Gold catalysis: Desymmetrization in the furan-yne reaction

Article abstract of DOI:10.1055/s-0029-1218800

A series of seven symmetric difuryl-diynes were synthesized by a route delivering an anti-configurated product as the major product. The gold-catalyzed conversion of the individual anti- and syn-diastereomers was investigated. The anti-diastereomer in a desymmetrization reaction chemoselectively delivered dihydroindenediols with a furyl and a 2-oxopropyl side chain. The syn-diastereomer was completely converted into oligomeric/polymeric material. Thus, it was not necessary to separate the minor amount of the syn-diastereomers from the product mixtures in order to isolate the dihydroindenediols. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0029-1218800

PAPER
2297
Gold Catalysis: Desymmetrization in the Furan–Yne Reaction
G
old
Catalysis:
D
e
.
symmetrizat
S
ion in the
F
ura
t
n–Yne
e
R
eaction phen K. Hashmi,*a Michael Wölfle,b Filiz Ata,a Wolfgang Frey,b Frank Romingera
a
Organisch-Chemisches Institut, Ruprecht-Karls Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
Fax +49(6221)544205; E-mail: hashmi@hashmi.de
Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany
b
Received 5 May 2010
Dedicated to Prof. Rolf Huisgen on the occasion of his 90th birthday
need an oxidant, such as Dess–Martin periodinane, for
this oxidation, but we found that the substrates 2 readily
and selectively oxidize in air, only the formation of 2a
was dependent on the oxidant Dess–Martin periodinane7
Abstract: A series of seven symmetric difuryl-diynes were synthe-
sized by a route delivering an anti-configurated product as the ma-
jor product. The gold-catalyzed conversion of the individual anti-
and syn-diastereomers was investigated. The anti-diastereomer in a
desymmetrization reaction chemoselectively delivered dihydro- (DMP). Thus the formation of the a-furils 7 from furfurals
indenediols with a furyl and a 2-oxopropyl side chain. The syn-dia-
1 overall is an efficient organocatalyzed dimerization/
stereomer was completely converted into oligomeric/polymeric
autoxidation sequence.
material. Thus, it was not necessary to separate the minor amount of
the syn-diastereomers from the product mixtures in order to isolate
the dihydroindenediols.
Table 1 lists the different substrates 7 prepared in the con-
text of this investigation. The two alkyl derivatives 1c and
1d gave low yields of 7c and 7d; the same is true for 7e
and 7f. Thus, these four substrates were not used for the
next step. The aryl derivatives 7g–k were obtained in
good yields (entries 7–11). Single crystals could be grown
of 7b, 7j, and 7l and these were used for crystal structure
analysis (Figure 1). They all show anti-conformation of
the two carbonyl dipoles. In the case of 7b the crystal
packing causes a slight tilt of the molecule, in 7j and 7l the
molecules are planar.
Key words: alkynes, alcohols, furans, gold, homogeneous cataly-
sis, ketones
The exponential growth of homogeneous gold catalysis in
the last decade1 has led to many new synthetic methods
and an increasing number of applications of these meth-
ods in total synthesis.2
In most examples, two identical functional groups in the
substrates will react in an identical manner, as shown for
many gold-catalyzed reactions and different substrates.3
The substituted furfurals 1 were either commercially
available or conveniently accessible by cross-coupling of
5-bromofuran-2-carbaldehyde (9) using the PEPPSI8 cat-
alyst system (Scheme 2). Good results were obtained for
1j and 1k with arylboronic acids, while using alkylboron-
ic acids, the nonbranched butyl group gave 1c in low yield
(9%) and the branched isopropyl group gave no product
1e. We also tried the Pd-X-Phos9 and Umicore CX3110
catalysts in combination with potassium tert-butoxide as
the base, but the furfurals, in our hands, gave unselective
reactions and the products 1 could not be obtained in pure
form.
Based on the gold-catalyzed furan–yne reaction, which
usually delivers phenols as products,4 we have recently in-
vestigated changes in the reaction pathway initiated by
donors on the alkyne or different lengths of the tether be-
tween the furan and alkyne.5
Here we report the synthesis of symmetrical difuran-diyne
substrates by bidirectional synthesis and their gold-cata-
lyzed conversion with desymmetrization leading to prod-
ucts with only one, rather than the expected two, phenol
groups.
The reaction of the substrates 7 with two equivalents of
propargylmagnesium bromide then provided the bis-
homopropargylic diols 8 (Table 1). In most cases good
yields for the twofold addition could be obtained (entries
1, 2, 7, 9–12); the reaction was unselective only in the case
of the bromoarene 7h (entry 8) and the desired product
could not be isolated. Taking into account that after the
first addition the intermediate monoketone is sterically
quite shielded, the overall yields for the twofold addition
are quite good. The diyne substrates 8 were obtained with
low diastereoselectivity, the major diastereomer probably
originating from a Cram-chelate transition state. The ma-
jor diastereomer was assigned from crystal structure anal-
ysis of the product 8a (Figure 2), clearly showing the
relative configuration of the two stereocenters to be anti.11
The other assignments are based on comparison of the
NMR data with the data of 8a, only in the case of 8i (entry
Recently, we published the organocatalytic conversion of
furfurals 1 into the corresponding furoins 2, reduction to
the 1,2-diol 3, propargylation to substrates 4, and subse-
quent gold-catalyzed transformation to give the bis-phe-
nol derivatives 5.6 In the gold-catalyzed step, exclusively
cyclization to the five-membered ring product 5, but not
the isomeric six-membered-ring product 6, was observed
(Scheme 1).
We have now prepared the corresponding symmetrical
1,2-dicarbonyl compounds 7 from the unsymmetrical fu-
roins 2 by oxidation. Initially we assumed that we would
SYNTHESIS 2010, No. 13, pp 2297–2307
x
x.
x
x
.
2
0
1
0
Advanced online publication: 27.05.2010
DOI: 10.1055/s-0029-1218800; Art ID: C03110SS
© Georg Thieme Verlag Stuttgart · New York

2298
A. S. K. Hashmi et al.
PAPER
R1
R2
R1
R2
R2
O
HO
O
O
R2
R1
R2
R1
a
e
O
R1
O
O
O
O
O
2
7
1
b
f
R1
HO
O
R2
R1
R2
O
HO
R2
R1
R2
O
R1
OH
3
OH
O
8
c
R1
R2
O
O
R2
R1
O
O
O
4
d
OH
OH
R1
R2
R1
R2
O
R2
R1
R2
no:
O
6
O
5
R1
OH
OH
Scheme 1 Known synthesis and conversion of 4 and synthesis of the new substrate type 8. Reagents and conditions: (a) thiazolium or triazo-
lium salt (5 mol%), base; (b) NaBH4, MeOH; (c) HC≡CCH2Br, NaH, DMF; (d) AuCl3 (5 mol%), CH2Cl2; (e) DMP or spontaneous oxidation
in air; (f) HC≡CCH2MgBr (2 equiv), THF.
Figure 1 Solid-state structure of 7b (CCDC 776565), 7i (CCDC 776566), 7j (CCDC 776567), and 7l (CCDC 776568)
9) did a comparison with the spectroscopic data of 8a not product 10 now possesses four different functional
allow safe assignment of the anti/syn-diastereomers.
groups, namely a phenol, a tertiary alcohol, a ketone, and
a furan ring. In these initial examples with pure anti-8 the
phenol-type product 10 was isolated in excellent yields;
full conversion was reached within a few minutes. The
formation of side products could not be detected. Table 2
The substrates 8 now in our hands, we first investigated
the reaction of the individual diastereomers. Reaction of
the anti-diastereomer gave selective conversion deliver-
ing phenols of type 10, a reaction that has a loss of sym-
metry from the substrate to the product (Scheme 3). The
Synthesis 2010, No. 13, 2297–2307 © Thieme Stuttgart · New York

PAPER
Gold Catalysis: Desymmetrization in the Furan–Yne Reaction
2299
Table 1 Synthesis of the 1,2-Dicarbonyl Compounds 7 and Twofold Addition of Propargylmagnesium Bromide To Give 8
Entry
Substrate
Yield (%)
Temp (°C) of
Product 8b
R1
R2
H
H
H
H
H
H
H
H
H
H
H
Me
2
7a
Grignard addition
Yieldb (%)
Ratio anti/syn
1
2
1a
1b
1c
1d
1e
1f
Me
666
54c
79
36
–
–50
–10
–
67
65
–
75:25
54:46
–
d
Et
–
e
3
Bu
–
d
f
4
pentyl
i-Pr
–
–
–
–
e
5
–
–
–
–
–
6
NO2
–
–
–
–
–
7
1g
1h
1i
Ph
–
92g
78
92
63
68
91
–20
–20
–20
–10
–10
–10
62
–
64:36
–
8
4-BrC6H4
3-F3CC6H4
2-MeOC6H4
3-MeOC6H4
Me
–
9
986
82
61
69
59
57:43h
54:46
65:35
67:33
d
10
11
12
1j
–
d
1k
–
d
1l
–
a Isolated yield, unless otherwise stated oxidation is by air and the yield is over 2 steps from 1.
b Isolated yield.
c Oxidation is by DMP, yield over two steps from 1a.
d 1 was directly converted into 7.
e Not converted into 2 as the yield of the Suzuki coupling leading to 1c was too low.
f Not converted into 8 as the yield of 7 was too low.
g O2, yield over two steps from 1g.
h No unambiguous assignment of the diastereomers was possible.
summarizes the results with anti-8a, anti-8b, and anti-8g,
all of which gave yields of more than 90%.
N
N
The syn-diastereomer of the substrate reacts completely
unselective, H NMR of the reaction mixture showed no
detectable intermediates and at the end of the reaction no
Cl Pd Cl
N
1
defined products could be isolated (Scheme 3).
Cl
PEPPSI-IPr (2 mol%)
R-B(OH)2
base
R1
O
O
O
O
O
Br
R
HO
O
O
R2
R1
[Au]
R2
R1
R1
R2
HO
1c R = n-Bu (9%)
1e R = i-Pr (–)
1j R = 2-(MeO)C6H4 (84%)
1k R = 3-(MeO)C6H4 (53%)
9
R2
OH
O
OH
anti-8
10
Scheme 2 PEPPSI-catalyzed Suzuki cross-coupling of 5-bromo-
furan-2-carbaldehyde (9)
R1
O
R2
[Au]
HO
unselective reaction
R2
OH
O
R1
syn-8
Scheme 3 Different selectivity is observed when starting from the
individual diastereomers of 8
The reaction conditions were varied for the reaction of
anti-8a (Table 3). Monitoring the reactions by H NMR
Figure 2 Solid state molecular structure of anti-8a (CCDC 776569)
1
showed that gold(III) chloride in dichloromethane (entry
Synthesis 2010, No. 13, 2297–2307 © Thieme Stuttgart · New York

2300
A. S. K. Hashmi et al.
PAPER
Table 2 Gold-Catalyzed Transformations of anti-8 to the Phenol 10
(5 mol% AuCl3, CH2Cl2)
R2
R1
HO
AuCl3
(5 mol%)
R1
R2
HO
O
O
R2
R1
R1
R2
O
Entry
Substrate
anti-8a
anti-8b
anti-8g
R1 (R2 = H) Time (min) Product Yield (%)
O
OH
anti-8
1
2
3
Me
Bu
Ph
5
10
10
10a
10b
10i
92
95
95
10
OH
[Au]
5-exo-dig cyclization
[Au]
~ H+
1) represents the best conditions. In chloroform (entry 2)
the consumption of the substrate is fast, but unselective
and in acetonitrile (entry 3) the isomerization is much
slower, but still selective. The other gold catalysts like a
pyridine complex4c (entry 4) reacted very slowly or, like
the gold(I) complex (entry 5), they were unselective.
HO
HO
5-exo-dig
cyclization
R2
R2
R1
O
OH
O
R1
O
H
OH
OH
R1
Table 3 Testing Different Catalysts and Solvents for the Room-
Temperature Conversion of Substrate anti-8a into 10a
R1
A
B
R2
R2
Scheme 4 Gold-catalyzed cycloisomerization/desymmetrization of
substrates anti-8
Entry Catalyst
Solvent, time Yield (%)
CH2Cl2, 5 min 92
1
2
3
5 mol% AuCl3
R1
R2
5 mol% AuCl3
5 mol% AuCl3
CDCl3, 5 min unselective
CD3CN, 24 h 90
R2
O
R1
O
O
O
H
O
H
O
Au
O
N
R1
4
5
CDCl3, 24 h
50
R1
Cl
OH
OH
Cl
R2
R2
5 mol%
12
3 mol% (m-Cl)-[Au(PPh3]2BF4 CDCl3, 24 h
unselective
Figure 3 Possible hydrogen bridges in the anti- (left) and the syn-
diastereomers (right) of 8
The reactions of anti-8 probably proceed by a 5-exo-dig-
cycloisomerization of the first furyl-yne to the intermedi-
ate A (Scheme 4), the mechanism of this conversion cor-
responds to the well-known phenol synthesis.4f In the next
step the gold catalyst could activate the remaining triple
bond for another nucleophilic addition, in the anti-diaste-
reomer the formation of the enol ether B is conceivable
(intramolecular competition experiments with furyl and
hydroxy nucleophile have shown that the enol ether for-
mation is faster).13 On the other hand, we cannot exclude
that first water is eliminated (creating a conjugation be-
tween the aryl and the furyl ring) and then re-added to the
alkyne (such gold-catalyzed eliminations have been de-
scribed).14 There is no tendency for the elimination of wa-
ter from the indene derivative 10 under these reaction
conditions. We assume that in anti-8 an intramolecular
hydrogen bridge between one furan ring and a distal hy-
droxy group stabilizes a conformation which places the
other furyl group close to the alkyne and thus facilitates
the first cycloisomerization step (Figure 3, left). In the
corresponding syn-8 such an intramolecular hydrogen
bridge stabilizes a conformation that prevents cyclo-
isomerization (Figure 3, right), then gold-catalyzed elim-
ination/condensation chemistry14 takes place and
oligomeric/polymeric material is formed.
8b a reduced yield was obtained (Table 4, entry 1), which
is caused by separation problems in the workup. Com-
pound 8i gave 10i in excellent yield (entry 2), however,
for 8j–l separation problems again led to slightly reduced
yields (entries 3–5).
Table 4 Gold-Catalyzed Conversion of anti/syn-Mixtures of 8 into
10a
Entry
Substrate anti/syn-8
Yieldb (%)
R1
R2
H
1
2
3
4
5
8b
8i
Et
67
95
36
76
72
3-F3CC6H4
2-MeOC6H4
3-MeOC6H4
Me
H
8j
8k
8l
H
H
Me
a Reaction conditions: CD3CN, r.t., 24 h.
b Based on the portion of anti-8.
Efforts to suppress the competing reaction of the hydroxy
groups by protecting them failed. The sterically crowded
environment did not allow for the successful protection of
8 (Scheme 5).
Finally, we investigated the conversion of mixtures of the
two diastereomers, which proceeded nicely. In the case of
Synthesis 2010, No. 13, 2297–2307 © Thieme Stuttgart · New York

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Gold Catalysis: Desymmetrization in the Furan–Yne Reaction
2301
R1
A. TMSCl, imidazole
B. carbodiimidazole
O
R1
R2
PG-O
O
R2
R1
O
R2
R1
HO
R2
O-PG
PG = protecting group
OH
O
8
11
Scheme 5 The TMS- or carbonate-protection of 8 failed
1,2-Bis(5-methylfuran-2-yl)ethan-1,2-dione (7a)
The gold-catalyzed conversions of the two diastereomers
of the difuran-diynes show how the outcome of the gold-
catalyzed conversion can depend on the relative configu-
ration of stereocenters in the substrate. The products ob-
tained from the major diastereomers demonstrate
desymmetrization, converting the substrate into a product
with four quite different functional groups, a phenolic hy-
droxy group, a tertiary alcohol, a ketone, and one remain-
ing furan ring (the latter, for example, can easily be
degraded to a carboxylate15). This work complements the
recent findings on highly diastereoselective reaction of
monofuran diyne substrates.16
Furoin 2a (1.41 g, 6.43 mmol) was dissolved in CH2Cl2 (60 mL).
After cooling to 0 °C, DMP (3.00 g, 7.07 mmol) was added and the
reaction mixture was stirred for 2 h at r.t. and for 2 h at reflux tem-
perature. After the addition of distilled H2O (20 mL) and Et2O (50
mL), the phases were separated and the organic phase was washed
with H2O (2 × 30 mL) and sat. brine (30 mL). After drying the or-
ganic phase with MgSO4 and filtration, the solvent was removed in
vacuo. Column chromatography on silica (PE–EtOAc, 2:1) afford-
ed 7a (1.09 g, 5.02 mmol, 78%) as a colorless solid.17 Rf (PE–
EtOAc, 4:1) = 0.17.
1H NMR (CDCl3, 300 MHz): d = 2.46 (s, 6 H), 6.26 (dd, 3J = 3.6 Hz,
4J = 0.9 Hz, 2 H), 7.53 (d, 3J = 3.6 Hz, 2 H).
1,2-Bis(5-ethylfuran-2-yl)ethane-1,2-dione (7b)
Obtained from 5-ethylfuran-2-carbaldehyde (1b, 1.00 g, 8.06
mmol), THF (15 mL), triazole catalyst (133 mg, 202 mmol), and
K2CO3 (5.57 g, 4.03 mmol) at 70 °C (2 d). The crude product was
purified by column chromatography (silica gel, PE–Et2O, 10:1) to
give 7b (786 mg, 79%) as an orange oil; mp 106 °C; Rf = 0.15 (PE–
Et2O, 10:1).
Commercially available chemicals were used without further puri-
fication. THF and Et2O were dried prior to use. If not indicated oth-
erwise, all reactions were carried out using Schlenk techniques
under an atmosphere of nitrogen. Melting points were determined
on a Büchi SMP-20 melting point apparatus and are uncorrected.
NMR spectra were recorded at r.t. on Bruker ARX500, ARX300 or
ARX250 spectrometers. Chemical shifts (d, ppm) were referenced
to residual solvent protons. Signal multiplicities are as follows: s
(singlet), br s (broad singlet), d (doublet), t (triplet), q (quartet),
IR (film): 3154, 3139, 3126, 2939, 2878, 1815, 1643, 1500, 1454,
1370 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.31 (t, J = 7.5 Hz, 6 H), 2.79 (q,
J = 7.7 Hz, 4 H), 6.26 (d, J = 3.7 Hz, 2 H), 7.54 (d, J = 3.7 Hz, 2 H).
13C NMR (76 MHz, CDCl3): d = 11.64 (q, 2 C), 21.93 (t, 2 C), 77.21
(s, 2 C), 108.57 (d, 2 C), 126.67 (d, 2 C), 151.15 (s, 2 C), 166.66 (s,
2 C).
quint (quintet), m (multiplet). The multiplicities assigned to the 13
C
NMR data are based on a combination of DEPT 135 and DEPT 90
spectra and are defined as follows: s (quarternary C), d (CH), t
(CH2), q (CH3). MS spectra were recorded on Finnigan MAT 90 or
Varian 711 instruments. IR spectra were recorded on a Bruker Vec-
tor 22 spectrophotometer. The fraction of petroleum ether (PE) used
was that with boiling range 70–90 °C.
MS (EI+, 70 eV): m/z (%) = 246 (21) [M]+, 213 (5), 201 (6), 182 (3),
151 (12), 123 (100).
CCDC 776565–776569 contain the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
HRMS (EI+, 70 eV): m/z [M]+ calcd for C14H14O4: 246.0893; found:
246.0893.
Anal. Calcd for C14H14O4 (246.09): C, 68.28; H, 5.73. Found: C,
68.27; H, 5.78.
Organocatalyzed Furil Addition To Give Furoins 7; General
Procedure
1,2-Bis(5-butylfuran-2-yl)ethane-1,2-dione (7c)
The published procedure was used for this transformation.6
Obtained from 5-butylfuran-2-carbaldehyde (1c, 546 g, 3.59
mmol), EtOH (10 mL), thiazolium salt (28.2 mg, 90.0 mmol), and
Et3N (1.49 g, 10.8 mmol) at 80 °C for 1 d. The crude product was
purified by column chromatography (silica gel, PE–Et2O–CH2Cl2,
12:2:1) to give 7c (200 mg, 36%) as a yellow oil; Rf = 0.35 (PE–
Et2O, 5:1).
2-Hydroxy-1,2-bis(5-methylfuran-2-yl)ethanone (2a)
Obtained from 5-methylfuran-2-carbaldehyde (1a, 10.0 g, 90.8
mmol), Et3N (3.8 mL, 27.3 mmol) and thiazolium catalyst (142 mg,
4.52 mmol, 5 mol%) in abs EtOH (30 mL). The mixture was stirred
under reflux for 3 h and the product was precipitated by addition of
cold H2O and purified by recrystallization (EtOH) to give the prod-
uct (6.85 g, 31.1 mmol, 69%) as a yellow solid. The spectroscopic
data is in accordance with the literature.17
1H NMR (300 MHz, CDCl3): d = 2.24 (d, J = 1.0 Hz, 3 H), 2.38 (s,
3 H), 4.21 (br s, 1 H), 5.65 (s, 1 H), 5.91 (dq, J = 3.1, 1.0 Hz, 1 H),
6.14 (dq, J = 3.6, 0.9 Hz, 1 H), 6.25 (d, J = 3.1 Hz, 1 H), 7.12 (d,
J = 3.6 Hz, 1 H).
IR (film): 3433, 2960, 2928, 2873, 1736, 1499 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.87 (m, 6 H), 1.26 (m, 4 H), 1.64
(m, 4 H), 2.69 (t, J = 7.6 Hz, 4 H), 6.07 (d, J = 3.8 Hz, 2 H), 6.18 (d,
J = 3.6 Hz, 2 H).
13C NMR (76 MHz, CDCl3): d = 13.71 (q, 2 C), 22.27 (t, 2 C), 28.25
(t, 2 C), 29.72 (t, 2 C), 77.20 (s, 2 C), 108.30 (d, 2 C), 109.27 (d, 2
C), 146.17 (s, 2 C), 165.65 (s, 2 C).
MS (EI+, 70 eV): m/z (%) = 302 (4), 204 (4), 139 (13), 91 (100)
[M]+.
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2302
A. S. K. Hashmi et al.
PAPER
HRMS (EI+, 70 eV): m/z [M]+ calcd for C18H22O4: 302.1518; found:
302.1510.
1H NMR (300 MHz, CDCl3): d = 3.90 (s, 6 H), 6.92 (d, J = 3.2 Hz,
2 H), 7.00 (d, J = 7.5 Hz, 2 H), 7.09 (d, J = 3.8 Hz, 2 H), 7.72 (t, J =
7.1 Hz, 2 H), 7.31 (t, J = 7.1 Hz, 2 H), 8.04 (t, J = 7.7 Hz, 2 H).
1,2-Bis(5-phenylfuran-2-yl)ethane-1,2-dione (7g)
13C NMR (76 MHz, CDCl3): d = 55.51 (q, 2 C), 111.19 (d, 2 C),
113.13 (d, 2 C), 117.92 (s, 2 C), 121.00 (d, 2 C), 127.23 (d, 2 C),
127.83 (d, 2 C), 130.92 (d, 2 C), 147.80 (s, 2 C), 157.00 (s, 2 C),
157.53 (s, 2 C), 176.91 (s, 2 C).
MS (EI+, 70 eV): m/z (%) = 402 (27) [M]+, 396 (16), 376 (13), 341
(16), 313 (45), 285 (9), 269 (67), 253 (18), 224 (20), 201 (100), 189
(90).
Obtained from 5-phenylfuran-2-carbaldehyde (1g, 2.00 g, 11.6
mmol), thiazolium salt (182 mg, 581 mmol, 5 mol%), Et3N (391 mg,
3.87 mmol), and EtOH (20 mL) at reflux for 2 h. Stirring was con-
tinued under an atmosphere of O2 at 60 °C for 72 h. Filtration of the
crude product (silica gel) gave 7g (1.83 g, 5.35 mmol, 92%) as a yel-
low solid; mp 189–192 °C; Rf = 0.57 (PE–Et2O, 2:1).
IR (film): 1644, 1469, 1256, 1029, 972, 753, 677 cm–1.
1H NMR (500 MHz, CDCl3): d = 6.88 (d, J = 3.8 Hz, 2 H), 7.40–
7.48 (m, 6 H), 7.75 (d, J = 3.8 Hz, 2 H), 7.86–7.89 (m, 4 H).
HRMS (EI+, 70 eV): m/z [M]+ calcd for C24H18O6: 402.3961; found:
402.1110.
13C NMR (126 MHz, CD2Cl2): d = 108.31 (d, 2 C), 125.62 (d, 4 C),
127.18 (d, 2 C), 128.79 (s, 2 C), 128.99 (d, 4 C), 130.02 (d, 2 C),
148.86 (s, 2 C), 160.66 (s, 2 C), 176.55 (s, 2 C).
MS (ESI+): m/z (%) = 365 (100) [M + Na]+.
HRMS (ESI-EM): m/z [M + Na]+ calcd for C22H14NaO4: 365.0784;
1,2-Bis[5-(3-methoxyphenyl)furan-2-yl]ethane-1,2-dione (7k)
Obtained from 5-(3-methoxyphenyl)furan-2-carbaldehyde (1k,
2.00 g, 9.89 mmol), THF (60 mL), triazolium salt (141 mg, 500
mmol), and K2CO3 (4.19 g 29.7 mmol) at 70 °C for 2 d. Column
chromatography of the crude product (silica gel, PE–Et2O–CH2Cl2,
12:2:1) gave 7k (1.35 g, 68%) as a yellow solid; mp 128–136 °C;
Rf = 0.20 (PE–Et2O–CH2Cl2, 12:2:1).
found: 365.0772.
IR (film): 3440, 3165, 1637, 1603, 1510 cm–1.
Anal. Calcd for C22H14O4 (342.34): C, 77.18; H, 4.12. Found: C,
76.93; H, 4.26.
1H NMR (250 MHz, CDCl3): d = 3.81 (s, 6 H), 6.79 (d, J = 3.8 Hz,
2 H), 6.89 (d, J = 6.5 Hz, 2 H), 7.25–7.39 (m, 6 H), 7.66 (d, J = 3.8
Hz, 2 H).
13C NMR (76 MHz, CDCl3): d = 55.49 (q, 2 C), 108.61 (d, 2 C),
110.59 (d, 2 C), 116.11 (d, 2 C), 118.24 (d, 2 C), 127.18 (d, 2 C),
130.09 (d, 2 C), 148.83 (s, 2 C), 160.05 (s, 2 C), 160.54 (s, 2 C),
176.52 (s, 2 C).
1,2-Bis[5-(4-bromophenyl)furan-2-yl]ethane-1,2-dione (7h)
Obtained from 5-(4-bromophenyl)furan-2-carbaldehyde (1h, 350
mg, 1.40 mmol), Et3N (27.6 mg, 140 mmol), thiazolium catalyst
(23.0 mg, 70 mmol, 5 mol%), and EtOH (10 mL). Column chroma-
tography of the crude product (silica gel, PE–EtOAc, 3:1) gave 7h
(271 mg, 1.09 mmol, 78%) as a yellow oil. Rf = 0.20 (PE–Et2O, 6:1).
The product still contained some starting material which could not
be separated, thus it was not converted in the next step.
MS (ESI+): m/z (%) = 403 (100) [M + H]+.
HRMS (ESI+): m/z [M + H]+ calcd for C24H19O6: 403.4041; found:
403.1176.
1,2-Bis{5-[3-(trifluoromethyl)phenyl]furan-2-yl}ethane-1,2-di-
one (7i)
1,2-Bis(4,5-dimethylfuran-2-yl)ethane-1,2-dione (7l)
Obtained from 5-[3-(trifluoromethyl)phenyl]furan-2-carbaldehyde
(1i, 500 mg, 2.08 mmol), Et3N (63.1 mg, 624 mmol), thiazolium cat-
alyst (32.7 mg, 104 mmol, 5 mol%), and EtOH (10 mL). Column
chromatography of the crude product (silica gel, PE–Et2O, 6:1)
gave 7i (458 mg, 1.91 mmol, 92%) as a yellow solid; mp 177–178
°C; Rf = 0.29 (PE–Et2O, 4:1).
Obtained from 2,5-dimethylfuran-2-carbaldehyde (1l, 2.00 g, 16.1
mmol), THF (20 mL), triazolium salt (133 mg, 810 mmol), and
K2CO3 (6.68 g 48.3 mmol) at 70 °C for 2 d. Column chromatogra-
phy of the crude product (silica gel, PE–Et2O, 10:1) gave 7l (1.80 g,
91%) as an orange solid; mp 135 °C; Rf = 0.10 (PE–Et2O, 10:1).
IR (film): 1633, 1498, 1294, 1163, 1127, 950, 810, 696 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.00 (s, 6 H), 2.35 (s, 6 H), 7.38
(2 H).
13C NMR (76 MHz, CDCl3): d = 9.66 (q, 2 C), 12.25 (q, 2 C), 77.21
(s, 2 C), 118.91 (d, 2 C), 147.27 (s, 2 C), 157.60 (s, 2 C), 176.91 (s,
2 C).
MS (EI+, 70 eV): m/z (%) = 246 (17) [M]+, 201 (3), 182 (2), 151 (8),
123 (100), 111 (11).
HRMS (EI+, 70 eV): m/z [M]+ calcd for C14H14O4: 246.0893; found:
246.0883.
IR (film): 1646, 1504, 1447, 1327, 1271, 1248, 1159, 1110, 1094,
1068, 1028, 974, 796, 770, 689, 650 cm–1.
3
1H NMR (500 MHz, CDCl3): d = 6.97 (d, J = 4.0 Hz, 2 H), 7.60
(dd, 3J = 8.0 Hz, 3J = 7.5 Hz, 2 H), 7.65 (d, 3J = 8.0 Hz, 2 H), 7.78
(d, 3J = 4.0 Hz, 2 H), 8.04 (d, 3J = 7.5 Hz, 2 H), 8.08 (s, 2 H).
13C NMR (125 MHz, CDCl3): d = 109.36 (d, 2 C), 122.31 [d, 2 C (q,
3JC-F = 3.6 Hz)], 124.91 [s, 2 C (q, 1JC-F = 273.8 Hz)], 126.43 [d, 2
C (q, 3JC-F = 3.7 Hz)], 127.05 (d, 2 C), 128.61 (d, 2 C), 129.36 (d, 2
C), 129.65 (d, 2 C), 131.69 [s, 2 C (q, 2JC-F = 32.6 Hz)], 149.20 (s,
2 C), 158.79 (s, 2 C), 176.20 (s, 2 C).
MS (EI+, 70 eV): m/z (%) = 478 (12) [M]+, 239 (100), 183 (23).
PEPPSI-Catalyzed Cross-Coupling for the Synthesis of Substi-
tuted Furfurals 1
5-Butylfuran-2-carbaldehyde (1c)
Anal. Calcd for C24H12F6O4 (478.38): C, 60.26; H, 2.53. Found: C,
60.04; H, 2.42.
5-Bromofuran-2-carbaldehyde (4.81 g, 27.4 mmol), butylboronic
acid (3.34 g, 32.8 mmol), K2CO3 (11.4 g, 82.4 mmol), and PEPPSI
(465 mg, 685 mmol) were dissolved in dioxane (50 mL) and H2O (10
mL). The mixture was stirred overnight at 95 °C, then filtered
through Celite and the solvent was removed in vacuo. Column chro-
matography (silica gel, PE–Et2O, 3:1) gave 1c (546 mg, 9%) as an
orange oil.
1,2-Bis[5-(2-methoxyphenyl)furan-2-yl]ethane-1,2-dione (7j)
Obtained from 5-(2-methoxyphenyl)furan-2-carbaldehyde (1j, 4.08
g, 20.2 mmol), THF (55 mL), triazolium salt (282 mg, 1.01 mmol),
and K2CO3 (13.9 g 101 mmol) at 70 °C for 2 d. Column chromatog-
raphy of the crude product (silica gel, PE–Et2O–CH2Cl2, 10:2:1)
gave 7j (2.55 g, 63%) as a yellow solid; mp 165 °C; Rf = 0.20 (PE–
Et2O–CH2Cl2, 12:2:1).
Rf = 0.46 (PE–Et2O, 3:1).
IR (film): 3797, 3758, 3680, 3051, 2964, 1636, 1602, 1505, 1485,
1447 cm–1.
IR (film): 3122, 2961, 2934, 2874, 1728, 1680, 1581, 1518, 1466,
1433 cm–1.
Synthesis 2010, No. 13, 2297–2307 © Thieme Stuttgart · New York

PAPER
Gold Catalysis: Desymmetrization in the Furan–Yne Reaction
4,5-Bis(5-methylfuran-2-yl)octa-1,7-diyne-4,5-diol (8a)
2303
1H NMR (250 MHz, CDCl3): d = 0.79 (t, J = 9.0 Hz, 2 H), 1.13–
1.28 (m, 2 H), 1.47–1.57 (m, 2 H), 2.56 (t, J = 9.0 Hz, 3 H), 6.11 (d,
J = 3.0 Hz, 1 H), 7.06 (d, J = 3.0 Hz, 1 H), 9.35 (s, 1 H).
13C NMR (76 MHz, CDCl3): d = 13.31 (q), 21.72 (t), 27.71 (t),
29.26 (t), 108.39 (d), 151.42 (s), 167.83 (s), 176.63 (d).
MS (EI+, 70 eV): m/z (%) = 152 (74) [M]+, 123 (17), 109 (100), 81
(29), 67 (3), 53 (14), 38 (9), 26 (9).
HRMS (EI+, 70 eV): m/z [M]+ calcd for C9H12O2: 152.0837; found:
152.0845.
To 7a (200 mg, 917 mmol) at –50 °C was added slowly 1.96 M pro-
pargylmagnesium bromide in Et2O (1.87 mL, 3.67 mmol) in THF
(20 mL). The crude product was purified by column chromatogra-
phy (silica gel, PE–Et2O, 4:1) to provide 8a (184 mg, 616 mmol,
67%) as a yellow solid; ratio of diastereomers anti-8a/syn-8a 75:25.
A second chromatographic separation (silica gel, PE–Et2O, 6:1)
gave pure fractions of both diastereomers. Single crystals of the
anti-diastereomer were characterized by a single crystal structure
analysis; this crystal was then redissolved and a 1H NMR spectrum
was measured in order to confirm the assignment of the structure to
the 1H NMR of the major diastereomer.
5-(2-Methoxyphenyl)furan-2-carbaldehyde (1j)
5-Bromofuran-2-carbaldehyde (4.81 g, 27.4 mmol), 2-methoxyphe-
nylboronic acid (5.00 g, 32.9 mmol), K2CO3 (11.4 g, 82.4 mmol),
and PEPPSI (280 mg, 412 mmol) were dissolved in dioxane (20 mL)
and H2O (4 mL). The mixture was stirred at 95 °C overnight then
filtered through Celite and the solvent was removed in vacuo. Col-
umn chromatography of the crude product (silica gel, PE–Et2O–
CH2Cl2, 10:2:1) gave 1j (4.64 g, 84%) as an orange oil.
anti-8a
Mp 74–76 °C; Rf = 0.26 (PE–Et2O; 4:1).
IR (film): 3514, 3292, 2929, 1732, 1556, 1328, 1194, 1022, 955,
777, 664, 627 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.91 (t, J = 2.6 Hz, 2 H), 2.28 (d,
J = 1.0 Hz, 6 H), 2.75 (dd, J = 17.0, 2.6 Hz, 2 H), 3.05 (br s, 2 H),
3.09 (J = 17.0, 2.6 Hz, 2 H), 5.95 (dq, J = 3.2, 1.0 Hz, 2 H), 6.23 (d,
J = 3.2 Hz, 2 H).
Rf = 0.25 (PE–Et2O–CH2Cl2, 10:2:1).
IR (film): 3075, 2950, 2825, 2750, 1717, 1671, 1602, 1515, 1489,
1433 cm–1.
MS (EI+, 70 eV): m/z (%) = 298 (3) [M]+, 241 (1), 149 (48), 109
1H NMR (300 MHz, CDCl3): d = 3.98 (s, 3 H), 7.01 (d, J = 8.4 Hz,
1 H), 7.08 (t, J = 7.6 Hz, 1 H), 7.15 (d, J = 3.7 Hz, 1 H), 7.34 (d,
J = 3.7 Hz, 1 H), 7.36–7.41 (m, 1 H), 8.07 (d, J = 7.8 Hz, 1 H), 9.66
(s, 1 H).
(100).
HRMS (EI, 70 eV): m/z [M]+ calcd for C18H18O4: 298.1205; found:
298.1202.
13C NMR (76 MHz, CDCl3): d = 55.48 (q), 111.18 (d), 112.57 (d),
120.94 (d), 127.43 (d), 130.65 (d), 150.89 (s), 156.20 (s), 156.82 (s),
177.20 (d).
MS (EI+, 70 eV): m/z (%) = 202 (100) [M]+, 201 (3), 158 (6), 145
(11), 131 (20), 115 (9), 102 (6), 77 (4).
HRMS (EI+, 70 eV): m/z [M]+ calcd for C12H10O3: 202.0630; found:
202.0636.
syn-8b
Rf = 0.21 (PE–Et2O; 4:1).
1H NMR (300 MHz, CDCl3): d = 1.89 (t, J = 2.6 Hz, 2 H), 2.25 (d,
J = 1.0 Hz, 6 H), 2.72 (dd, J = 16.8, 2.6 Hz, 2 H), 3.07 (J = 16.8, 2.6
Hz, 2 H), 3.25 (br s, 2 H), 5.92 (dq, J = 3.2, 1.0 Hz, 2 H), 6.21 (d,
J = 3.2 Hz, 2 H).
13C NMR: (CDCl3, 75.5 MHz): d = 13.69 (q, 2 C), 26.74 (t, 2 C),
71.48 (d, 2 C), 77.28 (s, 2 C), 79.61 (s, 2 C), 106. 54 (d, 2 C), 109.60
(d, 2 C), 151.93 (s, 2 C), 151.95 (s, 2 C).
5-(3-Methoxyphenyl)furan-2-carbaldehyde (1k)
5-Bromfuran-2-carbaldehyde (4.81 g, 27.4 mmol), 3-methoxyphe-
nylboronic acid (5.00 g, 32.9 mmol), K2CO3 (11.4 g, 82.4 mmol),
and PEPPSI (486 mg, 715 mmol) were dissolved in dioxane (20 mL)
and H2O (4 mL). The mixture was heated to 95 °C overnight then
filtered through Celite and the solvent was removed in vacuo. Puri-
fication of the crude product by column chromatography (silica gel,
PE–Et2O–CH2Cl2, 10:2:1) gave 1k (2.92 g, 53%) as an orange oil;
Rf = 0.25 (PE–Et2O–CH2Cl2, 10:2:1).
IR (film): 3075, 2950, 2825, 2750, 1675, 1589, 1569, 1519 cm–1.
1H NMR (250 MHz, CDCl3): d = 3.78 (s, 3 H), 6.75 (d, J = 6.0 Hz,
1 H), 6.86 (d, J = 12.0 Hz, 1 H), 7.23–7.33 (m, 4 H), 9.56 (s, 1 H).
4,5-Bis(5-ethylfuran-2-yl)octa-1,7-diyne-4,5-diol (8b)
To 7b (450 mg, 1.83 mmol) in Et2O (15 mL) at –10 °C was slowly
added 1.09 M propargylmagnesium bromide (6.7 mL, 7.31 mmol);
stirring was continued at r.t. for 4 h. Column chromatography (silica
gel, PE–Et2O, 3:1) gave anti-8b (151 mg, 37%) and syn-8b (132
mg, 28%) as yellow oils.
anti-8b
Rf = 0.38 (PE–Et2O, 3:1).
IR (film): 3529, 3292, 2973, 2940, 2123, 1692, 1556, 1324, 1203,
1094 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.16 (t, J = 7.6 Hz, 6 H), 1.87 (t,
J = 2.4 Hz, 4 H), 2.60 (q, J = 7.7 Hz, 2 H), 2.72 (dd, J = 16.8, 2.7
Hz, 2 H), 3.05 (br s, 2 H), 3.03 (dd, J = 16.8, 2.7 Hz, 2 H), 5.90 (d,
J = 3.2 Hz, 2 H), 6.18 (d, J = 3.2 Hz, 2 H).
13C NMR (76 MHz, CDCl3): d = 55.42 (q), 108.03 (d), 110.34 (d),
115.71 (d), 117.89 (d), 130.05 (d), 177.29 (d), 157.70 (s), 159.30
(s), 160.03 (s).
MS (EI+, 70 eV): m/z (%) = 202 (100) [M]+, 201 (17), 174 (3), 145
(20), 131 (3), 115 (6), 102 (6).
HRMS (EI+, 70 eV): m/z [M]+ calcd for C12H10O3: 202.0630; found:
202.0643.
13C NMR (76 MHz, CDCl3): d = 12.04 (q, 2 C), 21.32 (t, 2 C), 26.61
(t, 2 C), 71.29 (d, 2 C), 77.22 (s, 2 C), 79.48 (s, 2 C), 104.80 (d, 2
C), 109.14 (d, 2 C), 151.72 (s, 2 C), 157.54 (s, 2 C).
MS (EI+, 70 eV): m/z (%) = 326 (3) [M]+, 269 (4), 213 (3), 163 (86),
123 (100).
HRMS (EI+, 70 eV): m/z [M]+ calcd for C20H22O4: 326.1518; found:
326.1523.
Grignard Addition to the Furoins 7 To Give Bis-furyl-diynes 8
General Workup
After addition of sat. aq NH4Cl soln (10 mL), the aqueous layer was
extracted with Et2O (3 × 10 mL). The combined organic layers were
dried (MgSO4) and filtered and the solvent was removed in vacuo.
The conditions of the chromatographic workup are mentioned in the
individual experiments.
syn-8b
Rf = 0.34 (PE–Et2O, 3:1).
1H NMR (300 MHz, CDCl3): d = 1.13 (t, J = 7.4 Hz, 6 H), 1.89 (t,
J = 2.4 Hz, 2 H), 2.52 (q, J = 7.1 Hz, 4 H), 2.74 (dd, J = 16.9, 2.7
Synthesis 2010, No. 13, 2297–2307 © Thieme Stuttgart · New York

2304
A. S. K. Hashmi et al.
PAPER
Hz, 2 H), 2.98 (dd, J = 17.1, 2.8 Hz, 2 H), 3.21 (br s, 2 H), 5.88 (d,
J = 3.0 Hz, 2 H), 6.15 (d, J = 3.0 Hz, 2 H).
13C NMR (76 MHz, CDCl3): d = 12.03 (q, 2 C), 21.93 (d, 2 C),
26.28 (t, 2 C), 71.29 (d, 2 C), 77.21 (s, 2 C), 80.12 (s, 2 C), 104.73
(d, 2 C), 109.33 (d, 2 C), 151.09 (s, 2 c), 157.48 (s, 2 C).
120.21 (d, JC-F = 4 Hz, 2 C/2 C), 123.68/123.83 (d, JC-F = 4 Hz, 2 C/
2 C), 123.85/123.96 (s, JC-F = 272 Hz, 2 C/2 C), 126.35/126.59 (d,
2 C/2 C), 128.81/129.07 (d, 2 C/2 C), 130.72/131.04 (s, 2 C/2 C),
130.81/131.09 (s, JC-F = 33 Hz, 2 C/2 C), 152.25/152.26 (s, 2 C/2
C), 153.39/154.02 (s, 2 C/2 C). * In the diastereomeric mixture the
signals of both diastereomers could not be assigned.
4,5-Bis(5-phenylfuran-2-yl)octa-1,7-diyne-4,5-diol (8g)
To 7g (600 mg, 1.75 mmol) in THF (20 mL) at –20 °C was slowly
added 1.96 M propargylmagnesium bromide in Et2O (1.79 mL, 3.50
mmol). Column chromatography (silica gel, PE–Et2O, 8:1) gave
anti-8g (263 mg, 624 mmol, 36%) as a yellow solid and syn-8g (194
mg, 459 mmol, 26%). The assignment of the diastereomers is based
on the direct comparison with the 1H NMR spectra of the diastere-
omers 8a.
MS (EI+, 70 eV): m/z (%) = 279 (59), 239 (100).
MS (ESI-EM): m/z [M + Na]+ calcd for C30H20F6NaO4: 581.1158,
found 581.1156.
4,5-Bis[5-(2-methoxyphenyl)furan-2-yl]octa-1,7-diyne-4,5-diol
(8j)
To 7j (1.55 g, 6.30 mmol) in Et2O (60 mL) at –10 °C was slowly
added 1.33 M propargylmagnesium bromide in Et2O (18.9 mL, 25.1
mmol); the mixture was stirred at r.t. for 4 h. Column chromatogra-
phy (silica gel, PE–Et2O–CH2Cl2, 12:2:1) provided anti-8j (974 mg,
32%) and syn-8j (887 mg, 29%) as yellow solids.
anti-8g
Mp 170–173 °C; Rf = 0.47 (PE–Et2O, 2:1).
IR (film): 3539, 3269, 1483, 1332, 1086, 1025, 971, 760, 686, 650
cm–1.
anti-8j
Mp 42 °C; Rf = 0.14 (PE–Et2O–CH2Cl2, 12:2:1).
1H NMR (500 MHz, CDCl3): d = 1.94 (t, J = 2.6 Hz, 2 H), 2.96 (dd,
J = 16.8, 2.6 Hz, 2 H), 3.27 (br s, 2 OH), 3.27 (dd, J = 16.8, 2.6 Hz,
2 H), 6.45 (d, J = 3.4 Hz, 2 H), 6.60 (d, J = 3.4 Hz, 2 H), 7.22–7.26
(m, 2 H), 7.32–7.35 (m, 4 H), 7.57–7.59 (m, 4 H).
13C NMR (126 MHz, CD2Cl2): d = 26.74 (t, 2 C), 72.02 (d, 2 C),
77.34 (s, 2 C), 78.99 (s, 2 C), 105.84 (d, 2 C), 110.95 (d, 2 C),
123.70 (d, 4 C), 127.41 (d, 2 C), 128.64 (d, 4 C), 130.54 (s, 2 C),
153.30 (s, 2 C), 153.71 (s, 2 C).
IR (film): 3590, 3452, 3265, 2940, 2837, 1674, 1602, 1489, 1466,
1434 cm–1.
1H NMR (250 MHz, CDCl3): d = 1.76 (t, J = 2.4 Hz, 2 H), 2.74 (dd,
J = 2.5, 16.8 Hz, 2 H), 2.90 (dd, J = 2.5, 16.8 Hz, 2 H), 3.12 (s, 2 H),
3.72 (s, 6 H), 6.29 (d, J = 5.0 Hz, 2 H), 6.54–7.07 (m, 8 H), 7.33 (d,
J = 2.5 Hz, 2 H).
13C NMR (76 MHz, CDCl3): d = 26.83 (t, 2 C), 55.36 (q, 2 C), 71.82
(d, 2 C), 79.76 (s, 2 C), 110.99 (d, 2 C), 111.22 (d, 2 C), 119.62 (d,
2 C), 120.67 (d, 2 C), 126.04 (d, 2 C), 128.11 (d, 2 C), 150.28 (s, 2
C), 151.55 (s, 2 C), 152.37 (s, 2 C), 155.38 (s, 2 C); one s, 2 C not
detected.
MS (EI+, 70 eV): m/z (%) = 422 (2) [M]+, 211 (100), 171 (98), 115
(26).
Anal. Calcd for C28H22O4 (422.47): C, 79.60; H, 5.25. Found: C,
79.39; H, 5.36.
MS (ESI+, 70 eV): m/z (%) = 428 (11) [M]+, 464 (11), 269 (100),
syn-8g
241 (51).
Rf = 0.44 (PE–Et2O, 2:1).
HRMS (ESI+, 70 eV): m/z [M]+ calcd for C30H26O6: 482.1729;
found: 482.1694.
1H NMR (500 MHz, CDCl3): d = 1.97 (t, J = 2.6 Hz, 2 H), 2.93 (dd,
J = 17.0, 2.6 Hz, 2 H), 3.19 (dd, J = 16.8, 2.6 Hz, 2 H), 3.39 (br s, 2
OH), 6.50 (d, J = 3.4 Hz, 2 H), 6.63 (d, J = 3.4 Hz, 2 H), 7.13–7.21
(m, 6 H), 7.44–7.46 (m, 4 H).
syn-8j
Rf = 0.10 (PE–Et2O–CH2Cl2, 12:2:1).
13C NMR (126 MHz, CD2Cl2): d = 26.48 (t, 2 C), 71.85 (d, 2 C),
77.27 (s, 2 C), 79.72 (s, 2 C), 105.65 (d, 2 C), 111.19 (d, 2 C),
123.67 (d, 4 C), 127.31 (d, 2 C), 128.44 (d, 4 C), 130.32 (s, 2 C),
152.53 (s, 2 C), 153.86 (s, 2 C).
1H NMR (250 MHz, CDCl3): d = 1.75 (t, J = 2.5 Hz, 2 H), 2.75 (dd,
J = 2.5, 17.5 Hz, 2 H), 3.95 (dd, J = 2.4, 16.8 Hz, 2 H), 3.11 (dd,
J = 2.5, 16.8 Hz, 2 H), 3.15 (s, 2 H), 3.76 (s, 6 H), 6.31 (d, J = 3.3
Hz, 2 H), 6.71 (d, J = 3.3 Hz, 2 H), 6.74–7.10 (m, 6 H).
13C NMR (76 MHz, CDCl3): d = 26.76 (t, 2 C), 55.31 (q, 2 C), 71.75
(d, 2 C), 79.20 (s, 2 C), 110.60 (d, 2 C), 111.94 (d, 2 C), 119.62 (s,
2 C), 120.61 (d, 2 C), 125.96 (d, 2 C), 128.06 (d, 2 C), 150.16 (s, 2
C), 152.28 (s, 2 C), 152.37 (s, 2 C), 155.31 (s, 2 C); one s, 2 C not
detected.
4,5-Bis{5-[3-(trifluoromethyl)phenyl]furan-2-yl}octa-1,7-
diyne-4,5-diol (8i)
To 7i (400 mg, 836 mmol) in THF (20 mL) at –20 °C was slowly
added 1.96 M propargylmagnesium bromide in Et2O (1.71 mL, 3.35
mmol). Column chromatography (silica gel, PE–Et2O, 2:1) gave 8i
(381 mg, 682 mmol, 82%) as a yellow solid; mixture of diaste-
reomers, ratio 57:43, which could not be separated; Rf = 0.30 (PE–
Et2O, 2:1).
4,5-Bis[5-(3-methoxyphenyl)furan-2-yl]octa-1,7-diyne-4,5-diol
(8k)
To 7k (313 mg, 1.27 mmol) in Et2O (30 mL) at –10 °C was slowly
added 1.33 M propargylmagnesium bromide (3.82 mL, 5.08 mmol);
the mixture was stirred at r.t. for 4 h. Column chromatography (sil-
ica gel, PE–Et2O–CH2Cl2, 12:2:1) gave anti-8k (275 mg, 45%) and
syn-8k (146 mg, 24%) as yellow solids.
IR (film): 3517, 3303, 1332, 1263, 1165, 1120, 794, 698, 649, 617
cm–1.
1H NMR* (500 MHz, CDCl3): d = 1.97/1.97 (t, J = 2.6 Hz, 2 H/2
H), 2.97/2.99 (dd, J = 16.9, 2.6 Hz, 2 H/2 H), 3.23/3.23 (dd,
J = 16.9, 2.6 Hz, 2 H/2 H), 3.31/3.33 (br s, 2 OH/2 OH), 6.52/6.60
(d, J = 3.4 Hz, 2 H/2 H), 6.70/6.73 (d, J = 3.4 Hz, 2 H/2 H), 7.22 (t,
J = 7.7 Hz, 2 H), 7.30 (t, J = 7.9 Hz, 2 H), 7.39 (t, J = 7.8 Hz, 2 H),
7.44 (d, J = 8.1 Hz, 2 H), 7.49 (d, J = 7.9 Hz, 2 H), 7.51–7.52 (m, 2
H), 7.66 (d, J = 7.9 Hz, 2 H), 7.69–7.70 (m, 2 H).
anti-8k
Mp 42 °C; Rf = 0.14 (PE–Et2O–CH2Cl2, 12:2:1).
IR (film): 3297, 1612, 1598 1488, 1431, 1289, 1220, 1180, 1093,
1041 cm–1.
13C NMR* (126 MHz, CD2Cl2): d = 26.11/26.53 (t, 2 C/2 C), 72.10/
72.26 (d, 2 C/2 C), 77.32/77.37 (s, 2 C/2 C), 78.73/79.47 (s, 2 C/2
C), 106.93/107.18 (d, 2 C/2 C), 111.30/111.51 (d, 2 C/2 C), 119.95/
1H NMR (300 MHz, CDCl3): d = 1.74 (t, J = 2.4 Hz, 2 H), 2.74 (dd,
J = 2.5, 16.7 Hz, 2 H), 3.05 (dd, J = 2.5, 16.7 Hz, 2 H), 3.26 (br s, 2
Synthesis 2010, No. 13, 2297–2307 © Thieme Stuttgart · New York

PAPER
Gold Catalysis: Desymmetrization in the Furan–Yne Reaction
2305
H), 3.59 (s, 6 H), 6.24 (d, J = 3.3 Hz, 2 H), 6.59 (d, J = 3.3 Hz, 2 H),
version (see Table 2) the solvent was removed in vacuo;
6.90 (s, 2 H), 7.02–7.08 (m, 6 H).
purification by column chromatography (silica gel, PE–Et2O, 2:1)
gave 10a (49.2 mg, 165 mmol, 92%) as a light brown solid; mp 76–
78 °C; Rf = 0.23 (PE–Et2O, 2:1).
13C NMR (76 MHz, CDCl3): d = 26.71 (t, 2 C), 55.10 (q, 2 C), 72.02
(d, 2 C), 106.19 (d, 2 C), 109.29 (d, 2 C), 110.96 (d, 2 C), 112.99 (d,
2 C), 116.37 (d, 2 C), 129.72 (d, 2 C), 131.83 (s, 2 C), 153.52 (s, 2
C), 153.52 (s, 2 C), 159.87 (s, 2 C); two s, 2 C not detected.
IR (film): 3380, 2920, 1693, 1592, 1430, 1357, 1221, 1018, 786
cm–1.
MS (EI+, 70 eV): m/z (%) = 482 (49) [M]+, 464 (36), 425 (100), 397
(36), 347 (11), 312 (22), 291 (61), 281 (27).
HRMS (EI+, 70 eV): m/z [M]+ calcd for C30H26O6: 482.1729; found:
482.1701.
1H NMR (300 MHz, acetone-d6): d = 2.05 (s, 3 H), 2.31 (d, J = 0.6
Hz, 3 H), 2.43 (s, 3 H), 2.90 (d, J = 14.3 Hz, 1 H), 3.06 (br s, 1 OH),
3.42 (d, J = 14.3 Hz, 1 H), 4.83 (br s, 1 OH), 6.23 (dq, J = 3.3, 1.0
Hz, 1 H), 6.70 (d, J = 3.3 Hz, 1 H), 6.95 (d, J = 7.5 Hz, 1 H), 7.01
(d, J = 7.5 Hz, 1 H), 7.16 (s, 1 H).
syn-8k
1H NMR (300 MHz, CDCl3): d = 2.10 (s, 3 H), 2.21 (s, 3 H), 2.34
(s, 3 H), 2.68 (d, J = 16.5 Hz, 1 H), 3.25 (d, J = 16.5 Hz, 1 H), 4.50
(br s, 1 OH), 4.99 (br s, 1 OH), 6.06 (d, J = 3.2 Hz, 1 H), 6.56 (d,
J = 3.2 Hz, 1 H), 6.87 (d, J = 7.8 Hz, 1 H), 6.91 (d, J = 3.2 Hz, 1 H),
6.92 (s, 1 H).
13C NMR (75 MHz, acetone-d6): d = 13.60 (q), 16.22 (q), 31.58 (q),
52.58 (t), 83.25 (s), 108.61 (d), 110.34 (d), 115.37 (d), 119.52 (d),
126.05 (s), 128.44 (s), 129.04 (d), 140.17 (s), 148.95 (s), 149.38 (s),
149.48 (s), 152.74 (s), 207.20 (s).
Rf = 0.10 (PE–Et2O–CH2Cl2, 12:2:1).
1H NMR (300 MHz, CDCl3): d = 1.77 (t, J = 2.5 Hz, 2 H), 2.77 (d,
J = 16.7 Hz, 2 H), 3.07 (d, J = 16.7 Hz, 2 H), 3.26 (br s, 2 H), 3.59
(s, 6 H), 6.29 (d, J = 3.3 Hz, 2 H), 6.42 (d, J = 3.5 Hz, 2 H), 6.50 (d,
J = 8.1 Hz, 2 H), 6.93–7.02 (m, 6 H).
13C NMR (76 MHz, CDCl3): d = 26.47 (t, 2 C), 55.25 (q, 2 C), 71.87
(d, 2 C), 79.71 (s, 2 C), 105.95 (d, 2 C), 109.00 (d, 2 C), 111.19 (d,
2 C), 113.17 (d, 2 C), 116.30 (d, 2 C), 129.51 (d, 2 C), 131.57 (s, 2
C), 153.59 (s, 2 C), 153.70 (s, 2 C), 159.70 (s, 2 C); one s, 2 C not
detected.
MS (CI+, CH4): m/z (%) = 298 (100) [M]+, 281 (27), 255 (23), 240
(39), 43 (41).
HRMS (EI+, 70 eV): m/z [M]+ calcd for C18H18O4: 298.1205; found:
298.1176.
4,5-Bis(5-dimethylfuran-2-yl)octa-1,7-diyne-4,5-diol (8l)
To 7l (200 mg, 812 mmol) in Et2O (10 mL) at –10 °C was slowly
added 1.09 M propargylmagnesium bromide (2.98 mL, 3.25 mmol);
the mixture was stirred at r.t. for 4 h. Column chromatography (sil-
ica gel, PE–Et2O, 3:1) gave anti-8l (107 mg, 40%) and syn-8l (50
mg, 19%) as yellow oils.
1-[5-Ethyl-2-(5-ethylfuran-2-yl)-1,4-dihydroxy-1H-inden-1-
yl]propan-2-one (10b)
To anti-8b (30.0 mg, 91.9 mmol) in CD3CN (500 mL) was added 10
wt% AuCl3 in CD3CN soln [13.9 mg, AuCl3 (1.39 mg, 4.60 mmol, 5
mol%)]. After 24 h the solvent was removed in vacuo. Column
chromatography (silica gel, PE–Et2O, 3:1) gave 10b (28.5 mg,
95%) as a colorless oil; Rf = 0.28 (PE–Et2O, 3:1).
anti-8l
Rf = 0.40 (PE–Et2O, 3:1).
IR (film): 3287, 1699, 1670, 1559, 1540, 1520, 1421, 1377 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.95 (s, 6 H), 2.03 (t, J = 2.7 Hz,
2 H), 2.20 (s, 6 H), 2.71 (d, J = 16.7 Hz, 2 H), 3.02 (s, 2 H), 3.08 (d,
J = 16.7 Hz, 2 H), 6.17 (s, 2 H).
13C NMR (76 MHz, CDCl3): d = 10.34 (q, 2 C), 11.77 (q, 2 C),
26.58 (t, 2 C), 71.60 (d, 2 C), 80.64 (s, 2 C), 112.44 (d, 2 C), 115.08
(s, 2 C), 147.43 (s, 2 C), 150.20 (s, 2 C); one s, 2 C not detected.
MS (EI+, 70 eV): m/z (%) = 326 (3) [M]+, 267 (35), 229 (6), 108
(100).
HRMS (EI+, 70 eV): m/z [M]+ calcd for C20H22O4: 326.1518; found:
326.1488.
A similar conversion of an anti/syn mixture gave 67% yield of 10b.
IR (film): 2969, 2936, 1700, 1543, 1435, 1361, 909, 731 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.24 (t, J = 7.6 Hz, 3 H), 1.28 (t,
J = 7.3 Hz, 3 H), 2.12 (s, 3 H), 2.62 (d, J = 7.3 Hz, 2 H), 2.70 (q,
J = 7.7 Hz, 2 H), 3.23 (s, 1 H), 4.50 (br s, 1 H), 4.79 (br s, 1 H), 5.30
(s, 1 H), 6.08 (d, J = 3.4 Hz, 1 H), 6.59 (d, J = 3.2 Hz, 1 H), 6.93 (d,
J = 6.2 Hz, 2 H), 6.59 (d, J = 3.2 Hz, 1 H).
13C NMR (76 MHz, CDCl3): d = 12.14 (q), 14.10 (q), 22.77 (t),
31.95 (q), 50.43 (t), 77.21 (s), 83.01 (s), 106.30 (d), 109.91 (d),
115.34 (d), 118.21 (d), 126.90 (d), 127.52 (s), 130.68 (s), 139.28 (s),
147.00 (s), 147.76 (s), 158.32 (s), 210.70 (s).
MS (EI+, 70 eV): m/z (%) = 326 (77) [M]+, 268 (100), 253 (63), 283
(9), 213 (11), 162 (10), 151 (14).
HRMS (EI+, 70 eV): m/z [M]+ calcd for C20H22O4: 326.1518; found:
326.1491.
syn-8l
Rf = 0.23 (PE–Et2O, 3:1).
1H NMR (300 MHz, CDCl3): d = 1.85 (s, 6 H), 1.87 (t, J = 2.7 Hz,
2 H), 2.06 (s, 6 H), 2.67 (dd, J = 2.7, 16.7 Hz, 2 H), 2.89 (dd, J = 2.7,
16.7 Hz, 2 H), 3.12 (s, 2 H), 6.02 (s, 2 H).
13C NMR (76 MHz, CDCl3): d = 9.96 (q, 2 C), 11.39 (q, 2 C), 26.77
(t, 2 C), 71.22 (d, 2 C), 80.24 (s, 2 C), 112.05 (d, 2 C), 114.13 (s, 2
C), 147.04 (s, 2 C), 149.78 (s, 2 C); one s, 2 C not detected.
1-[1,4-Dihydroxy-5-phenyl-2-(5-phenylfuran-2-yl)-1H-inden-1-
yl]propan-2-one (10g)
To anti-8g (90.0 mg, 213 mmol) in anhyd CH2Cl2 (5 mL) was added
10 wt% AuCl3 in MeCN soln (32.2 mg, 10.7 mmol, 5 mol%). After
consumption of the starting material (TLC) column chromatogra-
phy gave 10g (95% yield); Rf = 0.14 (PE–Et2O, 4:1).
1H NMR (300 MHz, CDCl3): d = 2.19 (s, 3 H), 2.79 (d, J = 16.9 Hz,
1 H), 3.35 (d, J = 16.9 Hz, 1 H), 4.75 (br s, 1 OH), 5.37 (br s, 1 OH),
6.77 (d, J = 3.5 Hz, 1 H), 6.81 (d, J = 3.5 Hz, 1 H), 7.05 (d, J = 7.6
Hz, 1 H), 7.10 (d, J = 7.6 Hz, 1 H), 7.25–7.55 (m, 9 H), 7.74–7.78
(m, 2 H).
Gold-Catalyzed 5-exo-dig-Cyclization To Give Indene Deriva-
tives 10
1-[1,4-Dihydroxy-5-methyl-2-(5-methylfuran-2-yl)-1H-inden-
1-yl]propan-2-one (10a)
To anti-8a (53.3 mg, 179 mmol) in CD2Cl2 (0.7 mL) was added 10
wt% AuCl3 in CD3CN soln (27.1 mg, 8.94 mmol, 5 mol%). The re-
action progress was monitored by 1H NMR and after complete con-
Synthesis 2010, No. 13, 2297–2307 © Thieme Stuttgart · New York

2306
A. S. K. Hashmi et al.
PAPER
1-(1,4-Dihydroxy-5-[3-(trifluoromethyl)phenyl]-2-{5-[3-(tri-
fluoromethyl)phenyl]furan-2-yl}-1H-inden-1-yl)propan-2-one
(10i)
To a mixture of both diastereomers of 8i (24.5 mg, 43.8 mmol) in
CD2Cl2 (0.7 mL) was added 10 wt% AuCl3 in CD3CN (6.6 mg, 2.19
mmol, 5 mol%). An in situ 1H NMR taken after 10 min showed com-
plete conversion of the substrate; Rf = 0.30 (PE–Et2O, 2:1).
1H NMR (300 MHz, CDCl3): d = 2.19 (s, 3 H), 2.76 (d, J = 16.9 Hz,
1 H), 3.33 (d, J = 16.9 Hz, 1 H), 6.40 (d, J = 3.5 Hz, 1 H), 6.49 (d,
J = 3.5 Hz, 1 H), 6.85 (s, 1 H), 7.06 (d, J = 7.6 Hz, 1 H), 7.12 (d,
J = 7.6 Hz, 1 H), 7.22–7.98 (m, 8 H), OH-signals could not be as-
signed.
1H NMR (300 MHz, CDCl3): d = 2.08 (s, 3 H), 2.18 (s, 3 H), 2.20
(s, 3 H), 2.28 (s, 3 H), 2.32 (s, 3 H), 2.99 (d, J = 17.1 Hz, 1 H), 3.72
(d, J = 17.2 Hz, 1 H), 4.66 (s, 2 H), 6.03 (s, 1 H), 6.80 (s, 1 H), 6.96
(s, 1 H).
13C NMR (76 MHz, CDCl3): d = 11.60 (q), 19.09 (q), 20.41 (q),
53.43 (t), 70.97 (d), 97.67 (s), 106.96 (s), 118.57 (d), 124.46 (d),
137.92 (s), 140.13 (s), 140.27 (s), 150.04 (s), 162.09 (s), 204.92 (s).
MS (FAB+): m/z (%) = 326 (25) [M]+, 325 (100), 324 (58), 285 (48),
261 (50), 259 (55).
HRMS (FAB+): m/z [M]+ calcd for C20H22O4: 326.1518; found:
326.1475.
1-{1,4-Dihydroxy-5-(2-methoxyphenyl)-2-[5-(2-methoxyphe-
nyl)furan-2-yl]-1H-inden-1-yl}propan-2-one (10j)
References
To anti-8j (171 mg, 354 mmol) in CD3CN (700 mL) was added 10
wt% AuCl3 in CD3CN soln [53.7 mg, AuCl3 (5.37 mg, 17.7 mmol, 5
mol%)]. After 24 h the solvent was removed and column chroma-
tography (silica gel; PE–Et2O–CH2Cl2, 5:2:1) to give 10j (60.0 mg,
36%) as a yellow oil; Rf = 0.28 (PE–Et2O, 3:1).
(1) (a) Dyker, G. Angew Chem. Int. Ed. 2000, 39, 4237; Angew.
Chem. 2000, 112: 4407. (b) Hashmi, A. S. K. Gold Bull.
2003, 36, 3. (c) Hashmi, A. S. K. Gold Bull. 2004, 37, 51.
(d) Krause, N.; Hoffmann-Röder, A. Org. Biomol. Chem.
2005, 3, 387. (e) Hashmi, A. S. K.; Hutchings, G. Angew.
Chem. Int. Ed. 2006, 45, 7896; Angew. Chem. 2006, 118,
8064. (f) Fürstner, A.; Davies, P. W. Angew. Chem. Int. Ed.
2007, 46, 3410; Angew. Chem. 2007, 119, 3478.
IR (film): 3464, 2924, 2852, 1717, 1671, 1598, 1487 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.10 (s, 3 H), 3.26 (d, J = 16.7 Hz,
1 H), 3.71 (d, J = 16.7 Hz, 1 H), 3.86 (s, 6 H), 6.35 (s, 1 H), 6.73 (d,
J = 3.5 Hz, 1 H), 6.88 (m, 6 H), 7.34 (m, 5 H), 7.90 (d, J = 6.0 Hz,
2 H).
13C NMR (76 MHz, CDCl3): d = 14.21 (q), 21.07 (q), 26.56 (t),
2972 (q), 32.01 (q), 50.30 (t), 60.42 (t), 77.25 (s), 110.37 (d), 115.65
(d), 121.13 (d), 126.09 (d), 138.84 (s), 147.60 (s), 149.94 (s), 151.23
(s), 155.65 (s), 210.94 (s).
(g) Hashmi, A. S. K. Chem. Rev. 2007, 107, 3180.
(h) Gorin, D. J.; Sherry, B. D.; Toste, F. D. Chem. Rev. 2008,
108, 3351. (i) Jiménez-Núnez, E.; Echavarren, A. M. Chem.
Rev. 2008, 108, 3326.
(2) For a recent summary of the application in total synthesis,
see: Hashmi, A. S. K.; Rudolph, M. Chem. Soc. Rev. 2008,
37, 1766.
(3) For some selected examples, see: Weyrauch, J. W.; Hashmi,
A. S. K.; Schuster, A.; Hengst, T.; Schetter, S.; Littmann, A.;
Rudolph, M.; Hamzic, M.; Visus, J.; Rominger, F.; Frey, W.;
Bats, J. W. Chem. Eur. J. 2010, 16, 956.
MS (ESI+, 70 eV): m/z (%) = 482 (6) [M]+, 470 (65), 461 (13), 445
(25).
HRMS (ESI+, 70 eV): m/z [M + Na]+ calcd for C30H26NaO6:
505.1549; found: 505.1632.
(4) (a) Hashmi, A. S. K.; Frost, T. M.; Bats, J. W. J. Am. Chem.
Soc. 2000, 122, 11553. (b) Hashmi, A. S. K.; Frost, T. M.;
Bats, J. W. Org. Lett. 2001, 3, 3769. (c) Hashmi, A. S. K.;
Weyrauch, J. P.; Rudolph, M.; Kurpejovic, E. Angew. Chem.
Int. Ed. 2004, 43, 6545; Angew. Chem. 2004, 116, 6707.
(d) Hashmi, A. S. K.; Rudolph, M.; Weyrauch, J. P.; Wölfle,
M.; Frey, W.; Bats, J. W. Angew. Chem. Int. Ed. 2005, 44,
2798; Angew. Chem. 2005, 117, 2858. (e) Hashmi, A. S. K.;
Wölfle, M.; Ata, F.; Hamzic, M.; Salathé, R.; Frey, W. Adv.
Synth. Catal. 2006, 348, 2501. (f) Hashmi, A. S. K.;
Rudolph, M.; Siehl, H.-U.; Tanaka, M.; Bats, J. W.; Frey, W.
Chem. Eur. J. 2008, 14, 3703.
(5) (a) Hashmi, A. S. K.; Weyrauch, J. P.; Kurpejovic, E.; Frost,
T. M.; Miehlich, B.; Frey, W.; Bats, J. W. Chem. Eur. J.
2006, 12, 5806. (b) Hashmi, A. S. K.; Enns, E.; Frost, T. M.;
Schäfer, S.; Schuster, A.; Frey, W.; Rominger, F. Synthesis
2008, 2707. (c) Hashmi, A. S. K.; Rudolph, M.; Huck, J.;
Frey, W.; Bats, J. W.; Hamzic, M. Angew. Chem. Int. Ed.
2009, 48, 5848; Angew. Chem. 2009, 121, 5962.
1-{1,4-Dihydroxy-5-(3-methoxyphenyl)-2-[5-(3-methoxyphe-
nyl)furan-2-yl]-1H-inden-1-yl}propan-2-one (10k)
To anti-8k (16.0 mg, 32.2 mmol) in CD3CN (500 mL) was added 10
wt% AuCl3 in CD3CN soln [50 mg, AuCl3 (500 mg 1.66 mmol, 5
mol%)]. After 24 h the solvent was removed in vacuo, column chro-
matography (silica gel, PE–Et2O, 3:1) gave 10k (12.6 mg, 76%) as
a yellow oil; Rf = 0.16 (PE–Et2O, 3:1).
IR (film): 2923, 2852, 1717, 1598, 1584 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.21 (s, 3 H), 2.80 (d, J = 16.8 Hz,
1 H), 3.65 (d, J = 17.0 Hz, 1 H), 3.89 (s, 3 H), 3.92 (s, 3 H), 4.76 (s,
1 H), 5.53 (s, 1 H), 6.80 (m, 6 H), 7.68 (m, 7 H).
13C NMR (76 MHz, CDCl3): d = 26.92 (q), 29.70 (q), 31.25 (q),
77.23 (d), 108.50 (d), 110.02 (d), 113.55 (s), 114.01 (d), 116.49 (d),
117.12 (d), 119.97 (d), 120.04 (s), 121.04 (s), 129.82 (s), 129.93 (d),
130.63 (s), 131.11 (s), 155.81 (s), 159.94 (s), 176.05 (s), 188.62 (s),
196.31 (s).
MS (EI+, 70 eV): m/z (%) = 482 (77) [M]+.
HRMS (EI+, 70 eV): m/z [M]+ calcd for C30H26O4: 482.1729; found:
(d) Hashmi, A. S. K.; Pankajakshan, S.; Rudolph, M.; Enns,
E.; Bander, T.; Rominger, F.; Frey, W. Adv. Synth. Catal.
2009, 351, 2855. (e) For an overview on these modifications
of the reactivity pattern, see: Hashmi, A. S. K. Pure Appl.
Chem. 2010, 82, in press.
482.1688.
1-[2-(4,5-Dimethylfuran-2-yl)-1,4-dihydroxy-5,6-dimethyl-1H-
inden-1-yl]propan-2-one (10l)
To anti-8l (100 mg, 306 mmol) in CD3CN (500 mL) was added 10
wt% AuCl3 in CD3CN soln [46.5 mg, AuCl3 (4.65 mg, 15.3 mmol, 5
mol%)]. After 24 h the solvent was removed in vacuo and column
chromatography (silica gel, PE–Et2O, 3:1) gave 10l (72 mg, 72%)
as a colorless oil; Rf = 0.20 (PE–Et2O, 3:1).
(6) Hashmi, A. S. K.; Wölfle, M.; Teles, J. H.; Frey, W. Synlett
2007, 1747.
(7) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155.
(8) Organ, M. G.; Avola, S.; Dubovyk, I.; Hadei, N.; Kantchev,
E. A. B.; O’Brien, C. J.; Valente, C. Chem. Eur. J. 2006, 12,
4749.
(9) Huang, X.; Anderson, K. W.; Zim, D.; Jiang, L.; Klapars, A.;
Buchwald, S. L. J. Am. Chem. Soc. 2003, 125, 6653.
IR (film): 3439, 2983, 2922, 1678, 1438 cm–1.
Synthesis 2010, No. 13, 2297–2307 © Thieme Stuttgart · New York

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Gold Catalysis: Desymmetrization in the Furan–Yne Reaction
2307
(10) Navarro, O.; Marion, N.; Mei, J.; Nolan, S. P. Chem. Eur. J.
2006, 12, 5142.
(11) For the X-ray crystal structure analysis of a related
compound with syn-configuration (which is the meso-
diastereomer), see: Bolte, M.; Eckstein, K.; Hashmi, A. S. K.
Acta Crystallogr., Sect. E 2005, 61, o4064.
(14) (a) Hashmi, A. S. K.; Wölfle, M. Tetrahedron 2009, 65,
9021. (b) Hashmi, A. S. K.; Schwarz, L.; Rubenbauer, P.;
Blanco, M. C. Adv. Synth. Catal. 2006, 348, 705.
(15) Hashmi, A. S. K.; Hamzic, M.; Rudolph, M.; Ackermann,
M.; Rominger, F. Adv. Synth. Catal. 2009, 351, 2469.
(16) Maier, M. E. Nachr. Chem., Tech. Lab. 1993, 41, 696.
(17) Lee, C. K.; Kim, M. S.; Gong, J. S.; Lee, I.-S. J. Heterocycl.
Chem. 1992, 29, 149.
(12) Hashmi, A. S. K.; Blanco, M. C.; Kurpejovic, E.; Frey, W.;
Bats, J. W. Adv. Synth. Catal. 2006, 348, 709.
(13) Hashmi, A. S. K.; Haufe, P.; Schmid, C.; Rivas Nass, A.;
Frey, W. Chem. Eur. J. 2006, 12, 5376.
Synthesis 2010, No. 13, 2297–2307 © Thieme Stuttgart · New York