Gold catalysed cyclisation reactions of 1,6-diynes triggered by the addition of methanol

Article abstract of DOI:10.1016/j.tet.2010.07.071

Further investigations on our recently discovered gold catalysed cyclisation reaction of 1,6-diynes are reported. By varying the steric and electronic nature of the alkyne substituents, the potentials and limitations of the new reaction have been identifi

Full text of DOI:10.1016/j.tet.2010.07.071

Tetrahedron 66 (2010) 7749e7754
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Tetrahedron
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Gold catalysed cyclisation reactions of 1,6-diynes triggered by the addition
of methanol
*
Christian Sperger, Lilian H.S. Strand, Anne Fiksdahl
Department of Chemistry, Sem Saelands v. 8, Norwegian University of Science and Technology, NTNU, 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:
Further investigations on our recently discovered gold catalysed cyclisation reaction of 1,6-diynes are
reported. By varying the steric and electronic nature of the alkyne substituents, the potentials and
limitations of the new reaction have been identified.
Received 24 March 2010
Received in revised form 5 July 2010
Accepted 26 July 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Available online 1 August 2010
Keywords:
Gold catalysis
Cyclisation
1,6-Diyne
1. Introduction
and subsequent cyclisation after final activation of the remaining
alkyne-moiety.
Gold catalysis of organic reactions has become a rapidly
expanding field in very recent years.1e3 Gold catalysts interact with
p
O
O
E
O
R1
R2
R1
R2
E
E
E
E
AuCl(L), AgSbF6
MeOH
-systems to activate multiple carbonecarbon bonds for nucleo-
E
E
philic attack. Gold catalysed hydration reactions of alkynes are well
known. Chabanas et al. reported the addition of alcohols to alkynes,
catalysed by different gold(I)-catalysts in the presence of an acid as
a cocatalyst.4 Depending on the alkyne substrate acetals or enol
ethers were formed. Tanaka et al. treated a number of alkynes in
a methanol-water mixture with a (PPh3)AuCH3/Hþ catalytic system
to form the respective ketones.5 The application of NHCegold
catalysts for alkyne hydration reactions has recently been repor-
ted.6 A gold catalysed cycloisomerisationehydroalkoxylation re-
action of homopropargylic alcohols has been demonstrated to form
the respective cyclic acetals.7 Alcohols have further been used in
gold catalysed alkoxycyclisations of 1,6-enynes to trap cationic
intermediates.8,9
E
H
I
II
III
E = COOMe
R1, R2 = Me, Et, C6H5 R1 = Me, R2 = H R1 = R2 = H
Scheme 1. Cyclisation reactions of 1,6-diynes.
The previous study was carried out on Me-, Et- and phenyl-
substituted diynes, as well as terminal alkynes. We hereby present
the results from further studies on gold catalysed cyclisation re-
actions of 1,6-diynes, varying the steric and electronic nature of the
alkyne substituents. Our results of the investigations in order to
identify the potentials and limitations of the new reaction, in-
cluding both goldeNHC and goldephosphine catalysts, are dis-
cussed below.
We have previously reported a new gold catalysed cyclisation
reaction of disubstituted 1,6-diynes10, providing stereoselectively
Z-cyclopentylidene derivatives (I) (Scheme 1). Mono- and di-ter-
minal 1,6-diynes afforded
a,b-unsaturated cyclopentene (II) and
2. Results and discussion
cyclohexenone (III) products. Plausible reaction mechanisms were
proposed for the formation of the products, including initial alkyne
activation by the gold complex, nucleophilic addition of methanol
2.1. Preparation of 1,6-diyne substrates
The malonate based 1,6-diynes 3aeg and 6aeb were readily
prepared by the procedures shown in Scheme 2. Unsymmetrically
substituted diynes 3aeb and 6a were obtained by stepwise malo-
nate alkylation with propargylbromides in 68e89% yield. The
* Correspondingauthor. E-mail address: anne.fiksdahl@chem.ntnu.no (A. Fiksdahl).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.07.071

7750
C. Sperger et al. / Tetrahedron 66 (2010) 7749e7754
TMSesubstituted diyne 3c was prepared by silylation of the ter-
minal alkyne 3b via the corresponding lithium acetylide in 44%
yield. Sonogashira cross-coupling of the terminal alkyne 3b with
the appropriate arylbromides gave access to the aryl substituted
1,6-diynes 3deg in 55e83% yield. The symmetrically substituted t-
Bu-malonate 6b was directly obtained by di-alkylation of 4 (85%).
A possible cyclisation of the alternative sterically demanding
TMSealkyne substrate 3c was attempted, as the SieC bond length
is in general larger than the equivalent CeC bond.11 However, by
goldephosphine catalysis, desilylation took place and the terminal
alkyne 3b was formed, together with the monohydration product
9c (Table 1, entry 3). In order to avoid desilylation, which is known
to occur under hydrolytic conditions, the reaction was repeated at
ꢀ20 ꢁC. However, no conversion of 3c took place after 1 h and rapid
desilylation was observed upon warming to 0 ꢁC. Correspondingly,
no reaction took place in the presence of AuCl(IMes) at 0 ꢁC, but
when heated to room temperature, instant desilylation occurred
(Table 1, entry 4). According to the literature12, it is also conceivable,
that the silver additive may catalyse the TMS-cleavage.
E
E
R1
E
E
R1
R2
E
E
NaH
NaH
R1
R2
H
Br
Br
1
(E = CO2Me)
2
5
(68%): E = CO2Me, R = Me, R2 = tBu
(88%): E = CO2Me, R1 = Me
1
4
3a
6a
(75%): E = CO2tBu, R1 = Et, R2 = Me
(65%): E = CO2tBu, R1 = Et
(E = CO2tBu)
6b (85%): E = CO2tBu, R1 = R2 = Me
4
(from
)
Modification of diyne substrates to include electron-with-
drawing substituents was afforded by introducing the p-cyano-
phenyl-(3d) and 2-pyridyl-substituent (3e). However, no
conversion of these 1,6-diyne substrates 3d and 3e was observed,
even upon heating to 50 ꢁC for several hours (Table 1, entries 5e8).
The electron-withdrawing properties of such substituents might
explain the missing ability of the electrophilic gold species to co-
ordinate to the respective triple bond. However, this does not ex-
plain the lack of hydration of the methyl substituted alkyne-moiety
to provide the expected ketone products 9dee.
To study whether a potential coordination of the nitrile or the
pyridyl groups would deactivate the gold catalyst, supplementary
cyclisation experiments with the dimethyl-substituted diyne 3i,
AuCl(PEt3) and AgSbF6 were performed in the presence of one
equivalent of benzonitrile or pyridine, respectively. According to
GC, the reaction was not hampered by the addition of benzonitrile
and full conversion of 3i was observed within 3 h at room tem-
perature. Further more, the commercial available, bulky gold-
ephosphine catalyst 13 (Scheme 4) shows high catalytic activity
although acetonitrile is coordinated to the metal centre. On the
other hand, the alkyne-moiety in 3d may act as an electron donor,
increasing the electron density of the aryl group and hence the
ability of the nitrile group to coordinate to the gold species. On the
contrary, the addition of 1 equiv of pyridine completely blocked any
reaction and no conversion of 3i was observed after 3 h. Thus, the
presence of pyridine and pyridyl groups deactivates the gold cat-
alytic system.
In order to avoid the unwanted deactivating effect of the cyano-
and pyridyl-moieties on the gold catalyst, the electron-withdraw-
ing alkyne substituent was replaced by a p-benzoate group (3f). The
gold catalysed cyclisation of 1,6-diyne 3f took place with total
regioselectivity, since only the cyclic product 7f was formed (Table
1, entries 9 and 10). Independent on the catalytic system, the
monohydration product 9f was isolated in 31% yield. This indicates
a selective initial gold activation of the methyl substituted alkyne-
moiety, which is supposed to have the highest electron density. The
goldeNHC catalyst afforded stronger activation of the substrate 3f
towards cyclisation and increased the yield of product 7f fourfold
relative to the goldephosphine catalysed reaction from 15% to 61%
(Table 1, entries 9 and 10). No cyclisation reaction was observed
when the monohydrated compound 9f was treated under standard
conditions with either AuCl(PEt3) or AuCl(IMes) in separate
experiments.
As expected, the opposite effect was observed by cyclisation of
a diyne with an electron-donating p-anisole substituent (3g), since
the formation of the other cyclic regioisomer 8g was favoured in
the presence of the phosphine gold complex (Table 1, entry 11; 7g/
8g 27:73). This indicates initial gold activation and subsequent
attack of methanol at the anisole substituted triple bond, which is
supposed to have a higher electron density. The goldeNHC catalyst
was inactive towards the electron rich substrate 3g and no re-
action occurred in the presence of AuCl(IMes) and AgSbF6 (Table 1,
entry 12).
H
R1 = Me
E
E
Me
NaH, Br
l
C
TMS
S
M
T
,
A
D
L
3c
(44%): E = CO2Me
E
Me
H
P
d
(
P
P
C
h3
)
2
E
u
I
,
C
l
2
A
r
B
,
r
,
3b
(89%): E = CO2Me
E
E
Me
Ar
3d (78%): E = CO2Me, Ar = p-C6H4CN
3e
(83%): E = CO2Me, Ar = 2-pyridyl
3f
(70%): E = CO2Me, Ar = p-C6H4CO2Et
3g (55%): E = CO2Me, Ar = p-C6H4OMe
Scheme 2. Preparation of malonate connected 1,6-diynes.
2.2. Gold catalysed cyclisation experiments
The present cyclisation reactions were performed in a similar
manner to the previous studies.10 The standard cyclisation experi-
ments were carried out in methanol at room temperature in the
presence of 5 mol % AuCl(PEt3) or AuCl(IMes). The counter ion ex-
change was achieved by the addition of 6 mol % AgSbF6. The 5-exo-
dig cyclisation of unsymmetrically disubstituted 1,6-diynes IV
would give rise to two possible regioisomers, VI and VII, as shown
in Scheme 3. The steric and electronic nature of the alkyne sub-
stituents R1 and R2 would affect the regioselectivity.
H
O
O
Me
R1
R2
H
[L-Au]+
(R2)
X
O
Me
1
R
X
X
OMe
R1(R2)
R2(R1)
VI
H
O
X
R2(R1)
R2
R1
[L-Au]+
L = PR3 or NHC
X = malonate
IV
V
VII
H
Scheme 3. Formation of two possible regioisomers.
Our previous results10 showed that almost complete regiose-
lectivity was obtained from a Me-/phenyl-substituted diyne 3h
(Table 1, entries 13 and 14), while an approximately 2:1 ratio was
formed from the Me-/Et-diyne 3j in the presence of AuCl(PEt3)
(Table 1, entry 21). The presently studied Me-/t-Bu-diyne 3a would
potentially afford an improved regioselectivity as an initial activa-
tion of the less sterical hindered triple bond was expected. How-
ever, the cyclisation of 3a failed, indicating that the bulky t-Bu-
substituent prevents the cyclisation reaction (Table 1, entries 1 and
2). Thus, only the monohydration product 9a was formed in 79%
and 95% yield by applying the goldephosphine or the goldeNHC
catalyst, respectively. Such monohydration products were also
identified in our previous studies.10

C. Sperger et al. / Tetrahedron 66 (2010) 7749e7754
7751
Table 1
Gold catalysed cyclisations of 1,6-diynesa
Me
O
H
O
H
5 mol% AuCl(L)
6 mol% AgSbF6
MeOH, rt
O
E
E
Me
R
E
E
Me
R
E
E
R
E
E
+
+
Me
R
3a g
-
7a g
-
8a g
-
9a g
-
( E = COOMe)
6a b
-
10a-b
11a-b
12a-b
( E = COOtBu)
Entry
Substrate
R
(L)
T [h]
Temp.
Yieldb [%]
Ratioc
7aeg
8aeg
9aeg
7:8
10aeb
11aeb
12aeb
10:11
1
2
3
4
5
6
7
8
3a
3a
3c
3c
3d
3d
3e
3e
3f
t-Bu
t-Bu
TMS
TMS
p-C6H4CN
p-C6H4CN
2-pyridyl
2-pyridyl
p-C6H4CO2Et
p-C6H4CO2Et
p-C6H4OMe
p-C6H4OMe
C6H5
C6H5
Me
Me
Me
Me
Et
Et
Et
PEt3
22
6.5
7.5
2.5
rt
rt
rt
d
d
d
d
d
d
d
d
95
79
d
d
d
d
d
d
d
d
IMes
PEt3
IMes
PEt3
IMes
PEt3
IMes
PEt3
IMes
PEt3
IMes
PEt3
IMes
PEt3
IMes
PEt3
IMes
PEt3
IMes
PEt3
IMes
24d
e
0
ꢁC to rt
22
rt to 50 ꢁ
rt to 50 ꢁ
rt to 50 ꢁ
C
C
C
No reaction
No reaction
No reaction
No reaction
d
15
15
15
23
24
22
22
3
3
20
6
3
3
rt to 50 ꢁC
9
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
15
61
31
31
d
10
11
12
13
14
15
16
17
18
19
20
21
22
3f
d
3g
3g
3hf
3hf
6b
6b
3if
3if
6a
6a
3jf
3jf
57
27:73
d
No reaction
49
56
d
d
d
d
d
d
d
d
22
d
95:5
97:3
d
54
72
60
60
d
d
d
d
d
d
d
6
22
5
53
42
60
83
62:38
58:42
69:31
48:52
Et
3
a
Reactions were run at 250 mM in MeOH at room temperature with 5 mol % AuCl(L) and 6 mol % AgSbF6.
Isolated yield.
Ratio of isolated cyclic products.
Together with 27% of desilylated product 3b.
Not isolated.
b
c
d
e
f
See Ref. 10.
7j, respectively. In contrast, the more bulky goldeNHC catalyst
afforded an approximately 1:1 mixture. The observed regiose-
lectivity obtained with AuCl(PEt3) is still remarkable, since the
sterical differences between a methyl and an ethyl group is small
(Table 1, entries 19 and 21).
tBu
t Bu
SbF6
P Au NCMe
13
Scheme 4. Acetonitrile coordinated gold complex.
3. Conclusion
As both alkyne groups of diyne 3g have sufficient reactivity to
Further investigations on our recently discovered gold catalysed
cyclisation reaction of 1,6-diynes are reported. By varying the steric
and electronic nature of the alkyne substituents, some features of the
new reaction have been identified. An electron-withdrawing p-ben-
zoate diyne substituent (3f) afforded cyclisation with 100% regiose-
lectivity (7f/8f 100:0) while an electron-donating p-anisole diyne
substituent (3g) gave the opposite regioselectivity (7g/8g 27:73).
Ketone hydration products were only formed from diynes with one
bulky (3a, 3c, 3j) or one electron-withdrawing (3f) substituent. Some
limitationsof the reactionwere observed, as the presence ofa bulky t-
Bu-substituent (3a) prevented the cyclisation reaction. Pyridine and
pyridyl groups (3e) as well as the p-cyanophenyl-substituent (3d)
totally deactivated the gold catalytic system, while TMSealkyne
substrates (3c) underwent desilylation.
be activated by the gold catalyst and further involved in reactions,
cyclisation was preferred. A single monohydration did not take
place and no ketone hydration product 9g was observed. Thus,
ketone products were only formed from diynes with one bulky
(3a, 3c, 3j) or one electron-withdrawing (3f) substituent.
To study the potential influence of the malonate ester moiety
on both, reactivity and regioselectivity, gold catalysed cyclisation
reactions of the di-t-Bu malonates 6a and 6b were carried out.
The reaction of the symmetrically substituted di-t-Bu malonate 6b
provided comparable yields of the cyclopentylidene derivative
10b compared to previous reactions10 of the dimethyl malonate 3i
(Table 1, entries 15e18). The unsymmetrically substituted di-t-Bu
malonate 6a afforded lower yields than the analogous methyl
malonate 3j, indicating some lower reactivity of the sterically
hindered t-Bu-malonate 6a (Table 1, entries 19e22). However, the
regioselectivity seemed to be controlled by the applied gold cat-
alyst, since no explicit changes in the regioselectivity were ob-
served for the sterically demanding substrate 6a compared to the
respective dimethyl malonate substrate 3j. In both cases better
regiocontrol was observed with the goldephosphine complex,
favouring the formation of cyclopentylidene derivatives 10a and
4. Experimental
4.1. General
[AuCl(IMes)]13 was prepared according to literature. All re-
actions were monitored by GC and thin-layer chromatography

7752
C. Sperger et al. / Tetrahedron 66 (2010) 7749e7754
(TLC) using E. Merck silica gel 60 F254 (0.25-mm thickness). Flash
chromatography was carried out using Merck silica gel 60
(0.040e0.063 mm). 1H and 13C NMR spectra were recorded using
a Bruker Avance DPX 300 or 400 MHz spectrometer. Chemical
(Na2SO4) and concentrated in vacuo. After column chromatography
(6% EtOAc/n-pentane) 3a was obtained as a white solid (197 mg,
68%). Mp 53e55 ꢁC; Rf (6% EtOAc/n-pentane) 0.24; nmax (neat) 2966,
1733,1434 cmꢀ1
;
dH (300 MHz, CDCl3) 3.74 (6H, s, 2ꢂOMe), 2.89 (4H,
shifts are reported in parts per million (
d) downfield from tetra-
m, 2ꢂCH2), 1.75 (3H, t, J 2.6 Hz, CH3), 1.17 (9H, s, t-Bu); dC (100 MHz,
CDCl3) 169.7 (2ꢂCO), 92.3 (Calkyne), 78.8 (Calkyne), 73.2 (Calkyne), 72.7
(Calkyne), 57.4 (C(CO2Me)2), 52.7 (2ꢂOMe), 31.1 (C(CH3)3), 27.3 (C
(CH3)3), 22.9 (2ꢂCH2), 3.5 (CH3); m/z (ESI) 279 (MHþ); HRMS (ESI):
MNaþ, found 301.1410. C16H22NaO4 requires 301.1410.
methylsilane (TMS) as internal standard. Coupling constants (J) are
reported in hertz (Hz). The attributions of the chemical shifts were
determined by means of COSY, HMQC and NOESY experiments.
High resolution mass spectra (HRMS) were determined with an
Agilent 6520 QTOF MS instrument equipped with a dual electro-
spray ion source. IR spectra were obtained with a Nicolet 20SXC FT-
IR spectrometer by using a Smart Endurance reflexion cell.
4.1.4. 2-(But-2-ynyl)-2-(prop-2-ynyl)malonate (3b). The title com-
pound 3b was prepared from 2 (1.21 g, 6.57 mmol), NaH (174 mg,
7.25 mmol) in THF (35 mL) and 3-bromo-1-propyne (1.09 g,
7.33 mmol, 80% in toluene) as described above for 3a. Purification
by column chromatography (9% EtOAc/n-pentane) yielded 3b
(1.30 g, 89%) as a white solid. Mp 65e66 ꢁC (lit.17 63e64 ꢁC).
4.1.1. 1-Bromo-4,4-dimethylpent-2-yne. To
a solution of 3,3-di-
methyl-1-butyne (1.07 g, 13.0 mmol) in dry diethyl ether (13 mL),
n-BuLi (7.7 mL, 12.4 mmol, 1.6 M in hexane) was added dropwise
over 15 min at ꢀ78 ꢁC. The reaction mixture was kept at ꢀ78 ꢁC for
15 min. The reaction was heated to ꢀ45 ꢁC and stirring was con-
tinued for additional 45 min. After cooling to ꢀ78 ꢁC, para-
formaldehyde (469 mg, 15.6 mmol) was added as a solid. The
cooling bath was removed and the mixture was stirred at room
temperature for 3 h. Work-up was performed by the addition of
a ammonium chloride solution (25 mL, satd aq) and subsequent
extraction with EtOAc (3ꢂ25 mL). The combined organic layers
were washed with brine (25 mL), dried (Na2SO4) and the solvent
was removed under reduced pressure. Distillation afforded 4,4-
dimethylpent-2-yn-1-ol (974 mg, 67%) as a colourless liquid (bp
51e52 ꢁC/8 mbar). The obtained 1H NMR spectrum was in accor-
dance with the literature.14 To a solution of the alcohol (203 mg,
1.81 mmol) in dry ether (1.25 mL) was added pyridine (12.5 mL) at
4.1.5. Dimethyl
malonate (3c). To an ice cold solution of i-Pr2NH (142 mg, 198
1.41 mmol) in THF (4.5 mL) was added n-BuLi (879 L, 1.41 mmol,
(2-but-2-ynyl)-2-(3-trimethylsilanyl-prop-2-ynyl)
mL,
m
1.6 M in hexane). After 30 min, the reaction mixture was cooled to
ꢀ78 ꢁC and a solution of 3b (252 mg, 1.13 mmol) was added. The
orange solution was stirred for 1 h at ꢀ78 ꢁC and TMSCl (183 mg,
132 mL, 1.69 mmol,) was added. After stirring for additional 4 h, H2O
(20 mL) was added and the aqueous layer was extracted with
diethyl ether (3ꢂ40 mL). The combined organic layers were dried
(Na2SO4) and the solvent was removed under reduced pressure.
The residue was purified by column chromatography (4.5% EtOAc/
n-pentane to 6% EtOAc/n-pentane) to provide 3c (147 mg, 44%) as
a colourless oil. The 1H NMR data were in accordance with the
literature.18
ꢀ30 ꢁC followed by the addition of PBr3 (60
mL, 168 mg, 0.62 mmol)
over 15 min. The solution was slowly heated to room temperature
over 3 h and finally refluxed for 1 h. The reaction mixture was
added dropwise to brine (10 mL) at 0 ꢁC and the aqueous layer was
extracted with diethyl ether (3ꢂ10 mL). The combined organic
layers were washed with brine (10 mL), dried (Na2SO4) and evap-
orated to dryness to yield 1-bromo-4,4-dimethyl-2-pentyne as
a colourless liquid (317 mg, 80%). The product was pure according
to 1H NMR spectroscopy and was used in the next step without
further purification. dH (300 MHz, CDCl3) 3.93 (2H, s, CH2), 1.22 (9H,
s, C(CH3)3).
4.1.6. Dimethyl
2-(but-2-ynyl)-2-(3-(4-cyanophenyl)prop-2-ynyl)
malonate (3d). CuI (17 mg, 0.090 mmol), Pd(PPh3)2Cl2 (32 mg,
0.045 mmol) and 4-bromobenzonitrile (213 mg, 1.17 mmol) were
dissolved in a mixture of THF (1.25 mL) and i-Pr2NH (2.5 mL). After
stirring for 15 min, 3b (200 mg, 0.90 mmol) in THF (1.25 mL) was
added and the reaction mixture was stirred for additional 4 h at
room temperature. The mixture was diluted with EtOAc (50 mL),
filtered and the solvent was removed under reduced pressure.
Purification by column chromatography (14% EtOAc/n-pentane)
yielded 3d (225 mg, 78%) as an orange solid. Mp 92e93 ꢁC; Rf (50%
EtOAc/n-pentane) 0.55; nmax (neat) 2228, 1736, 1604 cmꢀ1
; dH
4.1.2. Dimethyl 2-(but-2-ynyl)malonate (2). To an ice cooled sus-
pension of NaH (407 mg, 17.0 mmol) in THF (35 mL), dimethyl
malonate 19 (4.53 g, 34.3 mmol) was added dropwise over a period
of 20 min. The mixture was stirred at 0 ꢁC for 20 min and 1-bromo-
2-butyne (1.47 g, 11.1 mmol) in THF (2 mL) was added dropwise
over a period of 5 min. After removal of the ice bath, the mixture
was stirred at room temperature for an additional 3 h. Water
(50 mL) was added, the phases were separated and the aqueous
layer was extracted with diethyl ether (3ꢂ50 mL). The combined
organic layers were washed with brine (50 mL), dried (Na2SO4) and
the solvent was removed under reduced pressure. The crude
product was purified by column chromatography (6% EtOAc/n-
pentane) to yield 2 as a colourless oil (1.30 g, 63%). 1H NMR spec-
trum was in accordance with the literature.15
(300 MHz, CDCl3) 7.57 (2H, d, J 8.7 Hz, Harom.), 7.44 (2H, d, J 8.7 Hz,
Harom.), 3.78 (6H, s, 2ꢂOMe), 3.22 (2H, s, CH2), 2.96 (2H, q, J 2.6 Hz,
CH2), 1.77 (3H, t, J 2.6 Hz, CH3); dC (100 MHz, CDCl3) 169.3 (2ꢂCO),
132.2 (Carom.), 131.9 (2ꢂCHarom.), 128.0 (2ꢂCHarom.), 118.4 (CN), 111.4
(Carom.), 89.2 (Calkyne), 82.2 (Calkyne), 79.5 (Calkyne), 72.7 (Calkyne), 56.9
(C(CO2Me)2), 53.1 (2ꢂOMe), 23.7 (CH2), 23.3 (CH2), 3.5 (CH3); m/z
(ESI) 324 (MHþ); HRMS (ESI): MHþ, found 324.1231. C19H18NO4
requires 324.1230.
4.1.7. Dimethyl 2-(but-2-ynyl)-2-(3-(pyridin-2-yl)prop-2-ynyl)mal-
onate (3e). The title compound 3e was prepared from 3b (300 mg,
1.35 mmol) and 2-bromopyridine (277 mg, 1.75 mmol), as de-
scribed above for 3d. Purification by column chromatography (50%
EtOAc/n-pentane) yielded 3e (337 mg, 83%) as a dark orange oil. Rf
4.1.3. Dimethyl 2-(but-2-ynyl)-2-(4,4-dimethyl-pent-2-ynyl)malo-
nate (3a)16. Malonate 2 (195 mg,1.06 mmol) was added dropwise to
an ice cooled suspension of NaH (28.1 mg, 1.17 mmol) in THF (5 mL)
followed by the addition of 1-bromo-4,4-dimethylpent-2-yne
(195 mg,1.11 mmol). The ice bath was removed, and the mixturewas
stirred at room temperature for 4 h. Water (10 mL) was added, and
the aqueous layer was extracted with diethyl ether (3ꢂ20 mL). The
combined organic layers were washed with brine (20 mL), dried
(50% EtOAc/n-pentane) 0.38; nmax (neat) 1736, 1581, 1464 cmꢀ1
; dH
(300 MHz, CDCl3) 8.54 (1H, ddd, J 4.9,1.7, 1.0 Hz, Hpyr.), 7.61 (1H, td, J
7.7, 1.7 Hz, Hpyr.), 7.35 (1H, dt, J 7.7, 1.0 Hz, Hpyr.), 7.20 (1H, ddd, J 7.7,
4.9,1.0 Hz, Hpyr), 3.78 (6H, s, 2ꢂOMe), 3.24 (2H, s, CH2), 3.00 (2H, q, J
2.6 Hz, CH2), 1.76 (3H, t, J 2.6 Hz, CH3); dC (100 MHz, CDCl3) 169.3
(2ꢂCO), 149.8 (CHpyr.), 143.1 (Cpyr.), 135.9 (CHpyr.), 127.2 (CHpyr.),
122.6 (CHpyr), 84.5 (Calkyne), 83.1 (Calkyne), 79.4 (Calkyne), 72.8 (Cal-
kyne), 56.9 (C(CO2Me)2), 53.0 (2ꢂOMe), 23.4 (CH2), 23.2 (CH2), 3.4

C. Sperger et al. / Tetrahedron 66 (2010) 7749e7754
7753
(CH3); m/z (ESI) 322 (MNaþ), 300 (MHþ); HRMS (ESI): MHþ, found
300.1237. C17H18NO4 requires 300.1230.
by column chromatography (6.5% EtOAc/n-hexane) to yield 6a
(269 mg, 75%) as a colourless solid. Mp 66 ꢁC; Rf (6.5% EtOAc/n-
hexane) 0.30; nmax (neat) 2976, 2932, 1729 cmꢀ1
; dH (300 MHz,
4.1.8. Dimethyl
2-(but-2-ynyl)-2-(3-(4-(ethoxycarbonyl)-phenyl)
CDCl3) 2.76e2.83 (4H, m, CH2), 2.12 (2H, qt, J 7.5, 2.4 Hz, CH2CH3),
1.74 (3H, t, J 2.6 Hz, CH3), 1.45 (18H, s, t-Bu), 1.07 (3H, t, J 7.5 Hz,
CH2CH3); dC (100 MHz, CDCl3) 168.4 (2ꢂCO), 84.5 (Calkyne), 81.4
(2ꢂC(CH3)3), 78.3 (Calkyne), 74.0 (Calkyne), 73.8 (Calkyne), 57.7 (C(CO2t-
Bu)2), 27.7 (2ꢂC(CH3)3), 22.8 (CH2), 22.6 (CH2), 14.0 (CH2CH3), 12.3
(CH2CH3), 3.6 (CH3); HRMS (ESI): MNaþ, found 357.2036.
C20H30NaO4 requires 357.2036.
prop-2-ynyl) malonate (3f). The title compound 3f was prepared
from 3b (300 mg, 1.35 mmol) and ethyl 4-bromobenzoate (401 mg,
1.75 mmol) as described above for 3d, except that i-Pr2NH was
replaced by NEt3 (3.7 mL). The crude product was purified by col-
umn chromatography (20% EtOAc/n-pentane) to give the desired
product 3f (349 mg, 70%) as an orange solid. Mp 90e91 ꢁC; Rf (20%
EtOAc/n-pentane) 0.35; nmax (neat) 1735, 1716, 1607 cmꢀ1
; dH
(400 MHz, CDCl3) 7.95 (2H, d, J 8.2 Hz, Harom), 7.41 (2H, d, J 8.2 Hz,
Harom.), 4.37 (2H, q, J 7.2 Hz, CH2CH3), 3.78 (6H, s, 2ꢂOMe), 3.21 (2H,
s, CH2), 2.98 (2H, q, J 2.5 Hz, CH2), 1.77 (3H, t, J 2.5 Hz, CH3), 1.39 (3H,
t, J 7.2 Hz, CH2CH3); dC (100 MHz, CDCl3) 169.4 (2ꢂCO), 166.0 (CO),
131.5 (2ꢂCHarom.), 129.7 (Carom.), 129.3 (2ꢂCHarom.), 127.6 (CHarom.),
87.3 (Calkyne), 83.0 (Calkyne), 79.3 (Calkyne), 72.8 (Calkyne), 61.0
(OCH2CH3), 57.0 (C(CO2Me)2), 53.0 (2ꢂOMe), 23.7 (CH2), 23.2 (CH2),
14.2 (OCH2CH3), 3.5 (CH3); m/z (ESI) 393 (MNaþ), 371 (MHþ); HRMS
(ESI): MHþ, found 371.1491. C21H23O6 requires 371.1489.
4.1.12. Di-tert-butyl 2,2-di(but-2-ynyl)malonate (6b). To an ice cold
suspension of NaH (48.8 mg, 2.03 mmol) in dry THF (4.5 mL) was
subsequently added di-tert-butylmalonate (200 mg, 207
mL,
0.92 mmol) and 1-bromo-2-butyne (271 mg, 178 L, 2.03 mmol) in
m
THF (4.5 mL). After the cooling bath was removed the reaction
mixture was stirred for 3 h at room temperature. H2O (25 mL) was
added and the aqueous layer was extracted with EtOAc (3ꢂ10 mL).
The combined organic layers were dried (Na2SO4) and the solvent
was removed under reduced pressure. The residue was purified by
column chromatography (9% EtOAc/n-hexane) to yield 6b (252 mg,
85%) as a colourless solid. Mp 82 ꢁC; Rf (20% EtOAc/n-hexane) 0.61;
4.1.9. Dimethyl 2-(but-2-ynyl)-2- (3-(4-methoxyphenyl)prop-2-ynyl)
malonate (3g). The title compound 3g was prepared from 3b
(250 mg, 1.13 mmol) and 1-bromo-4-methoxybenzene (274 mg,
1.46 mmol) as described above for 3d. In this reaction DMF (3 mL)
and NEt3 (3 mL) were used as solvent and co-solvent, respectively,
and the reaction mixture was stirred at 80 ꢁC for 17 h. After puri-
fication by column chromatography (14% EtOAc/n-pentane) 3g
(203 mg, 55%) was obtained as a red-orange oil. Rf (20% EtOAc/n-
nmax (neat) 2980, 1750, 1722 cmꢀ1
; dH (300 MHz, CDCl3) 2.78 (4H, q,
J 2.4 Hz, CH2), 1.73 (6H, t, J 2.4 Hz, CH3), 1.45 (18H, s, t-Bu); dC
(100 MHz, CDCl3) 168.5 (2ꢂCO), 81.6 (2ꢂC(CH3)3), 78.4 (2ꢂCalkyne),
73.8 (2ꢂCalkyne), 57.8 (C(CO2t-Bu)2), 27.8 (2ꢂC(CH3)3), 22.7 (CH2),
3.44 (CH3); HRMS (ESI): MNaþ, found 343.1876. C19H28NaO4 re-
quires 343.1880.
hexane) 0.27; nmax (neat) 2954, 1737, 1606 cmꢀ1
;
dH (400 MHz,
4.2. General procedure for cyclisation reactions
CDCl3) 7.29 (2H, d, J 8.8 Hz, Harom.), 6.79 (2H, d, J 8.8 Hz, Harom.), 3.78
(3H, s, OMe), 3.76 (6H, s, 2ꢂCO2Me), 3.16 (2H, s, CH2), 2.98 (2H, q, J
2.6 Hz, CH2), 1.76 (3H, t, J 2.6 Hz, CH3); dC (100 MHz, CDCl3) 169.6
(2ꢂCO), 159.3 (Carom.), 133.0 (2ꢂCHarom.), 115.2 (Carom.), 113.8
(2ꢂCHarom.), 83.4 (Calkyne), 82.4 (Calkyne), 79.1 (Calkyne), 73.0 (Calkyne),
57.2 (C(CO2Me)2), 55.2 (OMe), 52.9 (2ꢂCO2CH3), 23.6 (CH2), 23.1
(CH2), 3.5 (CH3); HRMS (ESI): MHþ, found 329.1388. C19H21O5 re-
quires 329.1384.
In a typical experiment AuCl(L) (5 mol %), AgX (6 mol %) and the
1,6-diyne substrate (50 mg) were suspended in methanol
(c¼250 mM) and stirred at room temperature. The reaction was
carefully monitored by GC, and work-up was performed when full
conversion was achieved or after 24 h. The reaction mixture was
added dropwise to HCl (5 mL, 1 M) and the aqueous layer was
extracted with EtOAc (3ꢂ20 mL). The combined organic layers
were washed with brine (15 mL), dried (Na2SO4) and concentrated
in vacuo. The crude mixture was purified by column
chromatography.
4.1.10. Di-tert-butyl 2-(pent-2-ynyl)malonate (5). To an ice cold
suspension of NaH (147 mg, 6.12 mmol) in THF (10 mL) was added
di-tert-butylmalonate (1.32 g, 1.37 mL, 6.12 mmol). After 1 h 1-
bromo-2-pentyne (300 mg, 209
mL, 2.04 mmol) in THF (2 mL) was
4.2.1. Dimethyl
2-(4,4-dimethylpent-2-ynyl)-2-(3-oxobutyl)malo-
added. The cooling bath was removed and the resulting suspension
was stirred for 23 h at room temperature. After the addition of H2O
(40 mL), the aqueous layer was extracted with EtOAc (3ꢂ50 mL).
The combined organic layers were washed with brine (50 mL),
dried (Na2SO4) and evaporated to dryness. The residue was purified
by column chromatography (50% EtOAc/n-hexane) and subsequent
kugelrohr distillation (0.3 mbar; 65 ꢁC) to yield 5 (376 mg, 65%) as
a colourless oil. Rf (20% EtOAc/n-hexane) 0.55; nmax (neat) 2978,
nate (9a). The reaction of 3a was performed as described in the
general procedure above with AuCl(PEt3) and AgSbF6 for 22 h. Pu-
rification (14% EtOAc/n-heptane) yielded 9a (95%) as a colourless
oil. Rf (50% EtOAc/n-pentane) 0.45; nmax (neat) 2967, 1733,
1436 cmꢀ1
; dH (400 MHz, CDCl3) 3.69 (6H, s, OMe), 2.71 (2H, s, CH2),
2.46 (2H, t, J 7.1 Hz, CH2), 2.26 (2H, t, J 7.1 Hz, CH2), 2.12 (3H, s, CH3),
1.13 (9H, s, t-Bu); dC (100 MHz, CDCl3) 207.1 (CO), 170.6 (2ꢂCOOMe),
92.6 (Calkyne), 72.5 (Calkyne), 56.6 (C(CO2R)2), 52.5 (2ꢂOMe), 38.6
(CH2), 31.0 (C(CH3)3), 29.7 (CH3), 27.3 (C(CH3)3), 26.5 (CH2), 24.0
(CH2); m/z (ESI) 319 (MNaþ), 297 (MHþ); HRMS (ESI): MHþ, found
297.1696. C16H25O5 requires 297.1697.
1727, 1136 cmꢀ1
; dH (300 MHz, CDCl3) 3.30 (1H, t, J 7.8 Hz, CH), 2.62
(2H, d, J 7.8 Hz, CH2), 2.12 (2H, q, J 7.5 Hz, CH2CH3), 1.46 (18H, s, t-
Bu), 1.08 (3H, t, J 7.5 Hz, CH3); dC (100 MHz, CDCl3) 167.6 (2ꢂCO),
83.4 (2ꢂC(CH3)3), 81.6 (Calkyne), 75.3 (Calkyne), 53.5 (CH), 27.8 (2ꢂC
(CH3)3), 22.7 (CH2), 18.6 (CH2), 14.0 (CH2CH3), 12.3 (CH2CH3); HRMS
(ESI): MNaþ, found 305.1723. C16H26NaO4 requires 305.1727.
4.2.2. Dimethyl 2-(but-2-ynyl)-2-(prop-2-ynyl)malonate (3b) and
dimethyl 2-(but-2-ynyl)-2-(2-oxopropyl)malonate (9c). The reaction
was performed according to the general procedure above from 3c
with AuCl(PEt3) and AgSbF6 for 7.5 h. Column chromatography (20%
EtOAc/n-hexane) provided 3b (27%) and 9c (24%) both as colourless
oils. The 1H NMR spectra of 3b are reported previously4 and the 1H
NMR spectra of 9c were in accordance with the literature.10
4.1.11. Di-tert-butyl 2-(but-2-ynyl)-2-(pent-2-ynyl)malonate (6a).
To an ice cold suspension of NaH (30.4 mg, 1.27 mmol) in THF
(7 mL) was added 5 (300 mg, 1.06 mmol) in THF (2 mL). After
10 min 1-bromo-2-butyne (155.4 mg,102 mL,1.17 mmol) was added
and stirring was continued for 4 h. After the addition of H2O
(10 mL) the aqueous layer was extracted with EtOAc (3ꢂ25 mL).
The combined organic layers were dried (Na2SO4) and the solvent
was evaporated under reduced pressure. The residue was purified
4.2.3. (Z)-Dimethyl 3-acetyl-4-(1-(4-(ethoxycarbonyl)-phenyl)ethyl-
idene)cyclopentane-1,1-dicarboxylate (7f) and dimethyl 2-(3-(4-
(ethoxycarbonyl)phenyl)prop-2-ynyl)-2-(3-oxobutyl)malonate

7754
C. Sperger et al. / Tetrahedron 66 (2010) 7749e7754
(9f). The reaction was performed according to the general pro-
cedure above from 3f with AuCl(IMes) and AgSbF6 for 24 h. Column
chromatography (16% EtOAc/n-hexane) yielded 7f (61%) and 9f
(31%), both as colourless oils. 7f: Rf (50% EtOAc/n-hexane) 0.42; nmax
toluene) provided a mixture of 10a and 11a (53%, 10a/11a¼62:38)
as a colourless oil. Compound 10a: Rf (20% EtOAc/n-pentane) 0.48;
dH (300 MHz, CDCl3) 5.43 (1H, t, J 7.6H, ]CH), 3.59 (1H, dd, J 9.0,
7.6 Hz, (CO)CH), 2.91 (1H, dm, J 15.4 Hz, ]CCHaHb), 2.72 (1H, d, J
15.4 Hz, ]CCHaHb), 2.65 (1H, ddd, J 13.4, 9.0, 1.8 Hz, CHCHaHb), 2.17
(1H, dd, J 13.4, 7.6 Hz, CHCHaHb), 2.15 (3H, s, (CO)CH3), 1.91 (2H, m,
CH2CH3), 1.44 (9H, s, t-Bu), 1.42 (9H, s, t-Bu), 0.92 (3H, t, J 7.6 Hz,
CH3). Compound 11a: Rf (20% EtOAc/n-pentane) 0.48; dH (300 MHz,
CDCl3) 5.52 (1H, q, J 6.9 Hz, ]CH), 3.63 (1H, dd, J 8.8, 7.6 Hz, (CO)
CH), 2.92 (1H, dq, J 15.5, 2.2 Hz, ]CCHaHb), 2.73 (1H, d, J 15.5 Hz,
]CCHaHb), 2.65 (1H, ddd, J 13.3, 8.8, 1.5 Hz, CHCHaHb), 2.50 (2H, q, J
7.3 Hz, CH2CH3), 2.20 (1H, dd, J 13.3, 7.6 Hz, CHCHaHb), 1.54 (3H, dm,
J 6.9 Hz, ]CCH3), 1.45 (9H, s, t-Bu), 1.43 (9H, s, t-Bu), 1.05 (3H, t, J
7.3 Hz, CH2CH3); HRMS (ESI) (mixture): MNaþ, found 375.2145.
C20H32NaO5 requires 375.2142.
(neat) 2955,1733,1712,1606 cmꢀ1
; dH (400 MHz, CDCl3) 7.97 (2H, d,
J 8.5 Hz, Harom.), 7.21 (2H, d, J 8.5 Hz, Harom.), 6.60 (1H, s, ]CH), 4.36
(2H, q, J 7.2 Hz, OCH2CH3), 3.97e4.02 (1H, m, (CO)CH), 3.76 (3H, s,
OMe), 3.75 (3H, s, OMe), 3.29 (1H, dt, J 16.6, 2.5 Hz, ]CCHaHb), 3.13
(1H, d, J 16.6 Hz, ]CCHaHb), 2.80 (1H, dd, J 13.5, 2.0 Hz, CHCHaHb),
2.45 (1H, dd, J 13.5, 6.8 Hz, CHCHaHb), 2.00 (3H, s, (CO)CH3), 1.38
(3H, t, J 7.2 Hz, OCH2CH3); dC (100 MHz, CDCl3) 206.9 (CO), 171.4
(COOMe), 171.1 (COOMe), 166.2 (COOEt), 141.4 (C]CH and Carom.),
129.8 (2ꢂCHarom.), 128.9 (Carom.), 127.8 (2ꢂCHarom.), 125.5 (C]CH),
61.0 (OCH2CH3), 58.2 (C(CO2Me)2), 54.1 ((CO)CH), 53.1 (2ꢂOMe),
43.4 (]CCH2), 37.5 (CHCH2), 27.8 ((CO)CH3), 14.3 (OCH2CH3); HRMS
(ESI): MHþ, found 389.1598. C21H25O7 requires 389.1595. 9f: Rf (50%
EtOAc/n-hexane) 0.35; nmax (neat) 2962, 1715, 1606 cmꢀ1
;
dH
4.2.6. (Z)-Di-tert-butyl
3-acetyl-4-ethylidenecyclopentane-1,1-di-
(400 MHz, CDCl3) 7.95 (2H, d, J 8.6 Hz, Harom.), 7.40 (2H, d, J 8.6 Hz,
Harom.), 4.37 (2H, q, J 7.1 Hz, OCH2CH3), 3.76 (6H, s, 2ꢂOMe), 3.06
(2H, s, alkyne-CH2), 2.55 (2H, t, J 8.1 Hz, (CO)CH2), 2.39 (2H, t, J
8.1 Hz, (CO)CH2CH2), 2.15 (3H, s, (CO)CH3), 1.39 (3H, t, J 7.1 Hz,
OCH2CH3); dC (100 MHz, CDCl3) 206.9 (CO),170.5 (2ꢂCOOMe),166.0
(COOEt), 131.5 (2ꢂCHarom.), 129.8 (Carom.), 129.4 (2ꢂCHarom.), 127.5
(Carom.), 87.0 (Calkyne), 83.3 (Calkyne), 61.1 (OCH2CH3), 56.4 (C
(CO2Me)2), 52.9 (2ꢂOMe), 38.6 (CH2), 29.9 (CH3), 26.7 (CH2), 24.9
(CH2), 14.3 (OCH2CH3); m/z (ESI) 411 (MNaþ), 389 (MHþ); HRMS
(ESI): MHþ, found 389.1603. C21H25O7 requires 389.1595.
carboxylate (10b). The reaction of 6b was performed as described
in the general procedure above with AuCl(IMes) and AgSbF6 for 6 h.
Purification by column chromatography (6% EtOAc/n-pentane)
provided 10b (72%) as a colourless oil. Rf (20% EtOAc/n-pentane)
0.46; nmax (neat) 2978, 1723 cmꢀ1
; dH (300 MHz, CDCl3) 5.55 (1H, q,
J 7.0 Hz, CH), 3.60 (1H, dd, J 8.8, 7.6 Hz, (CO)CH), 2.91 (1H, dq, J 15.5,
2.5, CH2), 2.74 (1H, d, J 15.5 Hz, CH2), 2.65 (1H, ddd, J 13.4, 8.8, 1.6,
CH2), 2.22 (1H, dd, J 13.4, 7.6 Hz, CH2), 2.16 (3H, s, CH3),1.56 (3H, dm,
J 7.0 Hz, CH3), 1.45 (9H, s, t-Bu), 1.43 (9H, s, t-Bu); dC (100 MHz,
CDCl3) 208.1 (CO), 170.4 (COOt-Bu), 170.1 (COOt-Bu), 137.9 (C]CH),
120.5 (C]CH), 81.5 (C(CH3)3), 81.3 (C(CH3)3), 60.2 (C(CO2t-Bu)2),
53.3 ((CO)CH), 41.8 (CH2), 36.3 (CH2), 27.8 (2ꢂC(CH3)3), 27.2 ((CO)
CH3), 14.7 (CH3); m/z (ESI) 361 (MNaþ); HRMS (ESI): MNaþ, found
361.1984. C19H30NaO5 requires 361.1985.
4.2.4. (Z)-Dimethyl
3-acetyl-4-(4-methoxybenzylidene)-cyclo-
pentane-1,1-dicarboxylate (7g) and (Z)-dimethyl 3-ethylidene-4-(4-
methoxyphenyl)cyclopentane-1,1-dicarboxylate (8g). The reaction
was performed according to the general procedure above from 3g
with AuCl(PEt3) and AgSbF6 for 22 h. Column chromatography (14%
EtOAc/n-hexane) yielded a mixture of 7g and 8g (57%, 7g/
8g¼27:73) as a colourless oil. Compound 7g: Rf (50% EtOAc/n-
pentane) 0.35; dH (300 MHz, CDCl3) 7.09 (2H, d, J 8.7 Hz, Harom.),
6.84 (2H, d, J 8.7 Hz, Harom.), 6.51 (1H, s, ]CH), 3.92e3.98 (1H, m,
(CO)CH), 3.79 (3H, s, OMe), 3.76 (3H, s, COOMe), 3.74 (3H, s,
COOMe), 3.26 (1H, dt, J 16.1, 2.5 Hz, ]CCHaHb), 3.09 (1H, d, J 16.1 Hz,
]CCHaHb), 2.80 (1H, ddd, J 13.6, 9.0, 1.3 Hz, CHCHaHb), 2.40 (1H, dd,
J 13.6, 7.2 Hz, CHCHaHb), 2.01 (3H, s, (CO)CH3). 8g: Rf (% EtOAc/n-
pentane) 0.33; dH (300 MHz, CDCl3) 8.00 (2H, d, J 8.9 Hz, Harom.),
6.96 (2H, d, J 8.9 Hz, Harom.), 5.57 (1H, q, J 6.7 Hz, ]CH), 4.52 (1H,
dm, J 8.6 Hz, (CO)CH), 3.88 (3H, s, OMe), 3.76 (3H, s, COOMe), 3.70
(3H, s, COOMe), 3.18 (1H, dq, J 15.5, 2.8 Hz, ]CCHaHb), 3.00e2.89
(2H, m, CHCHaHb and ]CCHaHb), 2.22 (1H, dd, J 13.6, 8.6 Hz,
CHCHaHb), 1.39 (3H, dm, J 6.7 Hz, CH3); HRMS (ESI): MHþ, found
347.1485. C19H23O6 requires 347.1489.
References and notes
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7. Belting, V.; Krause, N. Org. Lett. 2006, 8, 4489.
8. Nieto-Oberhuber, C.; Muñoz, M. B.; López, S.; Jiménez-Núñez, E.; Nevado, C.;
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1677.
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12. Carpita, A.; Mannocci, L.; Rossi, R. Eur. J. Org. Chem. 2005, 1859.
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1677.
14. MacInnes, I.; Walton, J. J. Chem. Soc., Perkin Trans. 2 1987, 1077.
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127, 16410.
4.2.5. (Z)-Di-tert-butyl-3-acetyl-4-propylidenecyclopentane-1,1-di-
carboxylate (10a) and (Z)-di-tert-butyl-3-ethylidene-4-propionylcy-
clopentane-1,1-dicarboxylate (11a). The reaction of 6a was
performed as described in the general procedure above with AuCl
(PEt3) and AgSbF6 for 6 h. Column chromatography (2.5% EtOAc/
18. Louie, J.; Gibby, J. E.; Farnworth, M. V.; Tekavec, T. N. J. Am. Chem. Soc. 2002, 124,
15188.