Total Synthesis of the Plant Growth Promoter Auxofuran Featuring a Gold(I) Catalyzed Furan Formation

Article abstract of DOI:10.1021/acs.joc.0c00408

A concise synthesis of auxofuran (1) was developed. Starting with a Sonogashira cross-coupling reaction, enynol (10) was prepared. A gold(I) catalyzed cycloisomerization led to disubstituted furan 12. Via an intramolecular Friedel-Crafts cyclization, a dihydrobenzofuranone was obtained. Functional group manipulations, including benzylic oxidation, led to the target molecule.

Full text of DOI:10.1021/acs.joc.0c00408

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Note
Total Synthesis of the Plant Growth Promoter Auxofuran
featuring a Gold(I) catalyzed Furan Formation
Sibylle Riedel, and Martin E. Maier
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c00408 • Publication Date (Web): 20 May 2020
Downloaded from pubs.acs.org on May 20, 2020
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The Journal of Organic Chemistry
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Total Synthesis of the Plant Growth Promoter Auxofuran featuring a
Gold(I) catalyzed Furan Formation
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†
*,†
Sibylle Riedel and Martin E. Maier
†
Eberhard Karls Universität Tübingen, Institut für Organische Chemie, Auf der Morgenstelle 18, 72076 Tübingen, Germany
Supporting Information Placeholder
CO2tBu
OH
LAu(I) cat
MeOH, r.t.
7 steps
O
O
(91%)
OH
10
12
CO2tBu
O
auxofuran (1)
ABSTRACT: A concise synthesis of auxofuran (1) was developed. Starting with a Sonogashira cross-coupling reaction, enynol (10)
was prepared. A gold(I) catalyzed cycloisomerization led to disubstituted furan 12. Via an intramolecular Friedel-Crafts cyclization,
a dihydrobenzofuranone was obtained. Functional group manipulations including benzylic oxidation led to the target molecule.
Most of the plants benefit from a symbiotic interaction with
fungi, which is called mycorrhiza. The plant can supply
compounds produced by photosynthesis to the fungus. The
fungus, in turn, can aid in obtaining minerals from the soil
surrounding the roots. Very often mycorrhiza additionally
contain bacteria that may support this symbiotic relation
between plant and fungus. These mycorrhiza helper bacteria
stimulate mycorrhiza formation and fungal growth. Some years
ago, the screening of actinomycetes from the hydrosphere of a
sprue for positive effects on symbiotic and plant-pathogenic
fungi led to the discovery of auxofuran (1) and two antifungal
Y
OH
O
3a
2
CO tBu
4
7
X
O 7a
O
OH
O
Y
1
2
X = H or Cl
Y = OR, =O or H)
3
With this plan as a guideline, we started the synthesis of
enynol 10 from 2-pentenal (4) (Scheme 2). Iodination of 4 in
9
the -position followed by reduction of the aldehyde function
1
10
compounds. Structural elucidation showed it to have a 5,6-
dihydrobenzofuran-7(4H)-one core structure (Figure 1).2
using DIBAL-H delivered allylic alcohol 6. The 5-hexynoate
11,12
9 required for the ensuing Sonogashira coupling
prepared by alkylation of tert-butyl acetate (7) with the
triflate 8, obtained from but-3-yn-1-ol. The cross-coupling
between vinyl iodide 6 and hexynoate 9 delivered enynol 10 in
excellent yield. Care must be taken that the reaction temperature
is below 10 ºC and that oxygen is excluded from the mixture.
Otherwise the diyne resulting from Glaser coupling of 9 is
formed as a side product. Treatment of enynol 10 with gold(I)
complex 11 (3 mol%) in methanol led to smooth formation of
2,4-disubstituted furan 12. With catalyst 11 a yield of 92% was
was
1
3
OH
14
4
3a
3
5
6
2
7
7
a O
O
O
O
auxofuran (1)
5,6-dihydrobenzofuran-7(4H)-one
Figure 1. Structure of (–)-auxofuran (1).
So far one total synthesis of (–)-auxofuran was described by
3 3 6
obtained. The simpler gold(I) complex [Ph PAu(NCCH )SbF ]
3
Boukouvalas et al. They used a domino Diels-Alder reaction-
gave furan 12 with 79%. Since reasonable yields were obtained
with these two catalysts, no other gold(I) complexes were
screened for the cycloisomerization of 10 to 12.
cycloreversion between an alkyne and an oxazole to prepare a
3
,4-disubstituted furan derivative. An intramolecular Friedel-
Crafts cyclization formed the C7a-C7 bond.
Scheme 2. Synthesis of furan 12 from enynol 10
In principle, the synthesis of the fused ring system might start
from a furan or a cyclohexanone derivative. In both cases, care
must be taken to prevent the formation of benzofurans by
elimination and/or tautomerization. Since we had some
4
experience with the Liu furan synthesis by gold(I)-catalyzed
5,6,7
cycloisomerization of enynols,
we chose the furan first
8
approach (Scheme 1). In this case the second ring would be
fashioned by closing the C3a-C4 bond.
Scheme 1. Plan for the synthesis of auxofuran
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O
O
I2, K2CO3, DMAP
DIBAL-H, THF
–80 °C to r.t.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
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2
2
2
2
2
2
2
2
3
3
3
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3
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3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
KOH, H2O/MeOH
r.t., 24 h (99%)
PCl5, SnCl4
H
H
THF/H2O, r.t. (94%)
toluene, 0 °C
(98%)
4
I
5
(89%)
O
O
12
14
CO2tBu
13 CO H
2
OH
CO2tBu
9
CO tBu
2
O
OH
Pd(PPh3)4, CuI, Et3N
I
6
10
NaBH4, MeOH
r.t. 3 h (99%)
Ac2O, Et3N
DMAP, r.t., 4 h
99%)
THF, 10 °C to r.t. (95%)
OH
O
O
O
(
tBu
15
LAu(I) cat. 11
MeOH, r.t. (92%)
tBu
P
11
+
Au -NCCH3 SbF6-
OAc
OAc
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
O
NBS, h, CCl4
AgBF4, DMSO
12
CO2tBu
r.t., 1 h
Et N/CCl
O
3
4
r.t., 3 h
16
17
Br
a) LDA, DMPU
THF, –80 °C
O
CO2tBu
OAc
OAc
O
OAc
O
OtBu b)
7
9
DMP, NaHCO3
CH Cl , r.t.
8
OSO2CF3
80 °C to r.t. (83%)
+
–
O
O
2
2
O
1
2 h (47%)
OH
18
19
19
Next we focused on the formation of the 6,7-
1
5
dihydrobenzofuran-4(5H)-one 14. Saponification of ester 12
gave carboxylic acid 13. Cyclization to the
dihydrobenzofuranone 14 was performed in a one-pot
procedure by conversion of the acid to the corresponding acid
chloride followed by addition of tin tetrachloride (0.2 equiv).
This way benzofuranone 14 was obtained in essentially
quantitative yield (Scheme 3). We now had to adjust the
oxidation levels at positions 4 and 7. First, ketone 14 was
reduced to alcohol 15 which then was protected with an acetate
group. The benzylic functionalization at C7 turned out to be not
easy. Eventually, it was found that radical bromination using
NBS and irradiation led to bromide 17. This sensitive
intermediate was not isolated but rather subjected to solvolysis
OH
NaHCO3, MeOH
r.t. (92%)
O
16
O
1
Instead of annulation by intramolecular Friedel-Crafts
reaction, it was also possible to form the cyclohexane ring by
intramolecular hydroxyalkylation (Scheme 4). Thus, reduction
of ester 12 using DIBAL-H in hexane provided aldehyde 20.
Upon treatment of this aldehyde with TMSOTf in presence of
18
2
,6-lutidine, silyl ether 21 was obtained. Cleavage of the silyl
ether also led to key alcohol 15.
1
7
4 3
with DMSO in presence of AgBF and Et N. These conditions
delivered a mixture of alcohol 18 and ketone 19. Treatment of
this mixture with Dess-Martin periodinane converted alcohol
Scheme 4. Alternative ring closure via hydroxyalkylation to
give silyl ether 15
1
8 to ketone 19. A final cleavage of the acetate under basic
conditions furnished auxofuran (1). Its spectral data were in full
agreement with the literature.
O
2
,3
DIBAL-H, hexane
H
O
–80 °C, 80 min
CO2tBu (99%)
O
Scheme 3. Friedel-Crafts cyclization of acid 13 to
benzofuranon 14 and adjustment of the oxidation levels to
give auxofuran (1)
12
20
OSiMe3
OH
TMSOTf, 2,6-lutidine
CH2Cl2, –80 °C
TBAF, THF
0 °C, 1 h (75%)
O
O
21
15
In conclusion, a concise synthesis of the plant growth
promoting natural product auxofuran (1) was developed. The
synthesis features a Liu furan synthesis whereby enynol 10 was
converted to 4-(furan-2-yl)butanoate 12 using a gold(I) catalyst.
A subsequent Friedel-Crafts cyclization of the derived butanoic
acid 13 led to 6,7-dihydrobenzofuran-4(5H)-one 14. Reduction
of the keto function and benzylic oxidation provided the target
molecule. Alcohol 15 could also be obtained by intramolecular
hydroxyalkylation reaction. Since enantioselective reduction of
furanone 14 might be possible, this route offers the possibility
to prepare auxofuran in an enantioselective manner.
EXPERIMENTAL SECTION
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The Journal of Organic Chemistry
General. All reactions were performed under nitrogen
orange reaction mixture was poured on ice-cooled sodium
potassium tartrate solution (1M, 500 mL) and stirred at rt until
phase separation. The organic layer was separated and the
aqueous layer extracted with ethyl acetate (3 × 500 mL). The
1
2
3
4
5
6
7
8
9
atmosphere. All solvents used in the reactions were purified
before use. The progress of the reactions was followed by using
TLC (POLYGRAM SIL G/UV254; petroleum ether/EtOAc).
Flash chromatography was performed on silica gel Silica M,
4
combined organic layers were dried over MgSO , filtered, and
0
.04–0.63 mm, from Machery-Nagel GmbH & Co. KG,
Germany. Distilled petroleum ether with a boiling range of
0−60 °C was used. Dry diethyl ether (Et O), tetrahydrofuran
and toluene were distilled from sodium and benzophenone,
whereas dry CH Cl , hexane, DMSO, DMPU and all amines
iPr NH, 2,6-lutidine, pyridine, Et N) were distilled from CaH
Furthermore, dry CCl was distilled from P and dry
concentrated under reduced pressure. Purification was carried
out either by distillation (0.29 mbar, 90 °C oil bath, 45 °C steam
temperature) or by flash chromatography (petroleum
ether/EtOAc, 10:1 + 0.1% triethylamine). The allylic alcohol 6
4
2
2
2
f
(20.8 g, 98.1 mmol, 89%) was obtained as a yellow oil. R =
1
(
2
3
2
.
0.29 (petroleum ether/EtOAc, 10:1); H NMR (400 MHz,
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
3
4
2
O
5
6 6
C D ): δ [ppm] = 0.78 (t, J = 7.6 Hz, 3H, 5-H), 1.21 (t, J = 6.7
3
5
methanol was distilled from magnesium turnings. All
commercially available compounds (abcr, Acros, Aldrich,
Fluka, Merck and TCI) were used without purification.
Photochemical reactions were performed using a KESSIL
A160WE TUNA BLUE LED lamp. The lamp was adjusted to
full intensity, white light. The lamp was fixed around 5 – 10 cm
away from the reaction flask and a cooling fan pointing towards
the reaction flask was used to keep the temperature between 20
Hz, 1H, OH), 2.01 (qdt app quint, J = 7.5 Hz, J = 1.1 Hz, 2H,
4-H), 3.86 (ddt als dd, J = 6.6 Hz, J = 1.3 Hz 1H, 1-H), 5.48
(tt, J = 6.7 Hz, J = 1.3 Hz, 1H, 3-H); C{ H} NMR (100 MHz,
): δ [ppm] = 13.0 (C-5), 29.7 (C-4), 71.8 (C-1), 108.7 (C-
2), 136.8 (C-3); HRMS (EI-SEM) m/z: calcd. for C
3
4
3
4
13
1
6 6
C D
+
•
5
H
9
OI [M]
211.9693; found 211.9713.
trifluoromethanesulfonate14
But-3-yn-1-yl
(8). Under
nitrogen atmosphere, but-3-yn-1-ol (5.00 mL, 65.9 mmol, 1
equiv) and dry pyridine (5.6 mL, 65.9 mmol, 1 equiv) were
1
13
–
(
25 °C during the reaction. H (400.160 MHZ) and
100.620 MHz) spectra were recorded on a Bruker Avance 400
III HD spectrometer. Some of the spectra were acquired on a
C
dissolved in dry CH
dropwise to a solution of trifluoromethanesulfonic anhydride
10.0 mL, 85.1 mmol,1.3 equiv) in dry CH Cl (45 mL) at 0 °C.
2 2
Cl (50 mL). This solution was added
1
13
Bruker Avance 700 spectrometer ( H NMR at 700.29 MHz, C
NMR at 176.09 MHz). C , CDCl , DMSO d6 were used as
solvents at room temperature. Peak assignments were made by
NMR spectroscopy ( H, C, DEPT-135, H,H−COSY, HSQC,
and HMBC). HRMS (ESI-TOF) analysis was performed on
Bruker maXis 4G system, whereas HRMS (EI-SEM) analysis
was performed on a MasCom Bremen MAT 95 system.
(
2
2
6
D
6
3
The reaction mixture was stirred at 0 °C for 3.5 h meanwhile
the color changed from colorless to red brown. Then the
reaction was quenched with water (250 mL). The layers were
separated and the organic layer was washed with water (3 × 100
1
13
mL), dried over MgSO
4
, filtered, and concentrated in vacuo
(300 mbar, 25 °C). The triflate was obtained as a light-brown
(Z)-2-Iodopent-2-enal (5). To a solution of aldehyde 4 (10.0
liquid (12.8 g, 63.3 mmol, 96%). It was pure enough to be used
in the next step. Purification is possible by flash
g, 119 mmol, 1.00 equiv) in a mixture of water (300 mL) and
THF (300 mL), potassium carbonate (19.9 g, 144 mmol, 1.21
equiv), DMAP (2.91 g, 23.8 mmol, 0.20 equiv) und iodine (45.4
g, 179 mmol, 1.50 eq) were added successively while stirring
the mixture. The resulting brown reaction mixture was stirred
overnight at room temperature. Then the mixture was diluted
chromatography (pentane/CH
colorless liquid. R = 0.73 (petroleum ether/DE, 1:1); H NMR
(400 MHz, CDCl
2 2
Cl , 15:1) to give the triflate as a
1
f
4
3
): δ [ppm] = 2.10 (t, J = 2.7 Hz, 2H, 4-H),
3
4
3
2.73 (dt, J = 6.7 Hz, J = 2.7 Hz, 2H, 2-H), 4.57 (t, J = 6.7 Hz,
2H, 1-H); C{ H} NMR (100 MHz, CDCl
(C-2), 71.8 (C-4), 73.5 (C-1), 76.9 (C-3), 113.8 – 123.3 (q, J =
13
1
3
): δ [ppm] = 19.9
1
with EtOAc (150 mL) and saturated Na
was added. After that, the layers were separated and the organic
layer was washed with saturated Na solution (200 mL)
2 2 3
S O solution (200 mL)
1
9
320 Hz, CF
(CF ).
tert-Butyl hex-5-ynoate13 (9). Under nitrogen atmosphere, to
a solution of iPr NH (12.3 mL, 87.4 mmol, 1.4 equiv) in dry
THF (580 mL) was added at –80 °C n-BuLi (2.5M in hexane,
5.0 mL, 87.5 mmol, 1.4 equiv) in a dropwise fashion. The
3 6 6
); F NMR (377 MHz, C D ): δ [ppm] = –75.23
2
S
2
O
3
3
and hydrochloric acid (0.1 M, 200 mL). The combined aqueous
layers were extracted with ethyl acetate (3 × 200 mL). The
combined organic layers were dried over MgSO , filtered and
4
concentrated under reduced pressure. The aldehyde 5 was
obtained as a light-brown oil (23.6 g, 112 mmol, 94%). It was
sufficiently pure to be used for the next step without further
purifications. If purification is necessary, it is possible via flash
2
3
mixture was stirred at –80 °C for 45 min to form the LDA. Then
tert-butyl acetate (9.50 mL, 71.2 mmol, 1.2 equiv) was added
and the mixture stirred for 1 h. At this point DMPU (35.5 mL,
chromatography (petroleum ether/EtOAc, 10:1
+
0.1%
2
1
94 mmol, 4.8 equiv) was introduced and stirring continued for
0 min. The color of the reaction mixture turned from colorless
triethylamine) or vacuum distillation (84 °C, 2 mbar). R
f
= 0.50
(petroleum ether/EtOAc, 5:1) starting material and product
to yellow. Finally, the crude triflate 8 (12.4 g, 61.3 mmol, 1
equiv), dissolved in dry THF (10 mL) was added. Then, the
cooling bath was removed and the mixture stirred at room
temperature overnight. The orange-red reaction mixture was
quenched by adding saturated NH Cl solution (250 mL) and
4
diluted with hexane (250 mL). The organic layer was washed
with hydrochloric acid (1M, 2 × 250 mL) and water (300 mL),
1
show the same R
f
value; H NMR (400 MHz, C
6 6
D ): δ [ppm] =
3
3
0
2
.60 (t, J = 7.5 Hz, 3H, 5-H), 1.96 (qd app quin, J = 7.4 Hz,
H, 4-H), 6.02 (t, J = 6.9 Hz, 1H, 3-H), 8.08 (bs, 1H, 1-H);
C{ H} NMR (100 MHz, C
3
1
3
1
6 6
D ): δ [ppm] = 11.9 (C-5), 30.2
(
C-4), 112.2 (C-2), 162.5 (C-3), 187.3 (C-1); HRMS (ESI-TOF)
+
m/z: calcd. for C
5 7
H OINa [M + Na] 232.9434; found 232.9434.
(Z)-2-Iodopent-2-en-1-ol (6). Under nitrogen atmosphere the
dried over MgSO
pressure. The crude ester could be purified by flash
chromatography (pentane/Et O, 20:1) or distillation (2.5 mbar,
80 °C oil bath, b.p. 46 °C). The ester 9 (8.56 g, 50.9 mmol, 83%)
4
, filtered and concentrated under reduced
crude aldehyde 5 (23.0 g, 110 mmol, 1 equiv) was dissolved in
dry THF (460 mL). The yellowish solution was cooled down to
80 °C and then DIBAL-H (1M in hexane, 165 mL, 165 mmol,
.5 equiv) was added dropwise. After complete addition, the
mixture was stirred for 20 min at –80 °C, the cooling bath was
removed, and the mixture stirred for 30 min at rt. The yellow-
2
–
1
was obtained as a colorless liquid. R
f
= 0.42 (petroleum
): δ [ppm] = 1.33 (s,
1
ether/DE, 10:1); H NMR (400 MHz, C
6
D
6
3
3 3
9H, C(CH ) ), 1.64 (tt (app quin), J = 7.1 Hz, 2H, 3-H), 1.71
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4
3
4
1
(
t, J = 2.7 Hz, 1H, 6-H), 1.95 (dt, J = 7.0 Hz, J = 2.7 Hz, 2H,
ether/EtOAc, 5:1); H NMR (400 MHz, C
6
D
6
): δ [ppm] = 0.85
), 1.43 (qt (app
3
13
1
3
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
4-H), 2.17 (t, J = 7.3 Hz, 2H, 2-H); C{ H} NMR (100 MHz,
): δ [ppm] = 18.3 (C-4), 24.5 (C-3), 28.4 (C(CH ), 34.5
(C-2), 69.8 (C-6), 80.0 (C(CH ), 83.8 (C-5), 172.2 (CO tBu).
(t, J = 7.3 Hz, 3H, 3''-H), 1.36 (s, 9H, C(CH
sext), J = 7.4 Hz, 2H, 2''-H), 1.89 (tt (app quin), J = 7.2 Hz,
2H, 3-H), 2.11 (t, J = 7.3 Hz, 2H, 2-H), 2.20 (dt, J = 7.3 Hz,
)
3
3
3
3
C
6
D
6
3
)
3
3
3
3
)
3
2
4
3
J = 0.7 Hz, 2H, 1''-H), 2.50 (t, J = 7.5 Hz, 2H, 4-H), 5.78 (bs,
tert-Butyl (E)-7-(hydroxymethyl)dec-7-en-5-ynoate (10). To
a solution of dry triethylamine (110 mL, 794 mmol, 30 equiv)
4
13
1
1
H, 3'-H), 6.97 (d, J = 1.0 Hz, 1H, 5'-H); C{ H} NMR (100
): δ [ppm] = 14.3 (C-3''), 23.8 (C-2''), 24.3 (C-3),
7.7 (C-1''), 28.0 (C-4), 28.5 (C(CH ), 35.1(C-2), 79.8
C(CH ), 107.6 (C-3'), 126.3 (C-4'), 137.9 (C-5'), 156.1 (C-2'),
72.5 (C-1); HRMS (ESI-TOF) m/z: calcd. for C15 Na [M
6 6
MHz, C D
in dry THF (120 mL) were added Pd(PPh
.05 equiv), iodopent-2-enol 6 (5.61 g, 26.4 mmol, 1 equiv),
dissolved in dry THF (60 mL), hexynoate 9 (5.00 g, 29.7 mmol,
.13 equiv), dissolved in dry THF (60 mL), and CuI (1.25 g,
.58 mmol, 0.25 eq) successively at 10 °C under an argon
3 4
) (1.59 g, 1.38 mmol,
2
3 3
)
0
(
3 3
)
1
+
24 3
H O
1
6
+
Na] 275.1618; found 275.1623.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
atmosphere. Then the yellow mixture was slowly allowed to
warm to room temperature in the water bath, initially having a
temperature of 10 °C. After 20 h, the dark-yellow mixture was
diluted with hexane (200 mL), filtered (repeatedly rinsed with
hexane), and concentrated in vacuo. The orange-brown oil was
purified by flash chromatography (petroleum ether/EtOAc, 6:1,
0.1% triethylamine) to obtain enynol 10 (6.33 g, 25.1 mmol,
4-(4-Propylfuran-2-yl)butanoic acid (13). Ester 12 (2.50 g,
9.91 mmol, 1 eq) was treated with Claisen's alkali [66 mL of a
mixture of KOH (21 g), water (15 mL) and methanol (60 mL)]
and the resulting yellow solution was stirred at room
temperature for 24 h. Then water (60 mL) was added and the
mixture extracted with diethyl ether (3 × 60 mL). This was
followed by acidification of the aqueous layer to pH = 1 using
hydrochloric acid (1M). The acidic aqueous layer was extracted
with diethyl ether (3 × 80 mL). The combined organic extracts
9
5
3
1
2
f
5%) as a light orange oil. R = 0.18 (petroleum ether/EtOAc,
1
3
:1); H NMR (400 MHz, C
6
D
6
): δ [ppm] = 0.93 (t, J = 7.1 Hz,
H, 10-H), 1.18 (t, J = 6.6 Hz, 1H, OH), 1.35 (s, 9H, C(CH ),
.70 (tt (app quin), J = 7.1 Hz, 2H, 3-H), 2.19 (t, J = 7.0 Hz,
3
3
)
3
4
(only from the acidic phase) were dried over MgSO , filtered,
and concentrated in vacuo. The acid (1.94 g, 9.89 mmol, >99%)
was obtained as a light yellow viscous oil and was pure enough
3
3
3
3
H, 4-H), 2.23 (t, J = 7.3 Hz, 2H, 2-H), 2.33 (qd (app quin), J
3
1
=
7.6 Hz, 2H, 9-H), 3.97 (d, J = 5.4 Hz, 2H, CH
2
OH), 5.70 (t,
): δ [ppm]
14.1 (C-10), 19.4 (C-4), 24.2 (C-9), 24.9 (C-3), 28.4
for the next step. R
NMR (400 MHz, DMSO d
f
= 0.41 (petroleum ether/EtOAc, 3:1); H
3
13
1
3
J = 7.3 Hz, 1H, 8-H); C{ H} NMR (100 MHz, C
6
D
6
6
3
): δ [ppm] = 0.87 (t, J = 7.3 Hz, 3H,
3''-H), 1.48 (qt (app sext), J = 7.3 Hz, 2H, 2''-H), 1.76 (tt (app
quin), J = 7.3 Hz, 2H, 3-H), 2.22 (t, J = 7.3 Hz, 2H, 2-H), 2.27
(t, J = 7.3 Hz, 2H, 1''-H), 2.54 (t, J = 7.5 Hz, 2H, 4-H), 5.98
=
3
3
(C(CH
(C(CH
3
)
)
3
), 34.7 (C-2), 66.5 (CH
), 95.0 (C-5), 124.1 (C-7), 138.0 (C-8), 172.4 (C-1);
2
OH), 78.8 (C-6), 80.1
3
3
3
3
+
4
HRMS (ESI-TOF) m/z: calcd. for C15
75.1618; found 275.1619.
di-tert-Butyl dodeca-5,7-diynedioate. If the reaction was
H
24
O
3
Na [M + Na]
(s, 1H, 3'-H), 7.23 (d, J = 0.9 Hz, 1H, 5'-H), 12.05 (s, 1H,
1
3
1
2
CO
2
H); C{ H} NMR (100 MHz, DMSO d
6
): δ [ppm] = 13.7
(
2
(
2
C-3''), 22.6 (C-2''), 23.0 (C-3), 26.4 (C-1''), 26.8 (C-4), 32.8 (C-
), 106.8 (C-3'), 125.1 (C-4'), 137.2 (C-5'), 154.9 (C-2'), 174.1
carried out at room temperature, the palladium catalyst was not
good enough, or there was oxygen present, a significant amount
of the dimeric side product as a light yellow sticky solid was
+
16 3
C-1); HRMS (ESI-TOF) m/z: calcd. for C11H O Na [M + Na]
19.0992; found 219.0990; calcd. for C11
95.1027; found 195.1031.
–
15 3
H O [M – H]
1
f
observed , and thus, the yield of the enynol 10 decreased. R =
1
0
.75 (petroleum ether/EtOAc, 5:1); H NMR (400 MHz,
3-Propyl-6,7-dihydrobenzofuran-4(5H)-one (14). Under
CDCl ): δ [ppm] = 1.43 (s, 18H, C(CH ), 1.79 (tt (app quin),
3
3
)
3
argon atmosphere, to a solution of furylbutanoic acid 13 (1.80
g, 9.17 mmol, 1 equiv) in dry toluene (92 mL) was added
phosphorus pentachloride (2.29 g, 11.0 mmol, 1.2 equiv) at 0
°C in one portion while stirring the reaction mixture with a
mechanical stirrer. The mixture was stirred at 0 °C for 1 h.
3
3
3
J = 7.3 Hz, 4H, 3-H), 2.31 (t, J = 7.0 Hz, 4H, 4-H), 2.33 (t, J
13
1
=
=
7.5 Hz, 4H, 2-H); C{ H} NMR (100 MHz, C
19.0 (C-4), 24.3 (C-3), 28.4 (C(CH ), 34.5 (C-2), 67.4 (C-
), 172.1 (C-1); HRMS (ESI-TOF)
6 6
D ): δ [ppm]
3 3
)
3 3
6), 77.3 (C-5), 80.0 (C(CH )
m/z: calcd. for C20
+
H
30
O
4
Na [M + Na] 357.2036; found
4
Thereafter, SnCl (0.1M in toluene, 18.5 mL, 1.85 mmol, 0.2
357.2039.
equiv) was added dropwise to the dark turquoise colored
solution. A dirty green precipitate formed, and the reaction
mixture was stirred at 0 °C for 17 h. The mixture was diluted
tert-Butyl 4-(4-propylfuran-2-yl)butanoate (12). Under
nitrogen atmosphere enynol 10 (4.00 g, 15.9 mmol, 1 equiv)
was dissolved in dry methanol (11 c(10) = 0.1M, B c(10) =
with CH
NaHCO
stirred at room temperature until phase separation was
observed. The aqueous layer was extracted with CH Cl (3 ×
00 mL). The combined organic layers were washed with
2
Cl
2
(100 mL), poured on a mixture of saturated
3
solution (100 mL) and ice (100 g). This mixture was
0
[
.08M) and then Au(I)-catalyst {0.477 mmol, 0.03 equiv
(acetonitrile)[(2-biphenyl)di-tert-butylphosphine]gold(I)
hexafluoroantimonate (11) (368 mg)]
(acetonitrile)[triphenylphosphine]gold(I)
2
2
or
1
[
4
saturated NaCl solution (200 mL), dried over MgSO , filtered,
and concentrated in vacuo. The light brown residue was purified
by flash chromatography (petroleum ether/EtOAc, 5:1), to give
hexafluoroantimonate (B) (351 mg)]} was added to the light
orange solution. The reaction mixture was stirred for 19 h (11)
or 24 h (B) at room temperature and then quenched with tetra-
n-butylammonium bromide (TBAB)-solution in THF (1M,
dihydrobenzofuranone 14 (1.60 g, 8.98 mmol, 98%) as a light
1
yellow oil. R
f
= 0.65 (petroleum ether/EtOAc, 3:1); H NMR
same quantity as methanol). Thereafter, Et
reach phase separation, followed by extraction of the aqueous
layer with Et O (4 × 200 mL). The combined organic layers
were dried over MgSO , filtered, and concentrated in vacuo.
The light yellow oil was purified by flash chromatography
2
O was added to
3
(
3
400 MHz, CDCl ): δ [ppm] = 0.93 (t, J = 7.3 Hz, 3H, 3'-H),
.59 (qt (app sext), J = 7.3 Hz, 2H, 2'-H), 2.13 (tt (app quin),
J = 6.5 Hz, 2H, 6-H), 2.45 (t, J = 7.0 Hz, 2H, 5-H), 2.57 (t, J
7.5 Hz, 2H, 1'-H), 2.82 (t, J = 6.3 Hz, 2H, 7-H), 7.06 (s, 1H,
3
1
2
3
3
3
4
3
=
1
3
1
2
2
1
3
-H); C{ H} NMR (100 MHz, CDCl ): δ [ppm] = 13.8 (C-3'),
(
(
petroleum ether/EtOAc, 10:1) to give furan derivative 12
using 11: 3.69 g, 14.63 mmol, 92%; using catalyst B: 3.17 g,
2.3 (C-2'), 22.7 (C-6), 23.7 (C-7), 26.1 (C-1'), 38.4 (C-5),
20.0 (C-3a), 124.2 (C-3), 138.6 (C-2), 167.6 (C-7a), 195.4 (C-
1
f
2.56 mmol, 79%) as a colorless liquid. R = 0.77 (petroleum
ACS Paragon Plus Environment

Page 5 of 7
The Journal of Organic Chemistry
4
); HRMS (ESI-TOF) m/z: calcd. for C11
201.0886; found 201.0888.
-Propyl-4,5,6,7-tetrahydrobenzofuran-4-ol (15). To
H
14
O
2
Na [M + Na]+
for 2.5 h. The mixture was diluted with ethyl acetate (10 mL)
and filtered through a plug of silica. The filtrate was
concentrated in vacuo. The light brown residue was dissolved
in dry CH Cl (50 mL) and NaHCO (340 mg, 4.05 mmol, 5
2 2 3
equiv) and DMP (515 mg, 1.21 mmol, 1.5 equiv) were added.
The reaction mixture was stirred at room temperature overnight
1
2
3
4
5
6
7
8
9
3
a
solution of ketone 14 (650 mg, 3.65 mmol, 1 equiv) in dry
methanol (15 mL), stirred at 0 °C and kept under nitrogen
atmosphere, was added NaBH
portionwise. The mixture was stirred at room temperature for 3
h. Then water (15 mL) was added and CH Cl to reach phase
separation. The aqueous layer was extracted with CH Cl (3 ×
0 mL) The combined organic layers were dried over MgSO
filtered, and concentrated in vacuo. The alcohol 15 (657 mg,
.64 mmol, >99%) was obtained as a colorless oil which can
solidify in the freezer. If purification is necessary, it is possible
4
(83.0 mg, 2.19 mmol, 0.6 equiv)
before it was quenched with saturated Na
saturated NaHCO solution (60 mL, 1:1). The aqueous layer
was extracted with CH Cl (3 × 50 mL), the combined organic
layers were dried over MgSO , filtered, and concentrated in
vacuo. The brown oil was purified by flash chromatography
petroleum ether/EtOAc, 8:1, 0.1% TEA). The ketone 19 (89.1
mg, 0.377 mmol, 47%) was isolated as a yellowish oil. R
(alcohol) = 0.32 (petroleum ether/EtOAc, 3:1); R (ketone) =
0.38 (petroleum ether/EtOAc, 3:1); H NMR (700 MHz, C ):
δ [ppm] = 0.76 (t, J = 7.3 Hz, 3H, 3'-H), 1.27 (qt (app sext),
2 2 3
S O solution and
3
2
2
2
2
2
2
4
2
4
,
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
3
f
f
via flash chromatography (petroleum ether/EtOAc, 6:1). R
f
=
):
1
1
6 6
D
0
.48 (petroleum ether/EtOAc, 5:1); H NMR (400 MHz, C
6
D
6
3
3
δ [ppm] = 0.93 (t, J = 7.3 Hz, 3H, 3'-H), 1.30 – 1.39 (m, 1H, 7-
H), 1.41 – 1.46 (m, 1H, 5-H), 1.53 – 1.65 (m, 4H, 2'-H, 5-H, 7-
H), 2.17 – 2.24 (m, 1H, 6-H), 2.32 – 2.45 (m, 3H, 1'-H, 6-H),
2
2
H, 2'-H), 1.61 (s, 3H, OCOCH
3
), 1.70 – 1.76 (m, 2H, 5-H),
2
3
.04 – 2.14 (m, 3H, 1'-H, 6-H), 2.42 (ddd, J = 17.0 Hz, J = 9.0
3
3
3
13
1
Hz, J = 5.2 Hz, 1H, 6-H), 5.87 (dd (app t), J = 4.6 Hz, 1H, 4-
4
.50 (t, J = 4.0 Hz, 1H, 4-H), 6.95 (s, 1H, 2-H); C{ H} NMR
1
3
1
H), 6.77 (bs, 1H, 2-H); C{ H} NMR (176 MHz, C
ppm] = 14.2 (C-3'), 20.7 (OCOCH ), 23.2 (C-2'), 25.7 (C-1'),
0.6 (C-5), 35.1 (C-6), 64.9 (C-4), 125.7 (C-3), 135.2 (C-3a),
144.6 (C-2), 149.3 (C-7a), 169.8 (OCOCH ), 184.5 (C-7);
6 6
D ): δ
(100 MHz, C ): δ [ppm] = 14.6 (C-3'), 18.9 (C-7), 23.4 (C-
6 6
D
[
3
3
2
1
'), 23.9 (C-6), 26.6 (C-1'), 33.4 (C-5), 63.3 (C-4), 120.8 (C-3),
25.2 (C-3a), 137.8 (C-2), 153.2 (C-7a); HRMS (EI-SEM) m/z:
+
•
3
16 2
calcd. for C11H O [M] 180.1145; found 180.1155.
+
16 4
HRMS (ESI-TOF) m/z: calcd. for C13H O Na [M + Na]
3
-Propyl-4,5,6,7-tetrahydrobenzofuran-4-yl acetate (16). To
a solution of alcohol 15 (584 mg, 3.24 mmol, 1 equiv) in dry
Et N (5.90 mL, 42.6 mmol, 13.1 eq) was added acetic anhydride
0.86 mL, 9.10 mmol, 2.8 eq) under a nitrogen atmosphere.
259.0941; found 259.0942.
Auxofuran (1). Under nitrogen atmosphere, acetate 19 (29.6
mg, 0.125 mmol, 1 equiv) was dissolved in dry methanol (1.25
3
(
mL). NaHCO
the mixture was stirred at room temperature for 4 h. The orange
reaction mixture was quenched by adding saturated NH Cl
3
(10.5 mg, 0.125 mmol, 1 equiv) was added and
Finally, a spatula of DMAP was added and the reaction mixture
was stirred at room temperature for 3.5 h. Then the mixture was
diluted with methanol (10 mL) and water (60 mL) before ethyl
acetate was added, and the layers were separated. The aqueous
layer was extracted with ethyl acetate (3 × 50 mL) The
combined organic layers were dried over MgSO , filtered, and
4
concentrated in vacuo. The yellow oil was purified by flash
chromatography (petroleum ether/EtOAc, 30:1). The acetate 16
4
solution (2 mL) and ethyl acetate was added to reach phase
separation. The aqueous layer was extracted with EtOAc (3 × 2
mL). The combined organic layers were dried over MgSO ,
4
filtered, and concentrated in vacuo. The yellow oil was purified
by flash chromatography (petroleum ether/EtOAc, 2:1) to give
auxofuran (1) (22.3 mg, 0.115 mmol, 92%) as a colorless oil. R
= 0.39 (petroleum ether/EtOAc, 1:1); H NMR (700 MHz,
f
(717 mg, 3.23 mmol, >99%) was obtained as a colorless oil. R
f
1
1
=
C
0.69 (petroleum ether/EtOAc, 5:1); H NMR (400 MHz,
3
3
CDCl
3
): δ [ppm] = 0.96 (t, J = 7.3 Hz, 3H, 3'-H), 1.62 (qt (app
6 6
D ): δ [ppm] = 0.88 (t, J = 7.3 Hz, 3H, 3'-H), 1.28 – 1.36 (m,
2
3
sext), 2H, 2'-H), 2.11 (bs, 1H, OH), 2.17 (dddd, J = 18.1 Hz, J
= 10.6 Hz, J = 6.0 Hz, J = 4.5 Hz, 1H, 5-H), 2.38 (dddd (ddd),
1
6
H, 6-H), 1.44 – 1.55 (m, 3H, 2'-H, 5-H), 1.32 – 1.69 (m, 1H,
-H), 1.72 (s, 3H, OCOCH ), 1.75 – 1.81 (m, 1H, 5-H), 2.11 –
3
3
3
2
3
3
J = 17.6 Hz, J = 8.6 Hz, J = 4.5 Hz, 1H, 5-H), 2.46 – 2.54 (m,
2.19 (m, 1H, 7-H), 2.24 – 2.32 (m, 2H, 1'-H), 2.33 – 2.39 (m,
1H, 7-H), 6.06 (t, J = 3.7 Hz, 1H, 4-H), 6.92 (s, 1H, 2-H);
2
3
3
3
3H, 1'-H, 6-H), 2.86 (ddd, J = 17.0 Hz, J = 8.6 Hz, J = 4.5
3
3
1
3
1
Hz, 1H, 6-H), 5.01 (dd, J = 5.8 Hz, J = 4.1 Hz, 1H, 4-H), 7.37
C{ H} NMR (100 MHz, C
C-6), 21.2 (OCOCH ), 23.4 (C-2'), 23.6 (C-7), 26.40 (C-1'),
0.0 (C-5), 65.6 (C-4), 117.2 (C-3a), 124.9 (C-3), 138.1 (C-2),
54.9 (C-7a), 170.2 (OCOCH ); HRMS (EI-SEM) m/z: calcd.
[M] 222.1250; found 222.1216.
6 6
D ): δ [ppm] = 14.4 (C-3'), 19.3
1
3
1
(
1
(
bs, 1H, 2-H); C{ H} NMR (176 MHz, CDCl
3.9 (C-3'), 22.7 (C-2'), 25.4 (C-1'), 33.8 (C-5), 34.5 (C-6), 63.6
C-4), 125.9 (C-3), 139.2 (C-3a), 144.8 (C-2), 147.0 (C-7a),
185.8 (C-7); HRMS (ESI-TOF) m/z: calcd. for C11 Na [M
3
): δ [ppm] =
(
3
1
3
3
+
•
14 3
H O
18 3
for C13H O
+
+
Na] 217.0835; found 217.0836.
7
-Oxo-3-propyl-4,5,6,7-tetrahydrobenzofuran-4-yl acetate
19). Under argon atmosphere acetate 16 (200 mg, 0.900 mmol,
.1 equiv) was dissolved in dry CCl (20 mL, dried over neutral
4
-(4-Propylfuran-2-yl)butanal (20). To
a solution of
(
1
furanylbutanoate 12 (690 mg, 2.73 mmol, 1 equiv) in dry
hexane (30 mL) was added DIBAL-H (1M in hexane, 2.75 ml,
2.75 mmol, 1.01 equiv) dropwise at –80 °C under nitrogen
atmosphere. The reaction mixture was stirred for 75 min at –80
°C. Then dry methanol (4 mL) was added and the light yellow
solution was poured on ice-cooled sodium potassium tartrate
solution (1M, 40 mL). This mixture was stirred at room
temperature until phase separation was observed. The aqueous
4
aluminium oxide directly before use) at room temperature. This
was followed by the addition of yellowish N-bromosuccinimide
(NBS, 144 mg, 0.809 mmol, 1 equiv). The mixture was
irradiated (white light including 621 nm) for 1 h during which
succinimide appeared as a white precipitate on the top of the
solution. The irradiation was discontinued and then DMSO (2
mL, 28.2 mmol, 34.8 equiv, dried over neutral aluminium oxide
directly before use), and AgBF (157 mg, 0.809 mmol, 1 equiv)
4
were added. This caused immediate precipitation of silver
bromide. The mixture was stirred at room temperature for 30
layer was extracted with CH
organic layers were dried over MgSO
2
Cl
2
(3 × 40 mL). The combined
filtered, and
4
,
concentrated under reduced pressure. The residue was purified
by flash chromatography (petroleum ether/EtOAc, 6:1, 0.1%
min before Et
3
N (0.25 mL, 1.80 mmol, 2.2 equiv) was added.
Et
3
N) to give aldehyde 20 (492 mg, 2.73 mmol, > 99%) as a
After that, the reaction mixture was stirred at room temperature
1
light yellow oil. H NMR (400 MHz, CDCl
3
): δ [ppm] = 0.92
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 7
3
3
(
t, J = 7.5 Hz, 3H, 3''-H), 1.53 (qt (app sext), J = 7.5 Hz, 2H,
ORCID
3
3
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
2''-H), 1.95 (tt (app quin), J = 7.2 Hz, 2H, 3-H), 2.31 (t, J =
7.3 Hz, 2H, 1''-H), 2.46 (dt, J = 7.2 Hz, J = 1.5 Hz, 2H, 2-H),
2.62 (t, J = 7.2 Hz, 2H, 4-H), 5.88 (bs, 1H, 3'-H), 7.06 (d, J =
.0 Hz, 1H, 5'-H), 9.74 (t, J = 1.6 Hz, 1H, 1-H); C{ H} NMR
100 MHz, CDCl ): δ [ppm] = 13.8 (C-3''), 20.6 (C-3), 23.1 (C-
''), 27.0 (C-1''), 27.3 (C-4), 43.0 (C-2), 107.2 (C-3'), 125.9 (C-
'), 137.2 (C-5'), 154.8 (C-2'), 202.1 (C-1);
Martin E. Maier: 0000-0002-3570-4943
3
4
3
4
ACKNOWLEDGMENT
Financial support by the state of Baden-Württemberg is gratefully
acknowledged. We also acknowledge contributions from the
students Jan Grammel and Cornelia Warmutz.
4
13
1
1
(
2
4
3
1H NMR (400 MHz, C
D
): δ [ppm] = 0.87 (t, J = 7.3 Hz,
3
6
6
REFERENCES
3
3
(
H, 3''-H), 1.46 (qt (app sext), J = 7.5 Hz, 2H, 2''-H), 1.64 (tt
app quin), J = 7.3 Hz, 2H, 3-H), 1.77 (t, J = 7.3 Hz, 2H, 2-
H), 2.21 (t, J = 7.3 Hz, 2H, 1''-H), 2.33 (t, J = 7.5 Hz, 2H, 4-
H), 5.72 (bs, 1H, 3'-H), 6.98 (d, J = 1.0 Hz, 1H, 5'-H), 9.20 (t,
3
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
3
4
1
Riedlinger, J.; Schrey, S. D.; Tarkka, M. T.; Hampp, R.; Kapur,
4
13
1
J = 1.3 Hz, 1H, 1-H); C{ H} NMR (100 MHz, C
13.9 (C-3''), 20.7 (C-3), 23.5 (C-2''), 27.3 (C-1''), 27.5 (C-4),
42.8 (C-2), 107.3 (C-3'), 125.9 (C-4'), 137.5 (C-5'), 155.4 (C-
2'), 200.1 (C-1); HRMS (ESI-TOF) m/z: calcd. for C12 Na
6 6
D ): δ [ppm]
M.; Fiedler, H.-P. Auxofuran, a Novel Metabolite That Stimulates the
Growth of Fly Agaric, Is Produced by the Mycorrhiza Helper
Bacterium Streptomyces Strain AcH 505. Appl. Environ. Microbiol.
2006, 72, 3550–3557.
=
20 3
H O
+
2
[M + CH
3
OH + Na] 235.1305; found 235.1304.
Keller, S.; Schneider, K.; Süssmuth, R. D. Structure Elucidation of
Auxofuran, a Metabolite Involved in Stimulating Growth of Fly
Agaric, Produced by the Mycorrhiza Helper Bacterium Streptomyces
AcH 505. J. Antibiot. 2006, 59, 801–803.
3-Propyl-4,5,6,7-tetrahydrobenzofuran-4-ol
(15)
aldehyde 20. To a solution of aldehyde 20 (180 mg, 0.999
mmol, 1 equiv) in dry CH Cl (15 mL) was added 2,6-lutidine
0.780 mL, 4.99 mmol, 5 equiv) at –80 °C. This was followed
by the dropwise addition of TMSOTf (1M in CH Cl , 2.50 mL,
.50 mmol, 2.5 equiv) at –80 °C. The reaction mixture was
stirred for 20 h at –80 °C. Then water (15 mL) was added and
the mixture was warmed to room temperature. The aqueous
2
layer was extracted with Et O (3 × 15 mL). The combined
from
1
8
2
2
3
Boukouvalas, J.; Loach, R. P. Concise Total Synthesis of (–)-
(
Auxofuran by a Click Diels–Alder Strategy. Org. Lett. 2013, 15, 4912–
2
2
4914.
4
2
Liu, Y.; Song, F.; Song, Z.; Liu, M.; Yan, B. Gold-Catalyzed
Cyclization of (Z)-2-En-4-yn-1-ols:ꢀ Highly Efficient Synthesis of
Fully Substituted Dihydrofurans and Furans. Org. Lett. 2005, 7, 5409–
5412. (b) Du, X.; Song, F.; Lu, Y.; Chen, H.; Liu, Y. A general and
efficient synthesis of substituted furans and dihydrofurans via gold-
catalyzed cyclization of (Z)-2-en-4-yn-1-ols. Tetrahedron 2009, 65,
organic layers were dried over MgSO
concentrated under reduced pressure.
4
, filtered, and
1
839–1845.
5
To the crude TMS-protected alcohol 21 (255 mg) in dry THF
20 mL) was added TBAF (1M in THF, 1.50 mL, 1.50 mmol,
.5 equiv) dropwise at 0 °C under nitrogen atmosphere followed
by stirring of the mixture for 1 h at 0 °C. Thereafter, the mixture
was dry-loaded on silica and purified by flash chromatography
(petroleum ether/EtOAc, 6:1) to provide alcohol 15 (135 mg,
Riedel, S.; Maichle-Mössmer, C.; Maier, M. E. Intramolecular
(
1
Diels-Alder Reactions of Tethered Enoate Substituted Furans Induced
by Dialkylaluminium Chloride. J. Org. Chem. 2017, 82, 12798–12805.
6
For other examples of gold-catalyzed furan formation, see: (a)
Hashmi, A. S. K.; Schwarz, L.; Choi, J.-H.; Frost, T. M. A New Gold-
Catalyzed C–C Bond Formation. Angew. Chem. 2000, 112, 2382–
2
385. (b) Hashmi, A. S. K.; Sinha, P. Gold Catalysis: Mild Conditions
0
.749 mmol, 75 %) as a colorless viscous oil.
for the Transformation of Alkynyl Epoxides to Furans. Adv. Synth.
Catal. 2004, 346, 432–438. (c) Hashmi, A. S. K.; Häffner, T.; Rudolph,
M.; Rominger, F. Cyclization of 2-Alkynylallyl Alcohols to Highly
Substituted Furans by Gold(I)–Carbene Complexes. Eur. J. Org. Chem.
1
Silyl ether 21: R
f
= 0.90 (petroleum ether/EtOAc, 5:1); H
): δ [ppm] = 0.17 (s, 9H, Si(CH ), 0.95
t, J = 7.3 Hz, 3H, 3'-H), 1.36 – 1.44 (m, 1H, 7-H), 1.53 – 1.68
NMR (400 MHz, C
6
D
6
3 3
)
3
(
(
1
1
2
011, 667–671. (d) Wang, T.; Shi, S.; Hansmann, M. M.; Rettenmeier,
E.; Rudolph, M.; Hashmi, A. S. K. Synthesis of Highly Substituted 3-
Formylfurans by Gold(I)-Catalyzed Oxidation/1,2-Alkynyl
Migration/Cyclization Cascade. Angew. Chem. Int. Ed. 2014, 53,
715–3719. (e) Wang, T.; Shi, S.; Rudolph, M.; Hashmi, A. S. K.
m, 4H, 2'-H, 5-H), 1.79 – 1.89 (m, 1H, 7-H), 2.36 – 2.34 (m,
3
H, 6-H), 2.39 – 2.50 (m, 3H, 1'-H, 6-H), 4.75 (t, J = 4.7 Hz,
a
1
3
1
H, 4-H), 7.00 (s, 1H, 2-H); C{ H} NMR (100 MHz, C
6 6
D ):
3 3
δ [ppm] = 0.7 (Si(CH )
), 14.2 (C-3'), 19.2 (C-7), 23.2 (C-2'),
3.5 (C-6), 26.5 (C-1'), 33.6 (C-5), 64.7 (C-4), 120.5 (C-3),
24.9 (C-3a), 137.4 (C-2), 152.5 (C-7a); HRMS (ESI-TOF)
3
2
1
Synthesis of Fully Substituted 3-Formyl-4-iodofurans via a Gold(I)-
Catalyzed Oxidation/1,2-Alkynyl Migration/Cyclization/Iodination
Cascade. Adv. Synth. Catal. 2014, 356, 2337–2342.
+
24 2
m/z: calcd. for C14H O SiNa [M + Na] 275.1438; found
7
275.1441.
For reviews, see: (a) Patil, N. T.; Yamamoto, Y. Coinage Metal-
Assisted Synthesis of Heterocycles. Chem. Rev. 2008, 108, 3395–3442.
(b) Moran, W. J.; Rodríguez, A. Metal-catalyzed Furan Synthesis. A
ASSOCIATED CONTENT
Supporting Information
Review. Org. Prep. Proc. Intl. 2012, 44, 103–130.
8
For recent reviews on gold catalysis in natural product synthesis,
see: (a) Pflästerer, D.; Hashmi, A. S. K. Gold catalysis in total synthesis
- recent achievements. Chem. Soc. Rev. 2016, 45, 1331–1367. (b)
Quach, R.; Furkert, D. P.; Brimble, M. A. Gold catalysis: synthesis of
spiro, bridged, and fused ketal natural products. Org. Biomol. Chem.
The Supporting Information is available free of charge on the ACS
Publications website. The Supporting Information is available at
https://pubs.acs.org/doi/10.1021/acs.joc.yyyy.
2
017, 15, 3098–3104. (c) Mato, M.; García-Morales, C.; Echavarren,
Copies of H and 13C NMR spectra for the synthesized compounds
1
A. M. Generation of Gold(I) Carbenes by Retro-Buchner Reaction:
From Cyclopropanes to Natural Products Synthesis. ChemCatChem
(
PDF)
2
019, 11, 53–72.
AUTHOR INFORMATION
Corresponding Author
9
Krafft, M. E.; Cran, J. W. A Convenient Protocol for the α-
Iodination of α,β-Unsaturated Carbonyl Compounds with I
Aqueous Medium. Synlett 2005, 1263–1266.
2
in an
10
*
E-mail: martin.e.maier@uni-tuebingen.de
For an alternative preparation of 6, see: Taber, D. F.; Sikkander,
M. I.; Berry, J. F.; Frankowski, K. J. Preparation of 2-Iodo Allylic
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For a review, see: Chinchilla, R.; Nájera, C. Recent advances in
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2
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1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
4
Čížková, M.; Šaman, D.; Koval, D.; Kašička, V.; Klepetářová, B.;
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1
5
According to: Wenkert, E.; Decorzant, R.; Näf, F. A Novel Access
to Ionone-Type Compounds: (E)-4-oxo-β-ionone and (E)-Oxo-β-irone
via metal-catalyzed intramolecular reactions of α-diazo ketones with
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16
Taylor, D. A. H. 555. Some experiments with furans. J. Chem.
Soc. 1959, 2767–2769.
1
7
Method adapted from: Guo, Y.; Quan, T.; Lu, Y.; Luo, T.
Enantioselective Total Synthesis of (+)-Wortmannin. J. Am. Chem.
Soc. 2017, 139, 6815–6818.
1
8
Mace, L. H.; Shanmugham, M. S.; White, J. D.; Drew, M. G. B.
A new route to furanoeremophilane sesquiterpenoids. Synthesis of
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