohol addition to C=C bonds, which has been
Table 1. AuCl3-catalysed formation of acetonide derivatives from
epoxides.
R1
R2
R3
Time 2, yield[a,b]
[min]
1a Ph
H
H
H
H
H
H
H
H
H
H
15
5
2a, 73%
2b, 87%
2c, 78%
2d, 83%
1b p-ClC6H4
1c PhOCH2
1d BnOCH2
1e Ph(CH2)3OCH2
1f Ph
1g Ph
1h Ph
1i Ph
1j BnOCH2
1k BnOCH2
1l (PhO2S)2CHCH2
1m PhCH2CH(OBn)CH2
1n (o-BnOC6H4)CH2
40
25
90
15
20
20
25
85
2e, 84%
CH2OBn H
CH2OAc H
CO2Et
Ph
2f, 82% (1:1)
2g, 74% (2.5:1)
2h, 92% (1.8:1)
2i, 77% (1:4.9)[c]
2j, 92% (0:1)
2k, 88% (1:0)
2l, 52%
H
H
BnOCH2 H
H
H
H
H
BnOCH2 90
H
H
H
75
10
15
[d]
2m, 81% (1:1)
2n, 52%[e]
[a] Isolated yield. [b] Values in the parentheses refer to the cis/trans
ratio based on integrations in the 1H NMR spectrum. [c] Diphenyl-
acetaldehyde was also formed, in 14% yield. [d] Diastereomeric
mixture (1:1). [e] 2,3-Dihydro-2-(hydroxymethyl)benzofuran was
also formed, in 43% yield.
Table 2. Optimisation of reaction condition for the bicyclic ketal
formation.
Both monosubstituted and vicinally disubstituted epox-
ides were studied. Disubstituted epoxides with aryl groups
as the substituents gave mixtures of the cis and trans dioxol-
ane derivatives 2f–2i, whereas dialkyl-substituted epoxides
1j and 1k gave the corresponding dioxolane derivatives 2j
and 2k in a completely stereospecific manner. The cis epox-
ides gave trans dioxolane derivatives and vice versa because
of the SN2 attack of the acetone solvent on the gold-acti-
vated epoxide ring. Nucleophilic assistance of this kind is
required to open the epoxide ring.[15b] In an aryl-substituted
epoxide, the generated carbocation is stabilised by the aryl
Entry Catalyst
Time [h] Yield 4/5/6[a,b]
1
2
3
4
5
6
AuCl3 (2 mol-%)
AuCl3/3AgSbF6 (2 mol-%)
Ph3PAuCl (2 mol-%)
Ph3PAuCl/AgSbF6 (2 mol-%) 6 h
AgSbF6 (2 mol-%)
TfOH (5 mol-%)
11 h
12 h
11 h
6:0:85 (1:1.4)
20:7:30 (1:13)
0:0:0
46:30:3 (0:1)
0:0:82 (1.2:1)
0:0:56 (1:1.9)
8 h
5 h
[a] Isolated yields. [b] Values in parentheses correspond to the
group (see the mechanism given in Scheme 5). This leads cis/trans ratios in compounds 6.
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Gold-Catalysed Activation of Epoxides
carried out under gold catalysis conditions, for example, ever, because epoxy alkyne substrate containing ether link-
could be carried out with the Brønsted acid TfOH as cata- age similar to those in our study cleaved under their reac-
lyst.[22] Similarly, hydration and alcohol addition to unsym- tion conditions. This is probably due to the potential for
metrical aryl-substituted alkynes in the presence of catalytic water to attack directly on the gold-activated alkyne. Our
PTSA has been reported by Brion and co-workers.[23] We method, though, utilises mild nucleophilic acetone to open
therefore felt it would be wise to check whether Brønsted the epoxide ring for subsequent bicyclic acetal formation.
acid catalysis was playing any role in the present reaction. Unlike water, acetone does not attack the gold-activated
Heating of 3 with TfOH in acetone at reflux resulted only alkyne.
in a mixture of cis and trans acetonides along with some
A series of epoxy alkyne derivatives with different substi-
decomposed materials (Entry 6), so it can be assumed that tution patterns were synthesised and subjected to cascade
the formation of the bicyclic ketal is not through Brønsted cyclisation conditions (Ph3PAuCl/AgSbF6 in acetone under
acid catalysis.
reflux). The results are presented in Table 3. TLC analysis
This strategy is distinct from the previously reported re- of the reaction mixtures revealed the formation of acetonide
lated metal-mediated bicyclic ketal synthesis involving an derivatives first and their subsequent transformation into
intramolecular nucleophilic attack at an alkyne.[13,20c,20e] In the corresponding bicyclic ketal derivatives. To confirm the
the reactions between butane 1,2-diacetal (BDA) protected above observation, the cis- and trans-1,3-dioxolane deriva-
[20c]
alkynediols and PtCl4
or alkynic acetonides and tives 6a and 6b, respectively, were prepared from the epoxy
Ph3PAuCl/AgOTf, PTSA[20e] the starting material has the alkyne 3 and heated at reflux separately in acetone with
diol component already in it. On the other hand, water has Ph3PAuCl/AgSbF6.[24] It was found that the cis-dioxolane
been used as nucleophile in gold-catalysed cyclisations of 6a gave the endo bicyclic ketal 4 and its trans counterpart
epoxy alkynes.[13] Only a limited scope was reported, how- 6b gave the exo product 5. These observations clearly rule
Table 3. Ph3PAuCl/AgSbF6-catalysed formation of bicyclic ketal derivatives from epoxy alkynes.[a]
[a] All the reactions were carried out in acetone under reflux. [b] Isolated yields. [c] Catalyst (2 mol-%). [d] Catalyst (3 mol-%). [e] Catalyst
(4 mol-%).
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FULL PAPER
out the possibility of simultaneous intramolecular attack of and 20 revealed the endo orientations of the p-nitrophenyl
the oxirane oxygen at the gold-activated alkyne and oxirane and benzyl substituents, respectively.[25] Even a [4.2.1]bicy-
ring-opening by acetone. When the epoxide ring had an aryl clic ketal could be made by this strategy (Entry 14).
substituent a mixture of endo and exo products was ob-
To evaluate the scope further, the enantiomerically pure
tained. These could easily be separated by column epoxy alkyne derivatives 40 and 43 (Scheme 1) were pre-
chromatography. The epoxy alkyne derivative 17, bearing pared by Sharpless asymmetric epoxidation.[26] Cascade
two alkyl substituents on the oxirane ring in cis fashion, cyclisation of 40 under the reaction conditions resulted in
gave the exo product 18 exclusively, through SN2 attack of the formation of two separable isomers of the correspond-
acetone on the oxirane ring during the acetonide formation. ing bicyclic acetals 41 and 42, with preservation of the en-
On the other hand, substrates containing aryl groups or antiomeric excess in the starting epoxy alkyne 40. Similarly,
trialkyl substituents on the epoxide gave mixtures of exo the reaction of 43 resulted in the formation of the corre-
and endo products. This is because the aryl/dialkyl substitu- sponding separable opposite diastereomers 44 and 45 with
ent on the oxirane ring will stabilise the carbocation gener- preservation of the enantiomeric excess in the starting ep-
ated upon ring-opening of epoxides, and this is eventually oxy alkyne 43. These results clearly show that the epoxide
attacked by acetone from either side.[15b] A trimethylsilyl opening occurred at the benzylic carbon. This methodology
group on the alkyne did not survive under the reaction con- could thus be used to access all possible diastereomers of
ditions, with the corresponding desilylated products being the bicyclic ketal derivative.
obtained. Treatment of 7 with Ph3PAuCl/AgSbF6 in [D6]-
In order to establish the mechanism of the cyclisation,
acetone revealed that the desilylation occurred before the two different experiments were performed. Firstly, the gold-
formation of the bicyclic ketal. Analysis of the reaction catalysed cyclisation of the epoxy alkyne derivative 14
mixture after 1 h showed considerable deuterium incorpo- (Scheme 2) was carried out in deuterated acetone.[27] This
ration in the place of SiMe3 in the intermediate acetonides. reaction resulted in deuterium incorporation (Ն90%) at the
Furthermore, the bicyclic ketals formed in the reaction time methylene carbon α to the ester function in the products 46
(1 h) did not contain the SiMe3 group. The stereochem- and 47. Furthermore, the acetonide derivative 49a
istries of the substituents in the bicyclic ketal products were (Scheme 2), derived from 14, also gave the product 46, with
assigned by X-ray crystal structure analysis and comparison slightly less deuterium incorporation (85%), under the same
of spectroscopic data with those for similar compounds re- reaction conditions. The reactions in [D6]acetone were slow,
ported in the literature.[20c] X-ray structure analyses of 12 hinting at a possible isotope effect. These results emphasise
Scheme 1. Synthesis of enantiomerically pure bicyclic ketals.
Scheme 2. Deuterium incorporation studies.
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Gold-Catalysed Activation of Epoxides
Scheme 3. Control experiments for deuterium incorporation studies.
the involvement of acetone in the protodemetallation dur- studied. For this purpose the reaction behaviour of the sub-
ing the cyclisation.
strate 52a (Scheme 4) was studied. The reaction of 52a gave
As control experiments, the undeuterated bicyclic ketals the bicyclic ketal 4 and 1,3-diphenylpropan-2-one (53), in
15 and 16 (Scheme 3) were treated separately with 48% and 65% yields, respectively. Compound 52a had been
Ph3PAuCl/AgSbF6 (2 mol-%) in [D6]acetone at reflux. prepared from the corresponding diol 54[29] and 1,3-di-
Whereas the substrate 15 showed 35% α-deuterium incor- phenylpropan-2-one.[30] So attack of water at the dioxolane
poration, substrate 16 did not behave in this way.[28] One ring is a realistic way to explain the formation of 53 from
possible explanation might be that the ketal in the bicyclic 52a. The presence of adventitious water in the acetone sol-
substrate 15 can open up and set up an equilibrium with the vent to play the role could be excluded because deuterium
diol keto ester. The ring-opened species could incorporate incorporation was observed in the reactions that were car-
deuterium at the active methylene site. In another experi- ried out in [D6]acetone. Moreover, this shows that the water
ment, compound 3 was treated with catalytic Ph3PAuCl/ had to come from acetone. Under the Lewis-acidic condi-
AgSbF6 in [D6]acetone under reflux. High levels of deute- tions there is a great likelihood that the acetone solvent will
rium incorporation at the methyl substituents in the bicyclic undergo aldol self-condensation to generate water. The
ketals were observed. Interestingly, in the endo isomer, a slowness of the reactions in [D6]acetone could have arisen
considerable amount of deuterium incorporation at the ring from the isotopic effects involved in the above reaction.
methylene was observed. This deuterium incorporation, as Furthermore, when 14 (Scheme 4) was treated with
had also occurred with the endo bicyclic ketal 15, might AuCl(PPh3)/AgSbF6 in acetone in the presence of molecu-
have taken place when the bicyclic ketal opened under the lar sieves (4 Å) the reaction stopped at the acetonide forma-
reaction condition.
tion stage. These experiments clearly indicate that water
The involvement of acetone during protodemetallation that is slowly formed from acetone plays a vital role in the
being clear, the fate of the initially formed acetonide was cyclisation.
Scheme 4. Experimental support for the formation of water under the reaction conditions.
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R. Balamurugan, R. B. Kothapalli, G. K. Thota
FULL PAPER
Scheme 5. Tendative mechanism for the formation of bicyclic acetal.
Scheme 6.
A mechanism based on the above observations is pro- tion will give IX. Another intramolecular oxy-cyclisation on
posed as shown in Scheme 5. Initially the oxirane ring of the gold-activated double bond, followed by acetone elimi-
the epoxy alkyne I is opened by the Lewis acid with the nation would generate XI, which on protodemetallation
nucleophilic assistance of the acetone solvent. The ring- would furnish the exo bicyclic ketal XII. On the other hand
opened species III and IV give a mixture of cis and trans (pathway 2), the acetonide V could enter into an equilib-
acetonides V. To give the bicyclic ketal, the intermediate V rium with the diol XIII with the assistance of Lewis acid
can, in principle, take either pathway 1 or pathway 2. To and water generated from the acetone solvent.[32] Now the
demonstrate the stereospecificity involved in the bicyclic ket- diol could cyclise intramolecularly on the triple bond under
al formation from the acetonide, the trans isomer of the gold catalysis.[33] This pathway is more viable than path-
acetonide V is shown in the cyclisation pathways 1 and 2. way 1, because after 15 min in the presence of AuCl(PPh3)/
It is known that oxygen in an acetonide can act as nucleo- AgSbF6 in acetone the diol 54 had given rise to small
phile.[31] The acetonide oxygen can hence attack the gold- amounts of the bicyclic acetals 4 and 5, although the major
activated triple bond to give the intermediate VII as shown products were the acetonides 6a and 6b (Scheme 6). In a
in pathway 1. Water generated under the reaction condi- similar manner the cis isomer of V would give the endo
tions can attack at this stage and subsequent protodemetalla- bicyclic ketal.
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Gold-Catalysed Activation of Epoxides
10.0, 5.6 Hz, 1 H, -CHHbOBn), 1.42 (s, 3 H, -CH3), 1.37 (s, 3 H,
-CH3) ppm.
Conclusions
In summary, we have shown that epoxides can be con-
verted into acetonides, which can serve as diol equivalents
for further transformation under gold catalysis conditions
in acetone. This has been successfully applied to the synthe-
sis of bicyclic ketals and could also be extended to make
Compound 2e: Colourless liquid; Rf = 0.50 in EtOAc/hexanes (1:5,
double elution). 1H NMR (400 MHz, CDCl3): δ = 7.29–7.26 (m, 2
H, Ph-H), 7.19–7.17 (m, 3 H, Ph-H), 4.30–4.24 (m, 1 H, 4-H), 4.06
(dd, J = 7.6, 6.8 Hz, 1 H, 5-Ha), 3.74 (dd, J = 7.6, 7.2 Hz, 1 H, 5-
Hb), 3.53–3.40 (m, 4 H, -CH2OCH2), 2.68 (t, J = 7.6 Hz, 2 H,
optically pure isomers. It has been found that the water -CH2Ph), 1.94–1.87 (m, 2 H, -CH2CH2Ph), 1.43 (s, 3 H, -CH3),
1.37 (s, 3 H, CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 141.8,
128.4, 128.3, 125.7, 109.3, 74.7, 71.8, 70.7, 66.8, 32.2, 31.0, 26.7,
formed from the acetone solvent under the reaction condi-
tion plays a crucial role in the cyclisation of the acetonide
on the triple bond. Other synthetic utilisation of this strat-
egy is currently under investigation.
25.4 ppm. IR (neat): ν = 2934, 2865, 1603, 1454, 1371, 1118, 847
˜
cm–1. C15H22O3 (250.34): calcd. C 71.97, H 8.86; found C 71.85, H
8.91.
1
Compound 2f:[15o] cis/trans 1:1. H NMR (400 MHz, CDCl3): δ =
7.32–7.14 (m, 20 H, Ph-H), 5.27 (d, J = 7.1 Hz, 1 H, 4-H), 4.85 (d,
J = 8.6 Hz, 1 H, 4-H), 4.65–4.54 (m, 3 H, OCH2Ph, 5-H), 4.30 (d,
J = 11.8 Hz, 1 H, OCHaHPh), 4.16 (d, J = 11.9 Hz, 1 H,
OCHHbPh), 4.02–3.99 (m, 1 H, 5-H), 3.68 (dd, J = 10.8, 3.0 Hz,
1 H, CHaHOBn), 3.63 (dd, J = 10.7, 5.2 Hz, 1 H, CHHbOBn),
3.20 (dd, J = 10.0, 7.2 Hz, 1 H, -CHaHOBn), 3.00 (dd, J = 10.0,
4.8 Hz, 1 H, -CHHbOBn), 1.65 (s, 3 H, -CH3), 1.58 (s, 3 H, -CH3),
1.54 (s, 3 H, -CH3), 1.49 (s, 3 H, -CH3) ppm.
Experimental Section
General Methods: 1H and 13C spectra were recorded with a
400 MHz NMR spectrometer and solutions in CDCl3 with tet-
ramethylsilane (TMS) as internal standard. IR spectra were re-
corded with an FT/IR spectrometer. Elemental (C, H, N) analysis
were performed by the flash combustion method with a CHN ana-
lyser. The X-ray diffraction measurements were carried out at
100 K and 298 K with an automated diffractometer and graphite
monochromated Mo-Kα (λ = 0.71073 Å) radiation with CAD4
software or the X-ray intensity data were measured at 100 K and
298 K with a CCD area detector system fitted with a graphite mon-
ochromator and a Mo-Kα fine-focus sealed tube (λ = 0.71073 Å).
Column chromatography was performed on silica gel (100–
200 mesh), with ethyl acetate/hexanes mixtures as eluents. HPLC
analysis of the samples was performed with a Daicel Chiralcel OD-
H column and hexanes/iPrOH as eluent (flow rate = 0.5 mLmin–1
at λmax = 220 nm). Most of the starting materials were prepared by
known and standard literature procedures. Acetone was dried with
KMnO4 and stored over molecular sieves (4 Å). THF was dried
with sodium and freshly distilled before use.
Compound 2g:[15o] cis/trans 2.5:1; trans isomer: 1H NMR
(400 MHz, CDCl3): δ = 7.39–7.32 (m, 5 H, Ph-H), 4.77 (d, J =
8.8 Hz, 1 H, 4-H), 4.35 (dd, J = 11.6, 3.2 Hz, 1 H, -CHaHOAc),
4.14 (dd, J = 12.0, 6.0 Hz, 1 H, -CHHbOAc), 4.04–4.00 (m, 1 H,
5-H), 2.06 (s, 3 H, OCOCH3), 1.59 (s, 3 H, -CH3), 1.53 (s, 3 H,
-CH3) ppm. cis Isomer: 1H NMR (400 MHz, CDCl3): δ = 7.39–
7.29 (m, 5 H, Ph-H), 5.32 (d, J = 7.2 Hz, 1 H, 4-H), 4.59–4.55 (m,
1 H, 5-H), 3.71 (dd, J = 11.6, 4.4 Hz, 1 H, CHaHOAc), 3.62 (d, J
= 11.6, 8.0 Hz, 1 H, CHHbOAc), 1.91 (s, 3 H, OCOCH3), 1.65 (s,
3 H, -CH3), 1.49 (s, 3 H, -CH3) ppm.
Compound 2h:[15n] cis/trans 1.8:1. 1H NMR (400 MHz, CDCl3): δ
= 7.44–7.29 (m, 10 H, Ph-H), 5.44 (d, J = 7.6 Hz, 1 H, 5-H), 5.16
(d, J = 7.6 Hz, 1 H, 5-H), 4.83 (d, J = 7.2 Hz, 1 H, 4-H), 4.34 (d,
J = 7.6 Hz, 1 H, 4-H), 4.29–4.21 (m, 2 H, -CH2CH3), 3.76–3.72
(m, 1 H, -CHaHCH3), 3.58–3.54 (m, 1 H, -CHHbCH3), 1.80 (s, 3
H, -CH3), 1.62 (s, 3 H, -CH3), 1.59 (s, 3 H, -CH3), 1.51 (s, 3 H,
-CH3), 1.28 (t, J = 7.2 Hz, 3 H, -CH2CH3), 0.78 (t, J = 7.2 Hz, 3
H, -CH2CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.3, 169.4,
137.7, 135.7, 128.6, 128.5, 128.4, 128.1, 126.8, 126.5, 111.6, 111.1,
81.4, 80.8, 79.9, 79.0, 61.4, 60.6, 26.9, 26.6, 25.8, 25.3, 14.1,
13.5 ppm.
General Procedure for the AuCl3-Catalysed Acetonide Formation:
AuCl3 (0.01 mmol) was added to a solution of an epoxide
(0.5 mmol) in acetone (5 mL). The reaction mixture was stirred at
room temperature. After stirring for the specified time given in
Table 1, solvent was removed in a rotary evaporator. The residue
was loaded on a silica gel column. It was eluted with an ethyl acet-
ate/hexanes mixture to get the pure acetonide.
Compound 2a:[15j] 1H NMR (200 MHz, CDCl3): δ = 7.39–7.32 (m,
5 H, Ph-H), 5.08 (dd, J = 7.8, 5.8 Hz, 1 H, 4-H), 4.32 (dd, J = 7.8,
5.8 Hz, 1 H, 5-Ha), 3.72 (t, J = 7.8 Hz, 1 H, 5-Hb), 1.56 (s, 3 H,
-CH3), 1.50 (s, 3 H, -CH3) ppm.
Compound 2i:[15o] cis/trans 1:4.9; trans isomer: 1H NMR (400 MHz,
CDCl3): δ = 7.34–7.22 (m, 10 H, Ph-H), 4.75 (s, 2 H, 4-H, 5-H),
1.68 (s, 6 H, -CH3) ppm. cis Isomer: 1H NMR (400 MHz, CDCl3):
δ = 7.35–7.20 (m, 10 H, Ph-H), 5.5 (s, 2 H, 4-H, 5-H), 1.83 (s, 3
H, -CH3), 1.62 (s, 3 H, -CH3) ppm.
Compound 2b:[15o] 1H NMR (200 MHz, CDCl3): δ = 7.34–7.28 (m,
4 H, Ar-H), 5.04 (t, J = 6.8 Hz, 1 H, 4-H), 4.30 (dd, J = 8.0, 6.0 Hz,
1 H, 5-Ha), 3.66 (t, J = 8.0 Hz, 1 H, 5-Hb), 1.54 (s, 3 H, -CH3),
1.48 (s, 3 H, -CH3) ppm.
Compound 2j:[34] 1H NMR (400 MHz, CDCl3): δ = 7.32–7.20 (m,
10 H, Ph-H), 4.53 (brs, 4 H, OCH2Ph), 4.0 (brs, 2 H, 4-H, 5-H),
3.56 (brs, 4 H, -CH2OBn), 1.38 (brs, 6 H, -CH3) ppm. 13C NMR
(100 MHz, CDCl3): δ = 138.0, 128.4, 127.8, 127.7, 109.7, 77.6, 73.6,
70.7, 27.1 ppm.
Compound 2c:[15o] 1H NMR (400 MHz, CDCl3): δ = 7.32–7.28 (m,
2 H, Ph-H), 6.99–6.92 (m, 3 H, Ph-H), 4.49 (pent, J = 6.0 Hz, 1
H, 4-H), 4.18 (dd, J = 8.4, 6.4 Hz, 1 H, 5-Ha), 4.08 (dd, J = 9.2,
5.2 Hz, 1 H, 5-Hb), 3.97–3.90 (m, 2 H, -CH2OPh), 1.48 (s, 3 H,
-CH3), 1.42 (s, 3 H, -CH3) ppm.
Compound 2k: Colourless liquid; Rf = 0.63 in EtOAc/hexanes 1:1.
1H NMR (400 MHz, CDCl3): δ = 7.36–7.28 (m, 10 H, Ph-H), 4.57
Compound 2d:[15j] 1H NMR (400 MHz, CDCl3): δ = 7.35–7.27 (m, (d, J = 12.0 Hz, 2 H, OCH2Ph), 4.48 (d, J = 12.0 Hz, 2 H,
5 H, Ph-H), 4.60 (d, J = 12.0 Hz, 1 H, OCHaHPh), 4.56 (d, J = OCH2Ph), 4.36 (t, J = 4.0 Hz, 2 H, 4-H, 5-H), 3.60 (dd, J = 9.6,
12.4 Hz, 1 H, -OCHHbPh), 4.31 (pent, J = 6.4 Hz, 1 H, 4-H), 4.06
(dd, J = 8.0, 6.4 Hz, 1 H, 5-Ha), 3.74 (dd, J = 8.0, 6.4 Hz, 1 H, 5- 1.46 (s, 3 H, -CH3), 1.38 (s, 3 H, -CH3) ppm. 13C NMR (100 MHz,
Hb), 3.56 (dd, J = 10.0, 6.0 Hz, 1 H, -CHaHOBn), 3.48 (dd, J = CDCl3): δ = 137.9, 128.4, 127.8, 127.7, 108.9, 75.9, 73.5, 68.7, 27.9,
4.8 Hz, 2 H, -CH2OBn), 3.50 (dd, J = 10.0, 6.0 Hz, 2 H, -CH2OBn),
Eur. J. Org. Chem. 2011, 1557–1569
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1563

R. Balamurugan, R. B. Kothapalli, G. K. Thota
FULL PAPER
25.4 ppm. C21H26O4 (342.43): calcd. C 73.66, H 7.65; found C
73.45, H 7.61.
H, 4-H), 1.55 (s, 3 H, -CH3) ppm. 13C NMR (100 MHz, CDCl3):
δ = 141.9, 128.5, 127.8, 126.0, 106.3, 81.5, 80.4, 72.2, 68.3,
19.6 ppm. IR (neat): ν = 2965, 2916, 2855, 1605, 1495, 1452, 1393,
˜
Compound 2l: Yellow solid, m.p. 139–141 °C; Rf = 0.42 in EtOAc/
hexanes 1:1. 1H NMR (400 MHz, CDCl3): δ = 8.00 (d, J = 8.0 Hz,
2 H, Ph-H), 7.91 (d, J = 8.0 Hz, 2 H, Ph-H), 7.40–7.54 (m, 6 H,
Ph-H), 4.85 [dd, J = 6.4, 4.8 Hz, 1 H, -CH(SO2Ph)2], 4.54 (pent, J
1238, 1074, 980, 754 cm–1. C12H14O3 (206.24): calcd. C 69.88, H
6.84; found C 69.95, H 6.81.
Compounds 6a and 6b: AuCl3 (13 mg, 2 mol-%) was added under
= 6.0 Hz, 1 H, 4-H), 4.08 (dd, J = 8.8, 6.4 Hz, 1 H, 5-Ha), 3.62 N2 to a solution of the epoxy alkyne 3 (400 mg, 2.13 mmol) in
(dd, J = 8.8, 4.4 Hz, 1 H, 5-Hb), 2.36 [t, J = 5.6 Hz, 2 H, acetone (10 mL). The reaction mixture was allowed to stir at room
-CH2CH(SO2Ph)2], 1.28 (s, 3 H, -CH3), 1.18 (s, 3 H, -CH3) ppm. temperature for 15 min. Solvent was removed from the reaction
13C NMR (100 MHz, CDCl3): δ = 138.5, 137.4, 134.5, 129.6, 129.4, mixture and the crude product was purified by column chromatog-
129.1, 109.7, 79.9, 72.6, 68.9, 31.1, 26.8, 25.2 ppm. IR (neat): ν =
raphy with EtOAc/hexanes (1:12) as eluent to separate 6a (241 mg,
˜
2988, 2920, 1732, 1585, 1379, 1147, 829 cm–1. C19H22O6S2 (410.50): 46%) and 6b (225 mg, 43%).
calcd. C 55.59, H 5.40; found C 55.68, H 5.36.
Compound 6a: Colourless liquid; Rf = 0.41 in EtOAc/hexanes (1:10,
Compound 2m: cis/trans 1:1; colourless liquid; Rf = 0.58 in EtOAc/
hexanes (1:5, double elution). 1H NMR (400 MHz, CDCl3): δ =
double elution). 1H NMR (400 MHz, CDCl3): δ = 7.36–7.27 (m, 5
H, Ph-H), 5.26 (d, J = 7.2 Hz, 1 H, PhCH), 4.57 (dt, J = 10.8,
7.35–7.21 (m, 20 H, Ph-H), 4.54–4.41 (m, 4 H, OCH2Ph), 4.27– 4.4 Hz, 1 H, -OCH2CH), 3.92 (dd, J = 15.6, 2.4 Hz, 1 H, CCH2-
4.19 (m, 2 H, 4-H), 4.02 (dd, J = 8.0, 5.6 Hz, 1 H, 5-Ha), 3.91 (dd, O-), 3.86 (dd, J = 16.0, 2.4 Hz, 1 H, CCH2O-), 3.16 (dd, J = 10.0,
J = 8.0, 6.0 Hz, 1 H, 5-Ha), 3.88–3.81 (m, 1 H, 5-Hb), 3.69 (pent, 8.0 Hz, 1 H, -CHCH2O-), 3.00 (dd, J = 10.4, 4.4 Hz, 1 H,
J = 6.0 Hz, 1 H, 5-Hb), 3.49 [t, J = 8.0 Hz, 1 H, -CH(OBn)CH2Ph],
3.42 [t, J = 8.0 Hz, 1 H, -CH(OBn)CH2Ph], 2.99–2.92 (m, 2 H,
-CH2Ph), 2.86 (dd, J = 14.0, 6.0 Hz, 1 H, -CHaHPh), 2.80 (dd, J
= 13.6, 6.4 Hz, 1 H, -CHHbPh), 1.97 [dt, J = 14.0, 6.4 Hz, 1 H,
-CHaHCH(OBn)CH2Ph], 1.78 [ddd, J = 14.0, 8.0, 2.8 Hz, 1 H,
-CHCH2O-), 2.32 (t, J = 2.4 Hz, 1 H, CCH), 1.66 (s, 3 H, -CH3),
1.47 (s, 3 H, -CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 137.0,
128.2, 128.0, 126.7, 109.0, 79.3, 78.6, 77.4, 74.5, 70.0, 58.3, 27.2,
24.7 ppm. IR (neat): ν = 3287, 2861, 2118, 1721, 1462, 1101,
˜
879 cm–1. C15H18O3 (246.31): calcd. C 73.15, H 7.37; found C
73.17, H 7.42.
-CHHbCH(OBn)CH2Ph], 1.72–1.61 [m,
2 H, CH2CH(OBn)-
CH2Ph], 1.38 (s, 3 H, -CH3), 1.34 (s, 3 H, -CH3), 1.33 (s, 3 H,
-CH3), 1.32 (s, 3 H, -CH3) ppm. 13C NMR (100 MHz, CDCl3): δ
= 138.6, 138.4, 129.7, 128.4, 128.0, 127.9, 127.7, 126.3, 108.6, 108.4,
77.8, 73.6, 73.1, 72.1, 71.3, 70.1, 69.6, 41.2, 40.6, 38.9, 37.5, 27.0,
Compound 6b: Colourless liquid; Rf = 0.54 in EtOAc/hexanes (1:10,
double elution). 1H NMR (400 MHz, CDCl3): δ = 7.42–7.30 (m, 5
H, Ph-H), 4.83 (d, J = 8.8 Hz, 1 H, PhCH), 4.26 (dd, J = 16.0,
2.4 Hz, 1 H, CCH2O-), 4.20 (dd, J = 16.0, 2.4 Hz, 1 H, CCH2O-),
3.99 (ddd, J = 8.4, 5.2, 2.8 Hz, 1 H, -CH2CH), 3.74 (dd, J = 10.4,
2.8 Hz, 1 H, -CHCH2O-), 3.69 (dd, J = 10.4, 5.2 Hz, 1 H,
-CHCH2O-), 2.43 (t, J = 2.4 Hz, 1 H, CCH), 1.58 (s, 3 H, -CH3),
1.54 (s, 3 H, -CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 137.8,
25.9 ppm. IR (neat): ν = 2932, 2870, 1602, 1454, 1369, 1157,
˜
870 cm–1. C21H26O3 (326.43): calcd. C 77.27, H 8.03; found C
77.35, H 8.12.
Compound 2n:[15o] 1H NMR (400 MHz, CDCl3): δ = 7.44–7.32 (m,
5 H, Ph-H), 7.23–7.20 (m, 2 H, Ph-H), 6.94–6.90 (m, 2 H, Ph-H), 128.6, 128.3, 126.6, 109.6, 82.4, 79.6, 79.4, 74.9, 68.4, 58.8,
5.10 (s, 2 H, OCH2Ph), 4.42 (pent, J = 6.4 Hz, 1 H, 4-H), 3.94 (dd,
J = 8.0, 6.0 Hz, 1 H, 5-Ha), 3.66 (t, J = 8.0 Hz, 1 H, 5-Hb), 3.08
[dd, J = 13.6, 6.0 Hz, 1 H, (o-OBn-C6H4)CHaH], 2.90 [dd, J =
13.6, 7.2 Hz, 1 H, (o-OBn-C6H4)CHHb], 1.43 (s, 3 H, -CH3), 1.35
(s, 3 H, -CH3) ppm.
27.1 ppm. IR (neat): ν = 3289, 2986, 2934, 2116, 1604, 1454, 1090,
˜
756 cm–1. C15H18O3 (246.31): calcd. C 73.15, H 7.37; found C
73.22, H 7.32.
Compound 9: Colourless solid, m.p. 172–174 °C; Rf = 0.39 in
EtOAc/hexanes (1:10, double elution). 1H NMR (400 MHz,
CDCl3): δ = 7.45 (d, J = 8.4 Hz, 2 H, Ar-H), 7.33 (d, J = 8.4 Hz,
General Procedure for (Ph3P)AuCl/AgSbF6-Catalysed Bicyclic Ace-
tal Formation: (PPh3)AuCl (0.0106 mmol, 2 mol-%) and AgSbF6 2 H, Ar-H), 5.24 (d, J = 5.2 Hz, 1 H, 7-H), 4.42 (d, J = 4.8 Hz, 1
(2 mol-%) were added consecutively to a solution of an epoxy al-
kyne (0.532 mmol) in dry acetone (2.5 mL). Precipitation of AgCl
as white solid was observed. The mixture was stirred at 60 °C. After
the completion of the reaction, solvent was removed under reduced
pressure and the residue was subjected to column chromatography
(EtOAc in hexanes 6–10%) to provide the pure product(s).
H, 1-H), 3.70 (d, J = 11.6 Hz, 1 H, 2-Ha), 3.65 (d, J = 11.2 Hz, 1
H, 4-Ha), 3.62 (d, J = 11.2 Hz, 1 H, 4-Hb), 3.28 (d, J = 11.6 Hz,
1 H, 2-Hb), 1.49 (s, 3 H, -CH3) ppm. 13C NMR (100 MHz, CDCl3):
δ = 135.6, 133.2, 128.3, 127.6, 105.9, 80.4, 78.3, 71.7, 64.2,
20.1 ppm. IR (neat): ν = 2961, 2920, 2856, 1490, 1068, 834,
˜
648 cm–1. C12H13ClO3 (240.69): calcd. C 59.88, H 5.44; found C
59.75, H 5.41.
Compound 4: Colourless semisolid; Rf = 0.46 in EtOAc/hexanes
1
(1:10, double elution). H NMR (400 MHz, CDCl3): δ = 7.51 (d,
Compound 10: Colourless semisolid; Rf = 0.25 in EtOAc/hexanes
1
J = 7.2 Hz, 2 H, Ph-H), 7.36 (t, J = 7.2 Hz, 2 H, Ph-H), 7.29 (d, J
= 7.2 Hz, 1 H, Ph-H), 5.29 (d, J = 4.8 Hz, 1 H, 7-H), 4.43 (d, J =
(1:10, double elution). H NMR (400 MHz, CDCl3): δ = 7.32 (d,
J = 9.2 Hz, 2 H, Ar-H), 7.30 (d, J = 9.2 Hz, 2 H, Ar-H), 5.34 (s, 1
4.4 Hz, 1 H, 1-H), 3.70 (d, J = 12.0 Hz, 1 H, 2-Ha), 3.68 (d, J = H, 7-H), 4.18 (s, 1 H, 1-H), 3.87 (d, J = 11.6 Hz, 1 H, 2-Ha), 3.78
10.8 Hz, 1 H, 4-Ha), 3.63 (d, J = 11.2 Hz, 1 H, 4-Hb), 3.31 (d, J (d, J = 11.6 Hz, 1 H, 2-Hb), 3.62 (s, 2 H, 4-H), 1.53 (s, 3 H,
= 12.0 Hz, 1 H, 2-Hb), 1.50 (s, 3 H, -CH3) ppm. 13C NMR -CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 140.4, 133.7, 128.6,
(100 MHz, CDCl3): δ = 137.1, 128.2, 127.5, 126.1, 105.8, 81.1, 78.5, 127.4, 106.5, 81.5, 79.8, 72.2, 68.2, 19.6 ppm. IR (neat): ν = 2924,
˜
71.8, 64.3, 20.2 ppm. IR (neat): ν = 2963, 1494, 1452, 1302, 1233, 1734, 1493, 1238, 826 cm–1. C12H13ClO3 (240.69): calcd. C 59.88,
˜
1063, 876, 700 cm–1. C12H14O3 (206.24): calcd. C 69.88, H 6.84;
found C 69.95, H 6.81.
H 5.44; found C 59.65, H 5.41.
Compound 12: Yellow solid, m.p. 135–137 °C; Rf = 0.47 in EtOAc/
hexanes (1:5, triple elution). 1H NMR (400 MHz, CDCl3): δ = 8.22
(d, J = 8.0 Hz, 2 H, Ar-H), 7.68 (d, J = 8.0 Hz, 2 H, Ar-H), 5.35
Compound 5: Colourless liquid; Rf = 0.33 in EtOAc/hexanes (1:10,
1
double elution). H NMR (400 MHz, CDCl3): δ = 7.39–7.26 (m, 5
H, Ph-H), 5.38 (s, 1 H, 7-H), 4.22 (s, 1 H, 1-H), 3.88 (d, J = (d, J = 4.8 Hz, 1 H, 7-H), 4.56 (d, J = 4.4 Hz, 1 H, 1-H), 3.73 (d,
11.6 Hz, 1 H, 2-Ha), 3.79 (d, J = 11.6 Hz, 1 H, 2-Hb), 3.64 (s, 2 J = 12.0 Hz, 1 H, 2-Ha), 3.67 (d, J = 11.2 Hz, 1 H, 4-Ha), 3.63 (d,
1564
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 1557–1569

Gold-Catalysed Activation of Epoxides
J = 11.2 Hz, 1 H, 4-Hb), 3.21 (d, J = 12.0 Hz, 1 H, 2-Hb), 1.52 (s,
1460, 1121, 824, 700, 563 cm–1. C13H16O3 (220.27): calcd. C 70.89,
3 H, -CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 147.2, 144.8, H 7.32; found C 70.80, H 7.22.
127.0, 123.4, 106.4, 80.1, 78.3, 71.6, 64.3, 19.9 ppm. IR (neat): ν =
˜
Compound 21: Colourless solid, m.p. 66–68 °C; Rf = 0.32 in EtOAc/
hexanes (1:3). 1H NMR (400 MHz, CDCl3): δ = 7.30 (t, J = 7.2 Hz,
2 H, Ph-H), 7.22–7.20 (m, 3 H, Ph-H), 4.48 (d, J = 4.8 Hz, 1 H, 7-
Ha), 4.17 (d, J = 6.4 Hz, 1 H, 7-Hb), 4.10 (d, J = 11.6 Hz, 1 H, 2-
Ha), 3.91 (dd, J = 6.0, 5.6 Hz, 1 H, 1-H), 3.74 (dd, J = 10.8, 3.6 Hz,
1 H, 4-H), 3.41 (d, J = 11.6 Hz, 1 H, 2-Hb), 3.17 (dd, J = 14.4,
10.8 Hz, 1 H, -CH2Ph), 2.77 (dd, J = 14.4, 3.6 Hz, 1 H, -CH2Ph),
1.44 (s, 3 H, -CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 138.5,
128.9, 128.4, 126.3, 106.9, 79.5, 75.4, 67.4, 63.4, 34.1, 20.7 ppm. IR
3293, 2922, 1728, 1520, 1346, 1074, 856 cm–1. C12H13NO5 (251.24):
calcd. C 57.37, H 5.22, N 5.58; found C 57.25, H 5.26, N 5.71.
Compound 13: Yellow semisolid; Rf = 0.37 in EtOAc/hexanes (1:5,
triple elution). 1H NMR (400 MHz, CDCl3): δ = 8.22 (d, J =
8.4 Hz, 2 H, Ar-H), 7.54 (d, J = 8.4 Hz, 2 H, Ar-H), 5.47 (s, 1 H,
7-H), 4.22 (s, 1 H, 1-H), 3.91 (d, J = 11.2 Hz, 1 H, 2-Ha), 3.82 (d,
J = 11.6 Hz, 1 H, 2-Hb), 3.65 (s, 2 H, 4-H), 1.52 (s, 3 H,
-CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 149.2, 147.7, 126.8,
(neat): ν = 2926, 1732, 1454, 1240, 860, 554 cm–1. C H O
˜
123.7, 107.1, 81.5, 79.4, 72.1, 68.2, 19.5 ppm. IR (neat): ν = 3293,
˜
13 16
3
2859, 1601, 1520, 1346, 1111, 857 cm–1. C12H13NO5 (251.24): calcd.
C 57.37, H 5.22, N 5.58; found C 57.45, H 5.16, N 5.51.
(220.27): calcd. C 70.89, H 7.32; found C 70.91, H 7.29.
Compound 24: Colourless heavy liquid; Rf = 0.45 in EtOAc/hexanes
1
(1:10). H NMR (400 MHz, CDCl3): δ = 4.38 (d, J = 4.0 Hz, 1 H,
Compound 15: Colourless solid, m.p. 56–58 °C; Rf = 0.53 in EtOAc/
hexanes (1:3, double elution). 1H NMR (400 MHz, CDCl3): δ =
7.50 (d, J = 7.2 Hz, 2 H, Ph-H), 7.35 (t, J = 7.2 Hz, 2 H, Ph-H),
7.28 (d, J = 7.6 Hz, 1 H, Ph-H), 5.29 (d, J = 4.4 Hz, 1 H, 7-H),
4.48 (d, J = 4.0 Hz, 1 H, 1-H), 4.21 (q, J = 7.2 Hz, 2 H,
-OCH2CH3), 3.87 (d, J = 11.2 Hz, 1 H, 2-Ha), 3.78 (d, J = 11.2 Hz,
1 H, 2-Hb), 3.73 (d, J = 11.6 Hz, 1 H, 4-Ha), 3.32 (d, J = 11.6 Hz,
1 H, 4-Hb), 2.86 (d, J = 14.8 Hz, 1 H, -COCHaH-), 2.82 (d, J =
7-Ha), 4.14 (d, J = 4.0 Hz, 1 H, 7-Hb), 3.89–3.86 (m, 2 H, 1-H, 2-
Ha), 3.64 (d, J = 12.0 Hz, 1 H, 2-Hb), 3.31 (s, 1 H, 4-H), 1.92 (brd,
J = 12.0 Hz, 1 H, Cy-H), 1.75–1.73 (m, 2 H, Cy-H), 1.62–1.61 (m,
1 H, Cy-H), 1.49–1.42 (m, 2 H, Cy-H), 1.37 (s, 3 H, -CH3), 1.27–
1.10 (m, 5 H, Cy-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 107.4,
85.0, 74.4, 70.1, 68.2, 39.2, 30.9, 27.0, 26.6, 26.4, 25.8, 20.2 ppm. IR
(neat): ν = 2936, 1722, 1453, 1382, 1227, 1098, 700 cm–1. C H O
˜
12 20
3
(212.29): calcd. C 67.89, H 9.50; found C 67.95, H 9.46.
14.8 Hz,
1 H, -COCHHb-), 1.30 (t, J = 7.2 Hz, 3 H,
-OCH2CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 168.2, 136.5,
Compound 25: Colourless liquid; Rf = 0.30 in EtOAc/hexanes
128.2, 127.6, 126.2, 104.8, 81.3, 78.7, 70.6, 64.4, 61.0, 40.4,
1
(1:10). H NMR (400 MHz, CDCl3): δ = 4.44 (d, J = 5.2 Hz, 1 H,
14.2 ppm. IR (neat): ν = 2964, 2866, 1730, 1452, 1190, 1055, 966,
˜
7-Ha), 4.14 (d, J = 6.4 Hz, 1 H, 7-Hb), 4.01 (d, J = 11.6 Hz, 1 H,
2-Ha), 3.87 (dd, J = 6.4, 5.2 Hz, 1 H, 1-H), 3.50 (d, J = 11.6 Hz,
1 H, 2-Hb), 3.23 (d, J = 4.8 Hz, 1 H, 4-H), 2.03 (brd, J = 8.0 Hz,
1 H, Cy-H), 1.80–1.72 (m, 2 H, Cy-H), 1.67–1.62 (m, 3 H, Cy-H),
1.44 (s, 3 H, -CH3), 1.34–1.26 (m, 2 H, Cy-H), 1.24–1.16 (m, 3 H,
Cy-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 107.4, 82.3, 74.9,
658 cm–1. C15H18O5 (278.30): calcd. C 64.74, H 6.52; found C
64.63, H 6.42.
Compound 16: Colourless heavy liquid; Rf = 0.45 in EtOAc/hexanes
1
(1:3, double elution). H NMR (400 MHz, CDCl3): δ = 7.38–7.27
(m, 5 H, Ph-H), 5.41 (s, 1 H, 7-H), 4.31 (s, 1 H, 1-H), 4.24–4.12
(m, 2 H, -CH2CH3), 3.91 (d, J = 11.6 Hz, 1 H, 2-Ha), 3.90 (d, J =
11.2 Hz, 1 H, 2-Hb), 3.82 (d, J = 11.2 Hz, 1 H, 4-Ha), 3.80 (d, J
= 11.2 Hz, 1 H, 4-Hb), 2.91 (d, J = 14.8 Hz, 1 H, -COCHaH-),
2.87 (d, J = 14.8 Hz, 1 H, -COCHHb-), 1.26 (t, J = 7.2 Hz, 3 H,
-CH2CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 168.3, 141.4,
128.6, 128.1, 126.2, 105.5, 81.8, 80.6, 71.2, 68.5, 61.2, 40.4,
67.0, 66.4, 39.6, 31.9, 28.8, 26.7, 26.6, 26.4, 21.6 ppm. IR (neat): ν
˜
= 2926, 1732, 1451, 1373, 1014 cm–1. C12H20O3 (212.29): calcd. C
67.89, H 9.50; found C 67.83, H 9.56.
Compound 28: Colourless semisolid; Rf = 0.33 in EtOAc/hexanes
(1:3). 1H NMR (400 MHz, CDCl3): δ = 3.89 (s, 1 H, -CH2CH),
3.86–3.77 (m, 2 H, -OCH2C), 3.53 (d, J = 10.8 Hz, 1 H, -CHCH2),
3.45 (d, J = 10.8 Hz, 1 H, -CHCH2), 2.00–1.97 (m, 2 H, Cy-H),
1.79–1.68 (m, 2 H, Cy-H), 1.62 (t, J = 3.2 Hz, 2 H, Cy-H), 1.45–
1.39 (m, 4 H, Cy-H), 1.36 (s, 3 H, -CH3) ppm. 13C NMR
(100 MHz, CDCl3): δ = 104.6, 82.8, 78.8, 72.0, 64.6, 37.5, 31.4,
14.2 ppm. IR (neat): ν = 2913, 2854, 1728, 1452, 1204, 1074, 870,
˜
700 cm–1. C15H18O5 (278.30): calcd. C 64.74, H 6.52; found C
64.47, H 6.47.
Compound 18:[20c] Colourless heavy liquid; Rf = 0.35 in EtOAc/
hexanes (1:5, double elution). 1H NMR (400 MHz, CDCl3): δ =
7.36–7.25 (m, 5 H, Ph-H), 4.54 (s, 2 H, -OCH2Ph), 4.51 (dd, J =
8.4, 5.6 Hz, 1 H, 7-H), 4.24 (s, 1 H, 1-H), 3.82 (d, J = 11.2 Hz, 1
H, 2-Ha), 3.61 (d, J = 11.2 Hz, 1 H, 2-Hb), 3.54–3.48 (m, 3 H, 4-
H, -OCH2CH-), 3.35 (dd, J = 9.2, 8.4 Hz, 1 H, -OCH2CH-), 1.34
(s, 3 H, -CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 138.0,
128.5, 127.84, 127.82, 105.6, 77.1, 76.8, 73.5, 72.3, 71.2, 68.2,
25.6, 24.2, 23.8, 21.0 ppm. IR (neat): ν = 3397, 2932, 2859, 1726,
˜
1451, 1377, 1161, 860 cm–1. C11H18O3 (198.26): calcd. C 66.64, H
9.15; found C 66.56, H 9.21.
Compound 30: Colourless liquid; Rf = 0.52 in EtOAc/hexanes (1:10,
double elution). 1H NMR (400 MHz, CDCl3): δ = 5.15 (t, J =
6.8 Hz, 1 H, -C=CHCH2-), 3.84 (d, J = 14.4 Hz, 1 H, 4-Ha), 3.80
(d, J = 14.4 Hz, 1 H, 4-Hb), 3.77 (s, 1 H, 1-H), 3.52 (d, J = 10.8 Hz,
1 H, 2-Ha), 3.44 (d, J = 10.8 Hz, 1 H, 2-Hb), 2.20–2.13 (m, 1 H,
-C=CHCH2CH2-), 2.11–1.99 (m, 2 H, -CCH2CH2-), 1.90–1.84 (m,
1 H, -C=CHCH2CH2-), 1.69 (s, 3 H, -CH3), 1.62 (s, 3 H, -CH3),
1.36 (s, 3 H, -CH3), 1.31 (s, 3 H, -CH3) ppm. 13C NMR (100 MHz,
CDCl3): δ = 131.7, 124.2, 105.0, 83.1, 80.7, 71.8, 64.8, 34.9, 25.6,
19.9 ppm. IR (neat): ν = 2861, 1723, 1452, 1381, 1236, 1115,
˜
739 cm–1. C14H18O4 (250.29): calcd. C 67.18, H 7.25; found C
67.22, H 7.21.
Compound 20: Colourless solid, m.p. 68–70 °C; Rf = 0.43 in EtOAc/
hexanes (1:3). 1H NMR (400 MHz, CDCl3): δ = 7.29 (t, J = 7.2 Hz,
2 H, Ph-H), 7.23 (d, J = 6.8 Hz, 2 H, Ph-H), 7.20 (d, J = 7.2 Hz,
1 H, Ph-H), 4.42 (d, J = 4.8 Hz, 1 H, 7-Ha), 4.23 (d, J = 6.4 Hz,
1 H, 7-Hb), 3.94 (dd, J = 6.0, 5.6 Hz, 1 H, 1-H), 3.85 (d, J =
25.4, 23.9, 20.8, 17.7 ppm. IR (neat): ν = 2965, 2922, 1454, 1373,
˜
1259, 864 cm–1. C13H22O3 (226.32): calcd. C 68.99, H 9.80; found
C 69.05, H 9.96.
11.6 Hz, 1 H, 2-Ha), 3.76 (dd, J = 9.6, 4.0 Hz, 1 H, 4-H), 3.62 (d, Compound 31: Colourless liquid; Rf = 0.44 in EtOAc/hexanes (1:10,
J = 11.2 Hz, 1 H, 2-Hb), 2.81 (dd, J = 14.4, 4.0 Hz, 1 H, -CH2Ph), double elution). 1H NMR (400 MHz, CDCl3): δ = 5.11 (t, J =
2.75 (dd, J = 14.4, 9.6 Hz, 1 H, -CH2Ph), 1.41 (s, 3 H, -CH3) ppm. 5.6 Hz, 1 H, -C=CHCH2-), 3.85 (s, 1 H, 1-H), 3.84 (d, J = 10.0 Hz,
13C NMR (100 MHz, CDCl3): δ = 138.5, 129.2, 128.3, 126.3, 106.9, 1 H, 4-Ha), 3.80 (d, J = 12.0 Hz, 1 H, 4-Hb), 3.54 (d, J = 10.8 Hz,
81.2, 74.5, 69.6, 68.2, 37.3, 20.2 ppm. IR (neat): ν = 2928, 1732, 1 H, 2-Ha), 3.47 (d, J = 10.8 Hz, 1 H, 2-Hb), 2.10–1.98 (m, 2 H,
˜
Eur. J. Org. Chem. 2011, 1557–1569
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1565

R. Balamurugan, R. B. Kothapalli, G. K. Thota
FULL PAPER
-C=CHCH2CH2-), 1.68 (s, 3 H, -CH3), 1.62 (s, 3 H, -CH3), 1.60– 7.6 Hz, 2 H, Ph-H), 7.36 (t, J = 7.6 Hz, 2 H, Ph-H), 7.29 (d, J =
1.58 (m, 2 H, -CCH2CH2-), 1.36 (s, 3 H, -CH3), 1.26 (s, 3 H, 7.2 Hz, 1 H, Ph-H), 5.29 (d, J = 4.8 Hz, 1 H, 7-H), 4.44 (d, J =
-CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 131.7, 124.2, 105.0, 4.8 Hz, 1 H, 1-H), 3.71 (d, J = 12.4 Hz, 1 H, 2-Ha), 3.68 (d, J =
83.0, 79.5, 71.8, 65.7, 31.9, 25.6, 23.2, 20.5, 19.1, 14.1 ppm. IR 11.2 Hz, 1 H, 4-Ha), 3.63 (d, J = 11.2 Hz, 1 H, 4-Hb), 3.31 (d, J
(neat): ν = 2965, 2922, 1454, 1373, 1259, 864 cm–1. C H O
= 11.6 Hz, 1 H, 2-Hb), 1.50 (s, 3 H, -CH3) ppm. C12H14O3 (206.24):
˜
13 22
3
(226.32): calcd. C 68.99, H 9.80; found C 68.91, H 9.85.
calcd. C 69.88, H 6.84; found C 69.75, H 6.91.
Compound 42: Colourless liquid; [α]2D5 = –19.8 (c = 0.23, CHCl3,
92% ee). 1H NMR (400 MHz, CDCl3): δ = 7.37–7.28 (m, 5 H, Ph-
H), 5.38 (s, 1 H, 7-H), 4.22 (s, 1 H, 1-H), 3.88 (d, J = 11.6 Hz, 1
H, 2-Ha), 3.79 (d, J = 11.6 Hz, 1 H, 2-Hb), 3.64 (s, 2 H, 4-H), 1.55
(s, 3 H, -CH3) ppm. C12H14O3 (206.24): calcd. C 69.88, H 6.84;
found C 69.78, H 6.82.
Compound 44: Colourless semisolid; [α]2D5 = +132.5 (c = 0.85,
CHCl3, 91% ee). 1H NMR (400 MHz, CDCl3): δ = 7.51 (d, J =
7.6 Hz, 2 H, Ph-H), 7.36 (t, J = 7.6 Hz, 2 H, Ph-H), 7.29 (d, J =
7.6 Hz, 1 H, Ph-H), 5.29 (d, J = 4.4 Hz, 1 H, 7-H), 4.44 (d, J =
4.4 Hz, 1 H, 1-H), 3.71 (d, J = 12.0 Hz, 1 H, 2-Ha), 3.68 (d, J =
11.2 Hz, 1 H, 4-Ha), 3.63 (d, J = 10.8 Hz, 1 H, 4-Hb), 3.31 (d, J
= 11.6 Hz, 1 H, 2-Hb), 1.50 (s, 3 H, -CH3) ppm. C12H14O3 (206.24):
calcd. C 69.88, H 6.84; found C 69.81, H 6.82.
Compound 45: Colourless liquid; [α]2D5 = +24.1 (c = 1.98, CHCl3,
90% ee). 1H NMR (400 MHz, CDCl3): δ = 7.38–7.27 (m, 5 H, Ph-
H), 5.37 (s, 1 H, 7-H), 4.20 (s, 1 H, 1-H), 3.86 (d, J = 11.6 Hz, 1
H, 2-Ha), 3.78 (d, J = 11.6 Hz, 1 H, 2-Hb), 3.62 (s, 2 H, 4-H), 1.54
(s, 3 H, -CH3) ppm. C12H14O3 (206.24): calcd. C 69.88, H 6.84;
found C 69.92, H 6.79.
Compound 33: Colourless liquid; Rf = 0.67 in EtOAc/hexanes (1:10,
double elution). 1H NMR (400 MHz, CDCl3): δ = 7.57 (d, J =
7.6 Hz, 2 H, Ph-H), 7.35 (t, J = 7.6 Hz, 2 H, Ph-H), 7.30 (d, J =
7.2 Hz, 1 H, Ph-H), 4.78 (s, 1 H, 7-H), 3.7 0 (d, J = 10.8 Hz, 1 H,
4-Ha), 3.58 (d, J = 10.8 Hz, 1 H, 4-Hb), 3.41 (d, J = 11.6 Hz, 1 H,
2-Ha), 3.24 (d, J = 11.6 Hz, 1 H, 2-Hb), 1.48 (s, 3 H, -CH3), 1.30
(s, 3 H, -CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 136.5,
128.1, 127.7, 126.5, 105.0, 86.6, 82.3, 70.7, 68.5, 20.3, 17.8 ppm. IR
(neat): ν = 2978, 2853, 1605, 1452, 1379, 1223, 1103, 824, 700 cm–1.
˜
C13H16O3 (220.27): calcd. C 70.89, H 7.32; found C 70.92, H 7.33.
Compound 34: Colourless liquid; Rf = 0.58 in EtOAc/hexanes (1:10,
1
double elution). H NMR (400 MHz, CDCl3): δ = 7.36–7.28 (m, 5
H, Ph-H), 5.25 (s, 1 H, 7-H), 3.70 (d, J = 10.8 Hz, 1 H, 2-Ha), 3.65
(d, J = 11.2 Hz, 1 H, 4-Ha), 3.64 (d, J = 11.2 Hz, 1 H, 4-Hb), 3.56
(d, J = 11.2 Hz, 1 H, 2-Hb), 1.56 (s, 3 H, -CH3), 0.74 (s, 3 H,
-CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 140.1, 128.2, 128.0,
127.2, 105.3, 83.5, 82.5, 73.7, 71.4, 19.6, 17.5 ppm. IR (neat): ν =
˜
2934, 2851, 1716, 1454, 1227, 1098, 1018, 868 cm–1. C13H16O3
(220.27): calcd. C 70.89, H 7.32; found C 70.83, H 7.41.
Compound 36: Colourless liquid; Rf = 0.46 in EtOAc/hexanes (1:10,
double elution). 1H NMR (400 MHz, CDCl3): δ = 7.48 (d, J =
7.2 Hz, 2 H, Ph-H), 7.36 (t, J = 7.6 Hz, 2 H, Ph-H), 7.28 (d, J =
7.2 Hz, 1 H, Ph-H), 5.18 (d, J = 5.2 Hz, 1 H, 8-H), 4.38 (dd, J =
5.6, 2.4 Hz, 1 H, 1-H), 3.97 (dd, J = 12.4, 6.4 Hz, 1 H, 4-Ha), 3.75
(td, J = 12.4, 4.4 Hz, 1 H, 4-Hb), 3.45 (d, J = 13.2 Hz, 1 H, 2-Ha),
3.39 (dd, J = 13.2, 2.4 Hz, 1 H, 2-Hb), 2.49 (ddd, J = 14.4, 12.0,
6.4 Hz, 1 H, 5-Ha), 1.90 (dd, J = 14.4, 4.0 Hz, 1 H, 5-Hb), 1.59 (s,
3 H, -CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 136.4, 128.2,
127.6, 126.8, 110.7, 82.0, 79.6, 70.7, 68.2, 42.3, 27.5 ppm. IR (neat):
Compound 46: Colourless liquid; Rf = 0.38 in EtOAc/hexanes (1:5).
1H NMR (400 MHz, CDCl3): δ = 7.50 (d, J = 7.6 Hz, 2 H, Ph-H),
7.36 (t, J = 7.6 Hz, 2 H, Ph-H), 7.29 (d, J = 7.2 Hz, 1 H, Ph-H),
5.29 (d, J = 4.4 Hz, 1 H, 7-H), 4.48 (d, J = 4.4 Hz, 1 H, 1-H), 4.21
(q, J = 7.2 Hz, 2 H, OCH2CH3), 3.87 (d, J = 11.2 Hz, 1 H, 2-Ha),
3.78 (d, J = 11.2 Hz, 1 H, 2-Hb), 3.73 (d, J = 12.0 Hz, 1 H, 4-Ha),
3.32 (d, J = 12.0 Hz, 1 H, 4-Hb), 1.30 (t, J = 7.2 Hz, 3 H,
-OCH2CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 168.2, 136.4,
128.2, 127.5, 126.1, 104.7, 81.2, 78.6, 70.5, 64.3, 61.0, 40.0–39.5
(m, -CD ), 14.2 ppm. IR (neat): ν = 2984, 1730, 1451, 1271, 849,
˜
ν = 3412, 2930, 1715, 1452, 1377, 1173, 700 cm–1. C H O
2
˜
13 16
3
700 cm–1. C15H16D2O5 (280.32): calcd. C 64.27, H 7.19; found C
(220.27): calcd. C 70.89, H 7.32; found C 70.85, H 7.36.
64.32, H 7.21.
Compound 37: Colourless liquid; Rf = 0.38 in EtOAc/hexanes (1:10,
Compound 47: Colourless liquid; Rf = 0.24 in EtOAc/hexanes (1:5).
1H NMR (400 MHz, CDCl3): δ = 7.36–7.29 (m, 5 H, Ph-H), 5.41
(s, 1 H, 7-H), 4.31 (s, 1 H, 1-H), 4.22–4.15 (m, 2 H, -OCH2CH3),
3.91 (d, J = 11.6 Hz, 1 H, 2-Ha), 3.89 (d, J = 11.6 Hz, 1 H, 2-Hb),
3.81 (d, J = 11.2 Hz, 1 H, 4-Ha), 3.80 (d, J = 11.6 Hz, 1 H, 4-Hb),
1.28 (t, J = 7.2 Hz, 3 H, -OCH2CH3) ppm. 13C NMR (100 MHz,
CDCl3): δ = 168.2, 141.2, 128.5, 128.0, 126.1, 105.3, 81.7, 80.5,
1
double elution). H NMR (400 MHz, CDCl3): δ = 7.39–7.27 (m, 5
H, Ph-H), 5.09 (d, J = 3.2 Hz, 1 H, 8-H), 4.26 (d, J = 3.2 Hz, 1 H,
1-H), 3.95–3.91 (m, 1 H, 4-Ha), 3.89 (d, J = 12.4 Hz, 1 H, 2-Ha),
3.72 (dd, J = 12.8, 1.6 Hz, 1 H, 2-Hb), 3.66 (td, J = 12.4, 3.2 Hz,
1 H, 4-Hb), 2.36 (ddd, J = 15.2, 12.0, 5.2 Hz, 1 H, 5-Ha), 2.00 (dt,
J = 15.2, 3.6 Hz, 1 H, 5-Hb), 1.67 (s, 3 H, -CH3) ppm. 13C NMR
(100 MHz, CDCl3): δ = 141.9, 128.6, 127.9, 126.1, 111.2, 85.8, 78.4,
71.1, 68.3, 61.1, 40.2–39.3 (m, -CD ), 14.1 ppm. IR (neat): ν =
˜
2
73.7, 67.9, 44.1, 27.5 ppm. IR (neat): ν = 2920, 1736, 1456, 1379,
˜
2984, 2054, 1734, 1452, 1267, 1061, 739 cm–1. C15H16D2O5
1196, 698 cm–1. C13H16O3 (220.27): calcd. C 70.89, H 7.32; found
C 70.93, H 7.25.
(280.32): calcd. C 64.27, H 7.19; found C 64.15, H 7.22.
Compound 48a: cis Isomer; colourless liquid; Rf = 0.70 in EtOAc/
hexanes (1:10, four elutions). 1H NMR (400 MHz, CDCl3): δ =
7.39–7.27 (m, 5 H, Ph-H), 5.28 (d, J = 7.2 Hz, 1 H, -CHPh), 4.58–
4.54 (m, 1 H, -OCH2CH-), 4.22 (q, J = 7.2 Hz, 2 H, -CO2CH2CH3),
4.01 (s, 2 H, -OCH2CC-), 3.18 (dd, J = 9.2, 8.4 Hz, 1 H, -OCH2-
CH-), 3.02 (dd, J = 9.6, 3.6 Hz, 1 H, -OCH2CH-), 1.29 (t, J =
7.2 Hz, 3 H, -CO2CH2CH3) ppm. 13C NMR (100 MHz, CDCl3): δ
= 153.0, 136.8, 128.2, 128.0, 126.6, 108.9, 82.7, 78.5, 78.0, 77.3,
70.5, 62.0, 58.0, 26.2 (septet, J = 20.0 Hz, -CD3), 23.8 (septet, J =
Compound 39: Colourless liquid; Rf = 0.68 in EtOAc/hexanes (1:3).
1H NMR (400 MHz): δ = 4.51 (m, 1 H, 1-Ha), 4.27–4.12 (m, 4 H,
-OCH2CH3), 4.05 (d, J = 6.8 Hz, 1 H, 7-Ha), 3.66 (t, J = 5.2 Hz,
1 H, 7-Hb), 2.65 (d, J = 14.4 Hz, 1 H, 4-Ha), 2.60 (d, J = 14.4 Hz,
1 H, 2-Ha), 2.32 (d, J = 14.0 Hz, 1 H, 4-Hb), 2.04 (dd, J = 14.4,
4.0 Hz, 1 H, 2-Hb), 1.47 (s, 3 H, -CH3), 1.27 (t, J = 7.2 Hz, 3 H,
-OCH2CH3), 1.22 (t, J = 6.8 Hz, 3 H, -OCH2CH3) ppm. 13C NMR
(100 MHz, CDCl3): δ = 171.3, 170.9, 105.3, 73.8, 68.6, 61.85, 61.82,
51.6, 40.5, 31.8, 24.2, 14.0, 13.9 ppm. IR (neat): ν = 2984, 1734,
˜
20.0 Hz, -CD ), 13.9 ppm. IR (neat): ν = 2910, 2240, 1715, 1454,
˜
3
1123, 858 cm–1. C13H20O6 (272.30): calcd. C 57.34, H 7.40; found
C 57.45, H 7.36.
1366, 1250, 750 cm–1. Calcd. for C18H16D6O5: C 66.64, H 8.70;
found C, 66.75, H 8.75.
Compound 41: Colourless semisolid; [α]2D5 = –134.9 (c = 0.42,
CHCl3, 92% ee). 1H NMR (400 MHz, CDCl3): δ = 7.51 (d, J =
Compound 48b: trans Isomer; colourless liquid; Rf = 0.74 in EtOAc/
hexanes (1:10, four elutions). 1H NMR (400 MHz, CDCl3): δ =
1566
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 1557–1569

Gold-Catalysed Activation of Epoxides
7.41–7.31 (m, 5 H, Ph-H), 4.83 (d, J = 8.4 Hz, 1 H, -CHPh), 4.41
(d, J = 16.8 Hz, 1 H, -OCH2CC-), 4.32 (d, J = 16.8 Hz, 1 H,
C-), 4.157 (d, J = 2.4 Hz, 1 H, -OCH2C-), 4.02–3.98 (m, 1 H,
-OCH2CH-), 3.88–3.83 (m, 1 H, -OCH2CH-), 3.63 (dd, J = 9.6,
-OCH2CC-), 4.25 (q, J = 7.2 Hz, 2 H, -CO2CH2CH3), 3.98 (dt, J 6.4 Hz, 1 H, -OCH2CH-), 3.55 (dd, J = 5.2, 3.6 Hz, 1 H,
= 8.4, 4.0 Hz, 1 H, -OCH2CH-), 3.75–3.68 (m, 2 H, -OCH2CH-), -OCH2CH-), 3.53 (dd, J = 5.2, 3.6 Hz, 1 H, -OCH2CH-), 3.49 (dd,
1.32 (t, J = 7.2 Hz, 3 H, -CO2CH2CH3) ppm. 13C NMR (100 MHz,
CDCl3): δ = 153.0, 137.5, 128.6, 128.3, 126.5, 109.4, 82.7, 82.2,
79.3, 78.4, 68.7, 62.1, 58.5, 26.6–25.5 [m,(-CD3)2], 14.0 ppm. IR
J = 9.6, 5.2 Hz, 1 H, -OCH2CH-), 2.92 (d, J = 2.8 Hz, 1 H, -CH-
OH), 2.82 (d, J = 4.4 Hz, 1 H, -CH-OH), 2.70 (d, J = 5.2 Hz, 1
H, -CH-OH), 2.56 (d, J = 4.8 Hz, 1 H, -CH-OH), 2.44 (t, J =
2.0 Hz, 1 H, -CCH), 2.436 (t, J = 2.4 Hz, 1 H, -CCH) ppm. 13C
NMR (100 MHz, CDCl3): δ = 140.3, 140.0, 128.37, 128.36, 127.9,
127.7, 126.7, 126.2, 79.1, 75.01, 75.00, 74.8, 74.6, 74.4, 73.4, 70.5,
(neat): ν = 2905, 2239, 1715, 1454, 1366, 1252, 1068, 750 cm–1.
˜
Calcd. for C18H16D6O5: C 66.64, H 8.70; found C, 66.75, H 8.67.
Compounds 49a and 49b: AuCl3 (9 mg, 2 mol-%) was added under
N2 to a solution of the epoxy alkyne 14 (374 mg, 1.437 mmol) in
acetone (10 mL). After the system had been stirred for 10 min at
room temperature, solvent was removed. The crude product was
purified by column chromatography (EtOAc/hexanes 1:13) to sepa-
rate 49a (cis isomer, 206 mg, 45%) and 49b (trans isomer, 192 mg,
42%).
70.2, 58.6, 58.5 ppm. IR (neat): ν = 3453, 2915, 2116, 1495, 1454,
˜
1099 cm–1. Calcd. for C12H14O3: C 69.88, H 6.84; found C, 69.75,
H 6.91.
Compounds 52a and 52b: PTSA (120 mg, 40 mol-%) was added to
a solution of the diol 54 (300 mg, 1.587 mmol) in dichloromethane
(10 mL). Triethyl orthoformate (0.39 mL, 2.38 mmol) was then
added slowly. After the system had been stirred for 0.5 h at room
temperature, 1,3-diphenylpropan-2-one (267 mg, 1.27 mmol) was
added and the stirring was continued at room temperature for 3 h.
The reaction mixture was then washed with aqueous sodium hydro-
gen carbonate solution and saturated aqueous brine, dried with
anhydrous Na2SO4, concentrated and purified by column
chromatography (EtOAc/hexanes 1:20) as a colourless liquid (trans,
156 mg; cis, 246 mg; 80%; cis/ trans = 1.58:1).
Compound 49a: Colourless liquid; Rf = 0.48 in EtOAc/hexanes
1
(1:10, three elutions). H NMR (400 MHz, CDCl3): δ = 7.37–7.29
(m, 5 H, Ph-H), 5.28 (d, J = 7.2 Hz, 1 H, -CHPh), 4.59–4.54 (m,
1 H, -OCH2CH-), 4.22 (q, J = 7.2 Hz, 2 H, -CO2CH2CH3), 4.01
(s, 2 H, -OCH2CC-), 3.18 (dd, J = 9.6, 8.0 Hz, 1 H, -OCH2CH-),
3.02 (dd, J = 10.0, 4.0 Hz, 1 H, - OCH2CH-), 1.66 (s, 3 H, -CH3),
1.48 (s, 3 H, -CH3), 1.30 (t, J = 7.2 Hz, 3 H, -CO2CH2CH3) ppm.
13C NMR (100 MHz, CDCl3): δ = 153.0, 136.7, 128.2, 128.0, 126.6,
109.1, 82.7, 78.5, 78.1, 77.2, 70.5, 62.0, 58.0, 27.1, 24.7, 13.9 ppm.
Compound 52a: Colourless liquid; Rf = 0.50 in EtOAc/hexanes
(1:10, double elution). 1H NMR (400 MHz, CDCl3): δ = 7.34–7.20
(m, 13 H, Ph-H), 6.88–6.86 (m, 2 H, Ph-H), 4.84 (d, J = 7.6 Hz, 1
H, PhCH-), 4.34 (dt, J = 11.2, 4.4 Hz, 1 H, -OCH2CH-), 3.71 (d,
J = 15.6 Hz, 1 H, -OCH2C-), 3.63 (d, J = 15.6 Hz, 1 H, -OCH2-
C-), 3.12–3.04 (m, 3 H, PhCH2C-), 2.98 (d, J = 14.0 Hz, 1 H,
PhCH2C-), 2.60 (dd, J = 9.2, 8.4 Hz, 1 H, -OCH2CH-), 2.46 (dd,
IR (neat): ν = 2988, 2936, 2238, 1713, 1454, 1379, 864, 741 cm–1.
˜
Calcd. for C18H22O5: C 67.91, H 6.97; found C, 68.12, H 6.91.
Compound 49b: Colourless liquid; Rf = 0.56 in EtOAc/hexanes
1
(1:10, three elution). H NMR (400 MHz, CDCl3): δ = 7.41–7.32
(m, 5 H, Ph-H), 4.83 (d, J = 8.4 Hz, 1 H, -CHPh), 4.40 (d, J =
16.8 Hz, 1 H, -OCH2CC-), 4.32 (d, J = 16.8 Hz, 1 H, -OCH2-
CC-), 4.24 (q, J = 7.2 Hz, 2 H, - CO2CH2CH3), 3.93–3.95 (m, 1
H, -OCH2CH-), 3.75–3.68 (m, 2 H, - OCH2CH-), 1.57 (s, 3 H,
J = 9.6, 4.0 Hz, 1 H, -OCH2CH-), 2.24 (brs, 1 H, -CCH) ppm. 13
C
NMR (100 MHz, CDCl3): δ = 136.6, 136.04, 136.00, 131.4, 130.6,
128.1, 128.0, 127.8, 127.7, 126.5, 111.3, 79.3, 79.0, 77.8, 74.2, 70.0,
-CH3), 1.53 (s,
3 H, -CH3), 1.31 (t, J = 7.2 Hz, 3 H,
58.0, 44.14, 44.10 ppm. IR (neat): ν = 3293, 2926, 2117, 1721, 1601,
˜
-CO2CH2CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 153.0,
1454 cm–1. Calcd. for C27H26O3: C 81.38, H 6.58; found C, 81.22,
H 6.67.
137.5, 128.6, 128.3, 126.5, 109.6, 82.7, 82.2, 79.3, 78.4, 68.7, 62.1,
58.5, 27.0, 13.9 ppm. IR (neat): ν = 2986, 2934, 2238, 1714, 1454,
˜
1371, 1252, 868, 752 cm–1. Calcd. for C18H22O5: C 67.91, H 6.97;
found C, 67.85, H 7.05.
Compound 52b: Colourless liquid; Rf = 0.64 in EtOAc/hexanes
(1:10, double elution). 1H NMR (400 MHz, CDCl3): δ = 7.38–7.18
(m, 13 H, Ph-H), 6.84 (d, J = 7.2 Hz, 2 H, Ph-H), 4.17 (d, J =
16.0 Hz, 1 H, -OCH2C-), 4.12 (d, J = 16.0 Hz, 1 H, -OCH2C-),
3.98 (d, J = 9.2 Hz, 1 H, Ph-CH-), 3.55 (dt, J = 9.2, 3.2 Hz, 1 H,
-OCH2CH-), 3.35–3.31 (m, 2 H, PhCH2C-), 3.18 (d, J = 14.0 Hz,
1 H, -OCH2C-), 3.10–3.04 (m, 3 H, -OCH2C-, PhCH2C-), 2.41
(brs, 1 H, -CCH) ppm. 13C NMR (100 MHz, CDCl3): δ = 136.6,
136.4, 136.3, 131.24, 131.20, 129.5, 128.4, 128.3, 128.0, 127.9,
127.2, 126.5, 111.6, 82.3, 80.2, 79.4, 74.7, 68.3, 58.4, 45.5,
Compound 50: 1H NMR (400 MHz, CDCl3): δ = 7.51 (d, J =
7.6 Hz, 2 H, Ph-H), 7.36 (t, J = 7.2 Hz, 2 H, Ph-H), 7.29 (d, J =
7.2 Hz, 1 H, Ph-H), 5.29 (d, J = 4.8 Hz, 1 H, 7-H), 4.44 (d, J =
4.8 Hz, 1 H, 1-H), 3.71 (d, J = 11.6 Hz, 1 H, 2-Ha), 3.66–6.61 (m,
1 H, 4-H), 3.31 (d, J = 11.6 Hz, 1 H, 2-Hb), 1.50–1.47 (m, 1 H,
-CHD2) ppm. 13C NMR (100 MHz, CDCl3): δ = 137.0, 128.2,
127.4, 126.1, 105.7, 81.0, 78.4, 71.7, 71.6 (m), 64.2, 20.1–19.6
(m) ppm. IR (neat): ν = 2963, 2857, 1605, 1495, 1059, 1233 cm–1.
˜
45.0 ppm. IR (neat): ν = 3057, 2924, 2117, 1716, 1495, 1454, 1265,
˜
Compound 51: 1H NMR (400 MHz, CDCl3): δ = 7.37–7.30 (m, 5 H,
Ph-H), 5.38 (s, 1 H, 7-H), 4.22 (s, 1 H, 1-H), 3.88 (d, J = 11.2 Hz, 1
H, 2-Ha), 3.79 (d, J = 11.6 Hz, 1 H, 2-Hb), 3.64 (s, 2 H, 4-H),
1.55–1.52 (m, 1 H, -CHD2) ppm. 13C NMR (100 MHz, CDCl3): δ
= 142.0, 128.5, 128.0, 126.1, 106.4, 81.6, 80.5, 72.3, 68.4, 19.6–19.1
748 cm–1. Calcd. for C27H26O3: C 81.38, H 6.58; found C, 81.56,
H 6.67.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures, analytical and spectral characterisa-
tion data of the starting materials and important crystal parameters
and ORTEP diagrams of compounds 12 and 20.
(m) ppm. IR (neat): ν = 3436, 2911, 1452, 1240, 1009, 872 cm–1.
˜
Compound 54: The epoxy alkyne 3 (1900 mg, 10.1 mmol) was
heated at 60 °C in distilled water for 3 h.[29] The product was then
extracted into ethyl acetate and purified by column chromatog-
raphy (EtOAc/hexanes 1:3) as a colourless heavy liquid (yield 98%,
cis/trans 1:1.1). 1H NMR (400 MHz, CDCl3): δ = 7.38–7.31 (m, 10
H, Ph-H), 4.88 (t, J = 4.8 Hz, 1 H, Ph-CH-), 4.73 (dd, J = 6.8,
2.8 Hz, 1 H, Ph-CH-), 4.18 (d, J = 2.4 Hz, 1 H, -OCH2C-), 4.17
Acknowledgments
This work was funded by Department of Science and Technology
(DST), India. R. B. K. and G. K. T. thank the Council of Scientific
and Industrial Research (CSIR) and the University Grants Com-
(d, J = 2.0 Hz, 1 H, -OCH2C-), 4.160 (d, J = 2.0 Hz, 1 H, -OCH2- mission (UGC), India for fellowships.
Eur. J. Org. Chem. 2011, 1557–1569
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1567

R. Balamurugan, R. B. Kothapalli, G. K. Thota
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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CCDC-790338 (for 12) and -790339 (for 20) contain the sup-
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Received: August 27, 2010
Published Online: January 28, 2011
Eur. J. Org. Chem. 2011, 1557–1569
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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