Gold catalysis: Oxepines from y-alkynylfurans

Article abstract of DOI:10.1002/adsc.200600653

A ketal group in a furyl position affords arene oxides from y-alkynylfurans even with the simple gold(III) chloride (AuCl₃) catalyst. These can either undergo Diels-Alder reactions, isomerise to stable oxepines by an oxygen-walk reaction or by

Full text of DOI:10.1002/adsc.200600653

FULL PAPERS
DOI: 10.1002/adsc.200600653
Gold Catalysis: Oxepines from g-Alkynylfurans
a,
a
a
a
´
A. Stephen K. Hashmi, * Elzen Kurpejovic, Michael Wçlfle, Wolfgang Frey,
and Jan W. Batsa
a
Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany
Fax: (+49)-711-685-64321; e-mail: hashmi@hashmi.de
Received: December 29, 2006
Dedicated to Prof. Dr. Peter Hofmann on the occasion of his 60th birthday.
Abstract: A ketal group in a furyl position affords the furan, the 2-hydroxymethylpyridinato-gold
arene oxides from g-alkynylfurans even with the complex, not the usual arene oxide but an oxepine is
simple gold(III) chloride (AuCl3) catalyst. These can obtained, still the arene oxide can be trapped from
(III)
ACHTREUNG
either undergo Diels–Alder reactions, isomerise to the valence-tautomeric equilibrium by a Diels–Alder
stable oxepines by an oxygen-walk reaction or by the reaction.
addition of water selectively be converted to phenols
which differ in the position of the hydroxy group
from the normal phenols formed in the gold-cata- Keywords: alkynes; furans; gold; heterocycles; ho-
lysed phenol synthesis. With a phenyl substituent on mogeneous catalysis; oxepines
Introduction
Here we report further findings concerning the par-
ticipation of arene oxides and oxepines in these reac-
Gold catalyst have recently attracted much atten- tions.
tion.[1,2] Among the new achievements in homogene-
ous gold-catalysed reactions,[2] the gold-catalysed
phenol synthesis[3] has added a new pathway to the
family of the enyne cycloisomerisations.
In these reactions an w-alkynyl furan 1, which pos-
sesses a 1,6-enyne substructure (bold in 1), furnishes a
phenol 2 (Scheme 1). Mechanistic investigations re-
vealed the close relationship to other gold-catalysed
reactions of 1,6-enynes, with the formation of cyclo-
propyl carbenoids 3 being the initial step.[4] Then the
reaction pathway diverts from that of the other enyne
cycloisomerisations, a subsequent ring-opening pro-
vides the conjugated carbenoid 4 which cyclises to the
oxepine 5, the latter is in a valence tautomeric equi-
librium with the corresponding arene oxide 6. Finally,
the regioselective ring-opening of 6 leads to 2.[5]
Side products in platinum-[5] and gold-catalysed[3k]
reactions of substrates of type 1 provided evidence
for the intermediate 4, computational chemistry[5]
confirmed the other intermediates. The first mecha-
nistic experiments had already revealed the intramo-
lecular migration of the furan oxygen to become the
phenolic oxygen atom,[3a] but only with the pre-cata-
lyst 7 (Scheme 2) could up to 80% of an arene oxide
6 be observed by in situ NMR spectroscopy and inter-
cepted by a Diels–Alder reaction to afford the stable,
Scheme 1. The gold-catalyzed phenol synthesis (X=CR2,
NR, O, CR2CR2, NRCR2, OCR2).
diastereomerically pure and crystalline oxirane 8.[3g]
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Scheme 2. Catalyst 7 selectively led to an oxirane which
could be trapped as Diels–Alder adduct 8.
Results and Discussion
The substrate 12 was prepared from 2-acetylfuran 9
by protection of the carbonyl group as ethylene glycol
ketal 10, formylation to 11 and a subsequent one-pot
sequence of an imine formation with propargylamine,
reduction to the secondary amine and N-tosylation
(Scheme 3). Both ethylene glycol ketals 11 and 12
Figure 1. Structures of aldehyde 11 (top) and substrate 12
gave single crystals for crystal structure investigation (bottom) in the solid state.
(Figure 1),[6] which show that in both one C O bond
À
of the ketal group is oriented parallel to the p-system
of the furan ring. In 12 the alkyne subunit (C-11/C-
The first gold-catalysed reaction of the ketal 12 was
12) has a large distance to the furan ring (C-1 to C-4, disappointing; instead of the formation of the expect-
O-1), a conformation which is typical for these sub- ed phenol 14, a quantitative deprotection of the ketal
strates.[3l]
to 13 was observed (88% yield after work-up,
Scheme 4). Usually, water does not disturb the phenol
Scheme 4. AuCl3 efficiently catalyzes the deprotection of
ketal 12.
synthesis,[3a] but with the reactive benzyl-like ketal it
does. After the deprotection the acetyl substituent on
the furan ring prevents a gold-catalysed phenol syn-
thesis, this effect of acceptors in the phenol synthesis
has been reported previously.[3l]
A similar experiment with 5 mol% AuCl3 in abso-
1
lute solvent and monitoring by H NMR showed that
traces of water still present led to a fast initial depro-
tection to a small extent, but once the water was con-
sumed, a new set of signals was observed in the
1H NMR spectra.
Work-up by column chromatography afforded four
products: ketone 13, phenol 15 and two unknown
products. The spectra of these unknown products sug-
gested for one of them the arene oxide structure 16,
for the other the oxepine structure 17 (Scheme 5).
The arene oxide could not be isolated in pure form
Scheme 3. Synthesis of substrate 12.
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Gold Catalysis: Oxepines from g-Alkynylfurans
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Scheme 6. Oxygen-walk to oxepine 18.
Opening of the oxirane ring of 16 gives the cyclo-
hexadienyl cation 19, which closes to the isomeric
arene oxide 20. The latter obviously is less stable than
its valence tautomer 17, in the literature there are nu-
merous examples for one valence tautomer being
clearly favoured.[10]
Scheme 5. Phenols 14 and 15, arene oxide 16 and constitu-
tional isomeric oxepines 17 and 18 (ratio in the crude reac-
tion mixture of the reaction of 12 with AuCl3 in absolute sol-
1
vent determined by H NMR; 13:15:16=2:1:8).
The structural assignment of the arene oxide was
more difficult; in solution the species was stable for a
and seemed to isomerise to the oxepine product on long time, but it rearranged on all efforts to isolate it.
the chromatography column. This was not in accor- Finally, besides precipitation at low temperatures (no
dance with the structures 16 and 17, which should be single crystals were obtained), we succeeded in trap-
valence tautomers that equilibrate.
ping it by a hetero-Diels–Alder reaction, which fur-
Most fortunately, single crystals of the assumed ox- nished the epoxide 21 and thus confirmed the struc-
epine could be obtained. The crystal structure analysis ture suggested for 16 (Scheme 7). At room tempera-
clearly proved an oxepine structure, which was not 17
but rather its constitutional isomer 18 (Figure 2).[6]
Scheme 7. Trapping of arene oxide 16.
ture the cycloaddition was instantaneous and could
conveniently be monitored by the loss of the red
colour of the N-phenyltriazolindione. Again, a crystal
Figure 2. Structure of oxepine 18 in the solid state.
structure analysis unambiguously proved the constitu-
The migration of an oxygen atom in an arene tion of the cycloadduct 21 (Figure 3).[6]
oxide/oxepine system is well known in the literature
The spectroscopic data for 16 are clearly in accord-
as “oxygen walk”;[7] in earlier work Vogel and Günth- ance with an arene oxide structure, the epoxide
er[8] have investigated related rearrangements. Kinetic proton at 4.10 ppm and the two vinylic protons at 6.30
investigations of Bruice et al.[9] proved that rather and 6.47 ppm showing an cis-olefin-like JH,H of
3
than an isomerisation to a dienone, the “oxygen 9.80 Hz. These values are in good accordance with
walk” was the major route to the isomerisation prod- the previously reported arene oxide leading to 8
ucts.
This mechanistic concept can explain the formation there, the hydrogen atoms of the methylene groups
(3.87 ppm for the epoxide proton).[3g] As described
of oxepine 18, too (Scheme 6).
are also non-equivalent and show a geminal coupling.
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A. Stephen K. Hashmi et al.
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Scheme 9. Selective fragmentation to phenol 15.
ethylene glycol acetal can be used as a directing
group.
Next we tested the reaction of substrate 23. When
subjected to the pre-catalyst 7, initially the oxepane
24 was observed (Scheme10). The oxepane structure
Figure 3. Structure of the Diels–Alder adduct 21 in the solid
state.
When D2O was added to the reaction mixture after
a full conversion of 12 to 16, a fast (about 30 min re-
action time) formation of the phenol 15 was observed
(Scheme 8).
Scheme 8. With D2O 16 forms 15.
Scheme 10. Generation of the oxepine 24 and reaction with
N-phenyltriazolinedione.
Why is phenol 15 and not the “normal” phenol 14
(coresponding to 2) formed? The ring-opening of the
arene oxides 6 to the phenols 2 proceeds via Wheland
À
intermediates, which can aromatise by C C bond was confirmed by the spectroscopic data, 5.55 ppm for
cleavage if a stabilised cation can be eliminated. Simi- the isolated olefinic proton, 6.24 and 6.34 ppm for the
À
lar C C bond cleavages have been observed previous- other two vinylic protons with a coupling constant of
ly for the elimination of furyl cations.[3c] For 16 this only 7.5 Hz and, most convincingly, no alkyl 13C sig-
means that 19 preferentially fragments to the stabi- nals like the arene oxides discussed above but only
lised cation 22 and the phenol 15 (Sheme 9)
olefinic 13C methine signals between 117.05 and
Synthetically, this is quite useful. If water is present 132.39 ppm (in the arene oxides the epoxide methine
from the beginning of the gold-catalysis, as shown in signal occurred at 66.1 ppm). In 24 the hydrogen
Scheme 4, 13 is formed by deprotection. If no water is atoms of the methylene groups are homotopic and do
present, the oxepine 18 is slowly formed from the ini- not show a geminal coupling. As expected, the other
tial product, the arene oxide 16. If water is added to valence tautomer is still present in low concentration.
16, the constitutional isomer of the normal phenols of When N-phenyltriazolindione was added, the Diels–
type 2, the phenol 15, is formed. So here the acetyl-di- Alder adduct 26 was obtained from the equilibrium
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126 MHz): d=23.34 (q), 65.05 (t, 2C), 103.86 (d), 109.05 (d),
122.46 (s), 152.29 (s), 160.37 (s), 177.89 (d); MS (70 eV): m/z
(%)=182 (21) [M+], 167 (100), 123 (63), 93 (23); anal.
calcd. for C9H10O4 (182.18): C 59.34, H 5.53; found: C 59.47,
H 5.60.
with the arene oxide 25, again as a single diastereo-
1
mer. Adduct 26 shows the typical epoxide H NMR
signal at 3.95 ppm and a 13C resonance of 53.28 ppm
for the epoxy methine group.
Conclusions
4-Methyl-N-[5-(2-methyl-[1,3]dioxolan-2-yl)furan-2-
ylmethyl]-N-prop-2-ynylbenzen-sulfonamide (12)
The in situ formation of arene oxides is not always de-
pendent on a specific ligand system; with the ketal
substrate 12 only the arene oxide intermediate is
formed, even with the simple AuCl3 catalyst. Al-
though the sensitive arene oxide intermediates cannot
be isolated, these intermediates can selectively be
converted to different products. The outcome depends
on the reaction conditions, here a stable oxepine or a
phenol with a specific substituion pattern were pro-
duced.
Substrate 11 (301 mg, 1.65 mmol), propargylamine (182 mg,
3.31 mmol, 2 equivs.) and MgSO4 (1.00 g) in dichlorome-
thane (6 mL) were stirred overnight. After filtration the sol-
vent was removed under vacuum, the residue dissolved in
methanol (15 mL) and NaBH4 (62.5 mg, 1.65 mmol,
1 equiv.) were added. After 2 h water (20 mL) was added
and it was extracted with ether (3”30 mL), dried over
MgSO4, filtered and the solvent evaporated under vacuum.
To the residue tosyl chloride (285 mg, 1.49 mmol, 0.9 equiv.)
and triethylamine (150 mg, 1.49 mmol, 0.9 equiv.) in di-
chloromethane (10 mL) was added. After two days the mix-
ture was hydrolysed with water (20 mL), extracted with di-
chloromethane (3”30 mL), dried over MgSO4, filtered and
the solvent removed under vacuum. Column chromatogra-
phy on silica gel furnished 12 as a colourless solid; yield:
403 mg (72%); Rf (petrol ether:ethyl acetate:dichlorome-
thane, 10:1:2)=0.12; mp 69–708C; IR (KBr): n=3231, 3098,
2972, 2875, 2082, 1678, 1588, 1417, 1340, 1250, 1150, 1075,
With the specific pre-catalyst 7 the aryl-substituted
substrate 23 yields the oxepine 24 and not an arene
oxide.
Experimental Section
1
1021, 998, 876, 785, 640 cmÀ1; H NMR (CDCl3, 500 MHz):
General Remarks
d=1.64 (s, 3H), 2.05 (t, J=2.5 Hz, 1H), 2.40 (s, 3H), 3.94–
4.02 (m, 6H), 4.40 (s, 2H), 6.19 (d, J=3.2 Hz, 1H), 6.20 (d,
J=3.2 Hz, 1H), 7.27 (d, J=8.2 Hz, 2H), 7.71 (d, J=8.2 Hz,
2H); 13C NMR (CDCl3, 62.9 MHz): d=21.53 (q), 24.07 (q),
36.32 (t), 42.92 (t), 65.11 (t, 2C), 73.89 (d), 76.51 (s), 104.40
(s), 107.28 (d), 110.13 (d), 127.72 (d, 2C), 129.51 (d, 2C),
135.97 (s), 143.62 (s), 148.59 (s), 154.94 (s); MS (70 eV): m/z
(%)=375 (16) [M+], 360 (55), 220 (100), 204 (60), 192 (20),
176 (47), 91 (19); anal. calcd. for C19H21NO5S (375.45): C
60.78, H 5.64, N 3.73; found: C 60.83, H 5.69, N 3.65.
Evaporation of a solution of 12 in dichloromethane/ether
delivered single crystals suitable for the crystal structure in-
vestigation.
The multiplicities were assigned to the 13C NMR data via a
combination of DEPT 135 and DEPT 90 spectra and are de-
fined as follows: s (quarternary C), d (CH), t (CH2), q
(CH3).
5-(2-Methyl-[1,3]dioxolan-2-yl)furan-2-carbaldehyde
(11)
To 10[11] (2.90 g, 18.8 mmol) in absolute THF(60 mL) under
an atmosphere of nitrogen at À758C n-BuLi (1.6 mol/L n-
BuLi in hexane, 11.7 mL, 1.00 equiv.) was added. After 3 h
DMF(15 mL, large excess) was added, the reaction mixture
was warmed to room temperature over night, hydrolysed
with ice/water and then neutralised with 6 N HCl. After
three extractions with ether (80 mL each) the combined or-
ganic phases dried over MgSO4 filtered, the solvent evapo-
rated and the residue purified by column chromatography
on silica gel. Thus the known 2-acetylfurfural[11c,12] (420 mg,
16%) and the new 11 (680 mg, 20%) were obtained.
On account of these problems, the reaction was repeated
with 3.00 g (19.5 mmol) of 10 and during the work-up no
HCl was used. This led to 11 in a much higher yield (2.66 g,
75%). From diethyl ether single crystals of 11 for the X-ray
crystal structure investigation were obtained.
Gold-Catalyzed Reaction of 12 in the Presence of
Water
Substrate 12 (101 mg, 269 mmol) was dissolved in 0.5 mL
CD3CN in an NMR tube and D2O (0.2 mL) were added.
Then at room temperature a stock solution of AuCl3 (10
wt% in CD3CN, 40.8 mg, equivalent to 4.08 mg AuCl3, 13.5
1
mmol) was added. The reaction was monitored by H NMR
spectroscopy. In situ NMR showed quantitative and selective
deprotection within 20 min. After that the solvent was re-
moved and the residue was purified by column chromatog-
raphy on silica gel to afford N-(5-acetylfuran-2-ylmethyl)-4-
methyl-N-prop-2-ynylbenzensulfonamide (13) as a yellow
solid; yield: 78 mg (88%); Rf (petrol ether:ethyl acetate,
2:1)=0.25; mp 72–748C; IR (film): n=3296, 3113, 1650,
1511, 1344, 1304, 1257, 1217, 1157, 1092, 1051, 980, 922, 873,
2-Acetylfurfural: 1H NMR (CD3CN, 300 MHz): d=2.52
(s, 3H), 7.30 (d, J=3.8 Hz, 1H), 7.42 (d, J=3.8 Hz, 1H),
9.75 (s, 1H). C7H6O3 (138.12).
11: Rf (petrol ether:ethyl acetate, 2:1)=0.29; column:
petrol ether/ethyl acetate, 3:1; mp 34–368C; IR (film): n=
3103, 2904, 1666, 1512, 1422, 1353, 1292, 1207, 1102, 1021,
1
817, 736 cmÀ1; H NMR (CDCl3, 300 MHz): d=2.10 (t, J=
1
982, 931, 824, 730 cmÀ1; H NMR (CD3CN, 300 MHz): d=
2.5 Hz, 1H), 2.39 (s, 3H), 2.41 (s, 3H), 4.08 (d, J=2.5 Hz,
2H), 4.49 (s, 2H), 6.44 (d, J=3.5 Hz, 1H), 7.08 (d, J=
3.5 Hz, 1H), 7.29 (d, J=8.3 Hz, 2H), 7.72 (d, J=8.3 Hz,
1.70 (s, 3H), 3.93–4.08 (m, 4H), 6.61 (d, J=3.4 Hz, 1H),
7.31 (d, J=3.4 Hz, 1H), 9.58 (s, 1H); 13C NMR (CD3CN,
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A. Stephen K. Hashmi et al.
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2H); 13C NMR (CDCl3, 75.5 MHz): d=21.61 (q), 25.98 (q),
37.02 (t), 43.30 (t), 74.49 (d), 76.17 (s), 111.85 (d), 118.04
(d), 127.72 (d, 2C), 129.72 (d, 2C), 135.66 (s), 144.07 (s),
22.59 (q), 55.64 (t), 55.79 (t), 64.45 (t, 2C), 105.20 (s), 107.45
(d), 112.66 (d), 127.21 (d, 2C), 129.60 (d, 2C), 132.77 (s),
132.85 (d), 133.06 (s), 138.07 (s), 143.90 (s), 149.32 (s); MS
152.80 (s), 153.85 (s), 186.61 (s); MS (FAB positive ion, (EI in CI-volume): m/z (%)=375 (12) [M+], 288 (22), 220
matrix: 3-nitrobenzyl alcohol): m/z (%)=332 (100)
A
(15), 134 (100), 91 (38); HR-MS (EI positive ion in CI
221 (16), 123 (40), 91 (12); anal. calcd. for C17H17NO4S
(331.39): C 61.61, H 5.17, N 4.23; found: C 60.85, H 5.15, N
4.12; HR-MS (FAB positive ion, matrix: 3-nitrobenzyl acko-
hol): m/z=332.0950, calcd. for C17H17NO4S+H+: 332.0957.
volume): m/z=375.1124, calcd. for C19H21NO5S: 375.1140.
5,7,8,9-Tetrahydro-13-(2-methyl-[1,3]dioxolan-2-yl)-8-
[(4-methylphenyl)sulfonyl]-2-phenyl-5,9a-endo-
oxirano-1H,9aH-pyrrolo
A
G
N
a]pyridazine-1,3(2H)-dione (21)
Gold-Catalyzed Conversion of 12 with AuCl3 in
Absolute Solvent
The previous reaction was repeated on the same scale and
when 16 had formed, at room temperature small portions of
4-phenyl-1,2,4-triazoline-3,5-dion were added until no decol-
ourisation was observed any more. In all 26.2 mg
(150 mmol) of the trapping reagent were needed, decolouri-
sation took only seconds. The solvent was removed and the
residue was purified by column chromatography on silica
gel. Thus 21 were obtained as a colourless solid; yield
49.2 mg (33% over both steps). Rf (PE:EE, 1:1)=0.28; mp
99–1018C; IR (film): n=1770, 1707, 1599, 1494, 1400, 1341,
Substrate 12 (101 mg, 269 mmol) was dissolved in 0.5 mL
CD3CN in an NMR tube and at room temperature a stock
solution of AuCl3 in CD3CN (10 wt%, 40.8 mg, equivalent
to 4.08 mg AuCl3, 13.5 mmol) was added. The reaction was
1
monitored by H NMR spectroscopy:
Initially the cleavage of the ketal group furnished a small
amount of 13 and small peaks of 15 became visible. After
10 min this came to an end and the formation of the arene
oxide 16 was observed. Most of the conversion took place in
the first 30 min, but then the reaction became very slow and
even after 90 min there were still signals of the starting ma-
terial visible. The solvent was removed under vacuum and
the residue was purified by column chromatography. Under
these work-up conditions 16 isomerized to 18. The Rf values
are quite similar, thus a complete separation was a signifi-
cant problem. In particular, 16 was always contaminated
with 15 and 18, a clear evidence for the latter two com-
pounds being formed from 16 on the column. Product 18
1230, 1152, 1103, 950, 881, 810, 762 cmÀ1; H NMR (CDCl3,
1
500 MHz): d=1.43 (s, 3H), 2.43 (s, 3H), 3.61 (s, 1H), 3.75
(d, J=7.5 Hz, 1H), 3.89 (dd, J=14.7 Hz, 2.5 Hz, 1H), 3.94
(m, 5H), 4.89 (d, J=11.7 Hz, 1H), 5.38 (d, J=6.1 Hz, 1H),
6.05 (dt, J=6.1 Hz, 2.1 Hz, 1H), 7.33–7.38 (m, 5H), 7.41–
7.45 (m, 2H), 7.76 (d, J=8.4 Hz, 1H, 2H); 13C NMR
(CDCl3, 126 MHz): d=21.69 (q), 22.00 (q), 48.52 (d), 48.67
(t), 51.21 (t), 54.58 (d), 56.52 (s), 65.62 (t), 66.39 (t), 70.44
(s), 107.01 (s), 116.56 (d), 125.61 (d, 2C), 128.22 (d, 2C),
128.52 (d), 129.16 (d, 2C), 129.98 (d, 2C), 131.18 (s), 132.61
(s), 138.96 (s), 144.44 (s), 154.05 (s), 154.18 (s). MS (FAB
positive ion, matrix: 3-nitrobenzyl alcohol): m/z (%)=551
(100) [MH+], 374 (34); HR-MS (FAB positive ion, matrix:
1
cannot be detected in the H NMR spectra of the crude re-
action mixture.
From the column the following amounts of pure com-
pounds could be obtained in addition to some fractions
which contained a mixture of two of the products: 8 mg
(9%) of 13 as a yellow solid, 18 mg (18%) of 18 as a colour-
less solid, and 5 mg (6%) of 15 as a colourless solid. Also,
22 mg of 16 as a colourless solid were obtained, but it con-
tained impurities of 15 and 18. Single crystals for the crystal
structure analysis of 18 were obtained from acetonitrile.
2-(4-Toluenesulfonyl)-2,3-dihydro-1H-isoindol-5-ol (15):[3a]
1H NMR (CDCl3, 300 MHz): d=2.40 (s, 3H), 4.53 (m, 2H),
4.55 (m, 2H), 5.10 (s, 1H, OH), 6.63 (d, J=2.3 Hz, 1H),
6.70 (dd, J=8.3 Hz, 2.3 Hz, 1H), 7.00 (d, J=8.3 Hz, 1H),
7.31 (d, J=8.3 Hz, 2H), 7.75 (d, J=8.3 Hz, 2H).
1a-(2-Methyl-[1,3]dioxolan-2-yl)-5-(toluen-4-sulfonyl)-
4,5,6,6b-tetrahydro-1aH-1-oxa-5-aza-cyclopropa[e]indene
(16): Rf (petrol ether:ethyl acetate:dichloromethane,
10:2:3)=0.20; 1H NMR (CD3CN, 500 MHz): d=1.36 (s,
3H), 2.43 (s, 3H), 3.86–3.94 (m, 4H), 4.10 (s, 1H), 4.25 (t,
J*=4.3 Hz, 2H), 4.58 (t, J*=4.3 Hz, 2H), 6.30 (d, J=
9.8 Hz, 1H), 6.47 (d, J=9.8 Hz, 1H), 7.42 (d, J=8.2 Hz,
2H), 7.74 (d, J=8.2 Hz, 2H).
3-nitrobenzyl
alcohol):
m/z=551.1598,
calcd.
for
C27H26N4O7S+H+: 551.1600; anal. calcd. for C27H26N4O7S
(550.58): C 58.90, H 4.76, N 10.18; found: C 57.62, H 4.92, N
9.38.
From a mixture of petroleum ether, dichloromethane and
diethyl ether suitable crystals for the X-ray crystal structure
analysis could be obtained. 21:
Reaction of 16 with D2O
To 12 (101 mg, 269 mmol) in 0.5 mL CD3CN in an NMR
tube, a stock solution of AuCl3 in CD3CN (10 wt%, 40.8 mg,
corresponiding to 4.08 mg AuCl3, 13.5 mmol, 5 mol%) was
added at room temperature. The reaction was monitored by
1H NMR. After the conversion to 16 had stopped, D2O
1
(2 mL) was added. H NMR showed that 16 was converted
to 15 and the remaining starting material 12 was deprotect-
ed to 13. Water (10 mL) was added, after three extractions
with dichloromethane (10 mL each) the combined extracts
were dried over MgSO4, filtered and the solvent was re-
moved under vacuum. Column chromatography on silica gel
furnished 13 (12 mg, 13%) and 15 (49 mg, 63%).
5-(2-Methyl-[1,3]dioxolan-2-yl)-2-(toluen-4-sulfonyl)-2,3-
dihydro-1H-oxepino[4,5-c]pyrrole (18): Rf (petrol ether:eth-
E
yl acetate:dichloromethane, 10:2:3)=0.20; mp 92–938C; IR
1
(film): n=2359, 2184, 1642, 1342, 1163, 1103 cmÀ1; H NMR
6-(4-Bromphenyl)-1H,3H-furo[3,4-c]oxepine (24)
A
(CD3CN, 300 MHz): d=1.46 (s, 3H), 2.44 (s, 3H), 3.86–3.94
(m, 4H), 4.17 (s, 4H), 5.57 (d, J=5.0 Hz, 1H), 5.78 (d, J=
5.0 Hz, 1H), 5.87 (s, 1H), 7.43 (d, J=8.3 Hz, 2H), 7.73 (d,
J=8.3 Hz, 2H); 13C NMR (CDCl3, 300 MHz): d=20.19 (q),
Substrate 23 (100 mg, 343 mmol) was dissolved in absolute
chloroform (1.5 mL) and catalyst 7 (6.4 mg, 17 mmol) was
added. After 10 min a layer of petroleum ether was added
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Gold Catalysis: Oxepines from g-Alkynylfurans
FULL PAPERS
and the solution was stored at À288C. After 5 days a brown-
ish precipitate containing yellow-brown spherical particles
had formed. The solvent was removed with a pipette and
the spherical particles selected with a tweezers. Thus 24,
which slowly decomposed to the corresponding phenol, was
obtained; yield: 37 mg (37%). IR (film): n=3075, 2878,
2822, 1711, 1606, 1476, 1428, 1354, 1269, 1221, 1164, 1116,
Chem. Lett. 1987, 16, 405–408; b) G. J. Hutchings, J.
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4137; Angew. Chem. Int. Ed. 2005, 44, 4066–4069.
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Dyker, Angew. Chem. 2000, 112, 4407–4409; Angew
Chem. Int. Ed. 2000, 39, 4237–4239; b) A. S. K.
Hashmi, Gold Bull. 2003, 36, 3–9; c) A. S. K. Hashmi,
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e) A. S. K. Hashmi, Angew. Chem. 2005, 117, 7150–
7154; Angew. Chem. Int. Ed. 2005, 44, 6990–6993;
f) A. S. K. Hashmi, G. Hutchings, Angew. Chem. 2006,
118, 8064–8105; Angew. Chem. Int. Ed. 2006, 45, 7896–
7836.
1032, 831, 770, 700, 663, 606 cmÀ1
;
1H NMR (CDCl3,
500 MHz): d=4.63 (s, 2H), 4.65 (s, 2H), 5.33 (s, 1H), 6.24
(d, J=7.5 Hz, 1H), 6.34 (d, J=7.5 Hz, 1H), 7.41–7.49 (m,
4H); 13C NMR (CDCl3, 75.5 MHz): d=70.25 (t), 72.94 (t),
112.14 (s), 117.05 (d), 121.50 (d), 122.54 (s), 125.53 (s),
127.26 (d, 2 C), 131.81 (d, 2 C), 132.39 (d), 135.51 (s), 140.13
(s). C14H11O2Br (291.14).
[3] a) A. S. K. Hashmi, T. M. Frost, J. W. Bats, J. Am.
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Reaction of the Intermediate Oxepine Obtained from
23 with 4-Phenyl-1,2,4-triazoline-3,5-dione
To 23 (100 mg, 343 mmol) in absolute chloroform (5 mL) the
catalyst 7 (6.5 mg, 17.2 mmol, 5 mol%) was added. After
1
90 min at room temperature, when in the H NMR only sig-
nals of the oxepine 24 were visible, the reaction mixture was
cooled to 08C. Then 4-phenyl-1,2,4-triazoline-3,5-dione
(60.1 mg, 343 mmol) was added. The initially red solution
quickly turned light brown. It was stored atÀ288C over-
night. Column chromatograpy on silica gel (petroleum
ether:acetone:dichloromethane, 10:1:1) furnished 26 as a
yellow solid; yield: 75 mg (47%). Rf (petrol ether:aceton:di-
chloromethane, 10:1:1)=0.08; mp 78–808C; IR (film): n=
2923, 2848, 1771, 1711, 1593, 1495, 1399, 1244, 1140, 1054,
´
M. Rudolph, E. Kurpejovic, Angew. Chem. 2004, 116,
6707–6709; Angew. Chem. Int. Ed. 2004, 43, 6545–
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E. Kurpejovic, W. Frey, J. W. Bats, Adv. Synth. Catal.
1009, 908, 850, 823, 763, 721, 688, 649 cmÀ1 1H NMR
;
2006, 348, 709–713; i) A. S. K. Hashmi, P. Haufe, C.
Schmid, A. Rivas Nass, W. Frey, Chem. Eur. J. 2006, 12,
5376–5382; j) A. S. K. Hashmi, R. SalathØ, W. Frey,
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M. Wçlfle, F. Ata, M. Hamzic, R. SalathØ, W. Frey,
Adv. Synth. Catal. 2006, 348, 2501–2508; l) A. S. K.
(CDCl3, 300 MHz): d=3.85 (s, 1H), 4.35 (ddd, J=14.3 Hz,
2.6 Hz, 0.7 Hz, 1H), 4.59 (ddd, J=14.3 Hz, 1.8 Hz, 0.7 Hz,
1H), 5.28 (d, J=11.1 Hz, 1H), 5.28 (d, J=11.1 Hz, 1H),
5.58 (d, J=5.9 Hz, 1H), 6.15 (dt*, J=5.9 Hz, J=2.1 Hz,
1H), 7.53–7.38 (m, 7H), 7.64–7.59 (m, 2H). (* expected:
3
4
4
ddd, J=5.9 Hz, J=2.6 Hz, J=1.8 Hz); 13C NMR (CDCl3,
62.9 MHz): d=53.28 (d), 55.64 (s), 59.28 (d), 68.26 (t), 70.48
(t), 73.95 (s), 114.45 (d), 123.36 (s), 127.37 (d, 2 C), 129.07
(d, 2 C), 129.65 (d), 130.06 (d, 2 C), 132.30 (s), 132.83 (d, 2
C), 134.96 (s), 143.92 (s), 155.64 (s), 156.17 (s); MS (EI
70 eV): m/z (%)=467 (1) [81BrÀM+], 465 (1) [79BrÀM+],
322 (9), 292 (60), 290 (63), 263 (41), 261 (39), 183 (36) , 182
(39), 181 (36), 119 (100); HR-MS (EI, 70 eV): m/z=
465.0324, calcd. for C22H16BrN3O4: 465.0324.
´
Hashmi, J. P. Weyrauch, E. Kurpejovic, T. M. Frost, B.
Miehlich, W. Frey, J. W. Bats, Chem. Eur. J. 2006, 12,
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209; Angew. Chem. Int. Ed. 2006, 45, 200–203; L.
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348, 2271–2296.
[5] a) B. Martꢁn-Matute, D. J. Cardenas, A. M. Echavarren,
Angew. Chem. 2001, 113, 4890–4893; Angew. Chem.
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Nevado, D. J. Cꢂrdenas, A. M. Echavarren, J. Am.
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Chem. 2004, 76, 453–463.
[6] CCDC 631909 (11), 631911 (12), 631912 (18) and
631913 (21) contain the supplementary crystallographic
data for this paper. These data can be obtained online
free of charge (or from the Cambridge Crystallographic
Data Centre, 12, Union Road, Cambridge CB2 1EZ,
UK; fax: (+44) 1223–336–033; or mailto:depo-
sit@ccdc.cam.ac.uk).
As a side-product the known aldehyde formed by the hy-
drolysis of the intermediate gold carbenoid species[3k]
(4.1 mg, 4%) was isolated.
Acknowledgements
This work was supported by the Fonds der Chemischen In-
dustrie and by the Deutsche Forschungsgemeinschaft (HA
1932/10–1).
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Adv. Synth. Catal. 2007, 349, 1743 – 1750