A gold(I)-catalyzed intramolecular reaction of propargylic/homopropargylic alcohols with oxirane

Article abstract of DOI:10.1002/chem.200701954

The gold(I)-catalyzed cycloisomerization of epoxy alkynes in the presence of a nucleophile is an efficient protocol to provide ketal skeletons with high stereoselectivity. An intramolecular reaction of propargylic/homopropargylic alcohols with oxirane to produce ketal/spiroketals in moderate yields under mild conditions has been reported. Moreover, the mechanism of this kind of reaction has been discussed on the basis of a series of control and ¹⁸O tracer experiments.

Full text of DOI:10.1002/chem.200701954

FULL PAPER
DOI: 10.1002/chem.200701954
A Gold(I)-Catalyzed Intramolecular Reaction of Propargylic/
Homopropargylic Alcohols with Oxirane
Lun-Zhi Dai and Min Shi*[a]
Abstract: The gold(I)-catalyzed cycloisomerization of epoxy alkynes in the pres-
ence of a nucleophile is an efficient protocol to provide ketal skeletons with high
stereoselectivity. An intramolecular reaction of propargylic/homopropargylic alco-
hols with oxirane to produce ketal/spiroketals in moderate yields under mild con-
ditions has been reported. Moreover, the mechanism of this kind of reaction has
been discussed on the basis of a series of control and 18O tracer experiments.
Keywords: alcohols · cyclization ·
diastereoselectivity
·
domino
reactions · gold · ketals
Introduction
Ketals[1] are important subunits in a large number of biologi-
cally active natural products. The acid-catalyzed cyclization
of dihydroxy ketones, or equivalents thereof, is one of the
most important strategies in the preparation of ketal-con-
taining molecules.[1g–i,2] Gold salts, known as a type of pow-
erful soft Lewis acid, can readily activate alkynes, allenes,
and olefins toward attacks by a variety of nucleophiles.[3,4]
À
Numerous highly efficient C O bond-forming reactions
Scheme 1. Gold-catalyzed cycloisomerization of epoxy alkynes.
have recently been reported in which alkynes are activated
toward nucleophilic attacks by alcohols,[5] carbonyl com-
pounds,[6] and carboxylic acids.[7]
mediate D. Whereas in path II, selective activation of oxir-
ane of A by a gold salt afforded intermediate E, which was
followed by a nucleophilic ring-opening reaction to form an
opened oxirane intermediate F. An intramolecular attack
toward the alkyne by the newly formed hydroxy group gave
the product H via intermediate G. Interestingly, soon after
our discovery, Liang and co-workers reported the similar
gold-catalyzed transformation of epoxy alkynes.[10]
Our continuous interest in the melt-catalyzed domino cy-
cloisomerization of epoxy alkynes[11] promoted us to investi-
gate further the generality and mechanism of this kind of re-
action. Herein, we report a gold-catalyzed intramolecular
reaction of propargylic/homopropargylic alcohols with oxir-
ane to afford the corresponding ketals and spiroketals in
moderate yield under mild conditions.
Our earlier work on a gold-catalyzed cascade cyclization
reaction of epoxy alkynes to yield ketals provided an effi-
cient alternative to the construction of the C O bond. We
proposed two reaction pathways (Scheme 1): In path I, the
coordination of a cationic gold species to the epoxy alkyne
unit of A gave complex B, in which an intramolecular attack
toward the alkyne by oxirane resulted in an oxonium ion
C.[9] Subsequent ring-opening of the oxonium ion in the
presence of an alcohol produced the product H via inter-
[8]
À
[a] L.-Z. Dai, Prof. Dr. M. Shi
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry
Chinese Academy of Sciences
354 Fenglin Lu, Shanghai 200032 (China)
Fax : (+86)21-6416-6128
E-mail: mshi@mail.sioc.ac.cn
Results and Discussion
Supporting information (detailed experimental procedures, spectro-
scopic, and analytic data of the all new compounds) for this article is
available on the WWW under http://dx.doi.org/10.1002/
anie.200701954.
The routine synthetic sequence for the preparation of start-
ing materials 2 is shown in Scheme 2. The treatment of an
Chem. Eur. J. 2008, 14, 7011 – 7018
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
7011

amount of water into the reaction system did not influence
the yield of 3a (Table 1, entry 9). We also examined the use
of AuCl3 in this reaction to improve the yield of 3a, al-
though the outcome was not rewarding (Table 1, entry 10).
Other Lewis acids, such as BF3·Et2O, did not have any cata-
lytic ability in the reaction (Table 1, entry 11).
This interesting gold(I)-catalyzed reaction could be suc-
cessfully extended to a variety of epoxy propargylic alcohols
with different substituents (Table 2). The reaction proceeded
Scheme 2. Preparation of the epoxy propargylic alcohols. Reagents and
conditions: a) TsCl (0.9 equiv), Et3N (1.0 equiv), CH2Cl2, 08C, RT; b) 3-
bromopropyne (1.5 equiv), K2CO3 (1.5 equiv), acetone, 608C; c) m-
CPBA (2.0 equiv), CH2Cl2, RT, (64%; three steps); d) nBuLi (1.1 equiv),
R1COR2 (1.1 equiv), THF, À788C (50–83%).
Table 2. Scope of the intramolecular reaction of propargylic alcohols
with oxirane.
allylic amine with 4-methylbenzenesulfonyl chloride (TsCl)
and 3-bromopropyne produced the desired 1,6-enyne. Epox-
idation of the 1,6-enyne with 3-chloroperbenzoic acid (m-
CPBA) yielded the alkynyloxirane 1. After treatment of 1
with n-butyllithium in THF, the nucleophilc addition to ke-
tones or aldehydes afforded the corresponding epoxy prop-
argylic alcohols 2 in moderate-to-good yields. With substrate
2a (R1 =R2 =Me) in hand, several combinations of gold(I)
and silver salts were screened (Table 1). The treatment of
Entry Starting material R1 R2
t [h] Product Yield [%][a,b]
1
2
3
4
5
2b
2c
2d
2e
2 f
H
H
H
H
H
C6H5
p-ClC6H4
m-ClC6H4
p-OMeC6H4 21
Et
12
10
30
3b
3c
3d
3e
3 f
50
56
52
12
31
13
18
19
6
7
2g
2h
3g
3h
32
51
Table 1. Efficiency of catalysts for the cycloisomerization of epoxy prop-
argylic alcohol 2a.
Et Et
[a] Yield of the isolated products. [b] Product 3 was obtained as the
E configuration.
smoothly when the R1 moiety was a hydrogen atom and R2
was a phenyl group or an aromatic ring bearing an electron-
withdrawing group (Table 2, entries 1–3). Introducing an
electron-donating group onto the aromatic ring of the R2
group resulted in a remarkable loss of yield (Table 2,
entry 4). When the R2 group was switched to an alkyl group,
the epoxy propargylic alcohol 2 f was converted into the cor-
responding ketal 3 f in 31% yield under identical conditions
(Table 2, entry 5). The use of other epoxy propargylic alco-
hols, such as 2g and 2h, under the standard conditions af-
forded the desired products 3g and 3h in moderate yields
(Table 2, entries 6 and 7). It should be emphasized that in
all cases ketals 3 were obtained exclusively as the E configu-
ration. However, when the O-tethered epoxy propargylic al-
cohol 2i was subjected to the optimized conditions, only a
mixture of product 3i and 3i’ was obtained in low yield
(Scheme 3).
Entry
Catalyst [3 mol%]
[AuClPPh3]/AgSbF6
[AuClPPh3]/AgOTf
[AuClPPh3]/AgO2CCF3
[Au2Cl2{(R)-binap}]/AgOTf
[AuClPMe3]/AgOTf
[AuCl{P(a-furyl)3}]/AgOTf
[AuClPPh3]/AgOTf
[AuClPPh3]/AgOTf
[AuClPPh3]/AgOTf
AuCl3
BF3·Et2O (30 mol%)
t [h]
Yield [%][a]
1
2
3
4
5
G
12
12
72
23
24
28
10
12
20
10
10
29
51
trace
43
14
trace
46
46
51
trace
0
ACHTREUNG
G
ACHTREUNG
T
6
G
G
7[b]
8[c]
9[d]
10
11
ACHTREUNG
N
G
[a] Yield of the isolated product. [b] DCE: 1.0 mL. [c] DCE: 3.0 mL.
[d] Added H2O: 1.0 equiv. binap=2,2’-bis(diphenylphosphino)-1,1’-
binaphthyl.
2a with 3 mol% of [AuClPPh3]/AgOTf (OTf=trifluoro-
On the basis of the above results, two tentative mecha-
nisms for the observed gold-catalyzed cycloisomerization of
epoxy propargylic alcohols to produce ketals were proposed.
A
temperature for 12 h gave the best result, thus providing the
corresponding ketal product
3a in 51% yield (Table 1,
entry 2 compared to entries 1,
3–6). Variation in the concen-
tration of the solution is possi-
ble without substantial loss of
yield (Table 1, entries 7 and 8).
Adding
a
stoichiometric
Scheme 3. Gold-catalyzed isomerization of 2i. DCE=dichloroethane.
7012
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Chem. Eur. J. 2008, 14, 7011 – 7018

Gold(I)-Catalyzed Cycloisomerization
FULL PAPER
According the discovery by
Chung and co-workers,[12] the
epoxy propargylic alcohol 2a
undergoes a rearrangement in
the presence of a cationic gold
complex to give cumulene in-
termediate J via gold-activated
intermediate I. The intermedi-
Scheme 6. A crossover experiment.
ate J could be attacked by water to give intermediate K,
which tautomerizes to intermediate L. Then, a gold-cata-
lyzed intramolecular reaction of the ketone with oxirane
takes place, thus leading to the ketal 3a via intermediate M
(Scheme 4).
The Meyer–Schuster reaction is also a possible rearrange-
ment for the isomerization of I to L (Scheme 5). This pro-
cess involves a 1,3-shift of the hydroxy moiety, followed by
tautomerization of the presumed allenol intermediate K.[13]
Notably, when the reaction of epoxy propargylic alcohol
2j, catalyzed by [AuClPPh3]/AgOTf in DCE at room tem-
perature, was carried out under the standard conditions, to
our disappointment, none of the target product 3j was ob-
tained and 91% of starting material 2i was recovered
(Scheme 6). In addition, according to the mechanism shown
in Scheme 4, a tertiary propargylic alcohol with a hydrogen
atom at the a position to the alkyne unit would be in favor
of isomerization.[12] However, no such isomerization of the
propargylic alcohol to a,b-unsaturated ketone 3j’ was ob-
served either under similar reaction conditions (Scheme 6).
Furthermore, a deuterium-labeling experiment was car-
ried out using [D]-2a (D>99%) as the substrate under the
standard conditions (Scheme 7). None of the deuterium
atoms were lost during the reaction. On the basis of this
result, the existence of intermediate J shown in Scheme 4
can be excluded, and Scheme 5 should be the plausible reac-
tion mechanism.
Scheme 7. A deuterium-labeling experiment
Scheme 5 involves an equilibrium step between intermedi-
ates J1 and J2. If intermediate J1, which was formed by re-
lease of H2O from the propargylic alcohol, returned to inter-
mediate I much faster than its tautomerization to intermedi-
ate J2, intermediate K could not be produced and none of
the a,b-unsaturated ketone L would be obtained. The fol-
lowing 18O-labeling experiment shown in Scheme 8 support-
ed our assumption. When 2j was subjected to the standard
reaction conditions along with
Scheme 4. Proposed mechanism of the gold-catalyzed cycloisomerization
of epoxy propargylic alcohols.
the addition of 5.0 equivalents
of H218O (18O>97.7%) to the
reaction system, 12% of 18O-
labeling product 2j’ was ob-
tained (as determined by
EIMS analysis), presumably as
a result of the existence of two
phenyl groups, the cationic in-
termediate J1-Ph is very stable,
thus rendering the isomeriza-
tion of J1-Ph to J2-Ph to be much
more difficult.[14] Therefore,
the cycloisomerization of 2j
did not take place under iden-
tical conditions. On the basis
of these control and 18O tracer
Scheme 5. Proposed mechanism for the isomerization of I to L.
experiments,
a
gold(I)-cata-
Chem. Eur. J. 2008, 14, 7011 – 7018
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7013

M. Shi and L.-Z. Dai
Scheme 9. A crossover control experiment.
lation/acetal, or spiroacetal formation of unactivated inter-
nal alkynols using a platinum(II) complex and an unusual
cationic gold(I) complex as mild catalysts.[16c] Epoxy homo-
propargylic alcohols 7 were prepared in a similar way to
that shown in Scheme 2, and the synthetic procedures are
given in Scheme 10. To develop the catalytic version, we ex-
Scheme 8. An 18O-labeling experiment.
lyzed Meyer–Schuster rearrangement of propargylic alco-
hols 2 is most likely to be responsible for the formation of
ketals 3.
Mechanistically, this reaction might also proceed in a
tandem sequence involving the first step of the ring-opening
of oxirane. However, recent reports show that most of the
isomerization of propargylic alcohols to ketals could be fin-
ished within four hours[12] and that the ring-opening of oxir-
ane in the presence of water or alcohol catalyzed by gold
needed a longer reaction time.[8] Thus, the mechanism in-
volving the ring-opening of oxirane as the first step could be
excluded according to literature reports. In addition, the re-
action might also involve an oxonium ion, which was
formed by the nucleophilic attack of the oxygen atom in the
epoxide unit on the gold-coordinated alkyne.[15] To test this
hypothesis, the reaction of epoxy alkyne 1 in ethanol cata-
lyzed by 3 mol% of [AuClPPh3]/AgOTf was carried out.
However, none of the cyclized product was observed, except
25% of ring-opened product 5 (Scheme 9). Although this
result does not provide direct evidence, the possibility of an
oxonium ion as an intermediate involving the reaction pro-
cess was much lower on the basis of the above control ex-
periment. Therefore, if reconsi-
Scheme 10. Preparation of the epoxy homopropargylic alcohol. Reagents
and conditions: a) nBuLi (1.1 equiv), oxirane (2.0 equiv), BF3·Et2O
(2.0 equiv), THF, À788C (52%); b) m-CPBA (2.0 equiv), CH2Cl2, RT
(45%).
amined the reaction of 7a in the presence of several kinds
of catalysts in ethanol and the results of these experiments
are summarized in Table 3. We found that using 30 mol% of
para-toluene-4-sulfonic acid (p-TsOH) as a co-catalyst with
5 mol% of [AuClPPh3]/AgSbF6 was the best combination
for the reaction at room temperature (208C), thus affording
the desired product 8a in 50% yield (d.r.=24:76) along
with the formation of 9a as the by-product (Table 3, en-
À
tries 1–7). The weakly coordinating anion SbF6 proved to
be particularly well suited to this reaction (Table 3, entries 3,
dering the mechanism shown
Table 3. Optimization of the reaction conditions.
in Scheme 1, the reaction in-
volving the oxonium ion could
be excluded according to the
experimental observations.
We next turned our atten-
tion to the construction of spi-
roketals by using epoxy homo-
propargylic alcohols as the
starting materials in ethanol.
Entry
p-TsOH
[equiv]
AuX/AgY
t [h]
8a
9a
N
yield [%][a]
d.r.[b]
yield [%][a]
1
2
3
0.1
0.2
0.3
0.3
0.5
0.5
1.0
0.3
0.3
0.3
0.3
A
10.5
7
5.4
2
3
8
16.5
6.5
13
12.5
23.5
39
41
50
24
42
21
24
34
44
42
51
48:52
46:54
24:76
10
10
15
15
16
21
18
12
15
13
10
C
Although
many
synthetic
N
methods for the preparation of
spiroketals are known, little at-
tention has been paid to the
approach based on the use of
gold catalysts.[5,16] Recently,
Liu and De Brabander dis-
closed an elegant study on the
room-temperature cycloisome-
rization, tandem hydroalkoxy-
4[c]
5
N
14.5:85.5
31.5:60.5
16.7:83.3
14.5:85.5
38:62
35.5:64.5
31:69
17:83
E
6
N
7[d]
8
G
AHCTREUNG
9
N
10
R
11[e]
E
[a] Yield of the isolated products. [b] Determined by HPLC. [c] Temperature: 608C. [d] The reaction was car-
ried out in CH2Cl2 with the addition of 5.0 equivalents of EtOH. [e] [AuClPPh3]/AgSbF6: 2 mol%.
7014
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Chem. Eur. J. 2008, 14, 7011 – 7018

Gold(I)-Catalyzed Cycloisomerization
FULL PAPER
8, and 9). Moreover, we also found that the yield and diaste-
reoselectivity of 8a decreased if using an electron-rich alkyl-
phosphine as a ligand under otherwise identical conditions
(Table 3, entry 10). The best result was obtained by decreas-
ing the amount of [AuClPPh3]/AgSbF6 to 2 mol%, thus af-
fording the desired product 8a in 51% overall yield along
with 10% yield of by-product 9a under the standard condi-
tions (Table 3, entry 11). Although much effort has been put
into decreasing the amount of by-product 9a obtained, no
satisfactory result could be obtained thus far.
alyzed domino cyclization are shown in Scheme 11. As for
the secondary epoxy homopropargylic alcohol 7b, the corre-
sponding spiroketal 8g was obtained in only 21% yield and
9b was formed as the major product in 46% yield under the
With these optimal results, a wide range of alcohols as the
nucleophile were examined (Table 4). The treatment of 7a
Table 4. The effect of nucleophiles.
Scheme 11. Scope of gold-catalyzed cycloisomerization of epoxy homo-
propargylic alcohols to spiroketals.
Entry ROH
t [h]
8
9a
product yield d.r.[b] yield d.r.[b]
[%][a]
[%][a]
standard conditions. However, the transformation of epoxy
homopropargylic alcohol 7c into the spiroketal 8h indicated
that the ring-opening of oxirane was facilitated when a 1’,2’-
disubstituted epoxide bearing a phenyl group was employed,
thus affording the corresponding spiroketal 8h in 70% yield
as a 11:89 diastereomeric mixture (Scheme 11).
To shed light on the reaction mechanism, we treated the
epoxy homopropargylic alcohol 7a with [AuClPPh3]/AgSbF6
for 1.5 hours in the absence of a Brønsted acid. The cyclic
ketal 10a was obtained in 60% yield under otherwise identi-
cal conditions (Scheme 12). On further prolonging the reac-
tion time, the cyclic ketal 10a was consumed and the spiro-
ketal 8a was slowly formed. This result suggests that the spi-
roketal 8a might be formed via intermediate 10a and p-
TsOH would play an important role in the ring-opening of
oxirane.
Based on the assumption that the tandem process took
place via 2,3-dihydrofuran 10a (see Scheme 12), we pro-
posed a plausible reaction mechanism (Scheme 13). The in-
termediate O, obtained through the pathway reported previ-
ously,[8] was transformed into ketal 10a upon nucleophilic
attack by an alcohol. The subsequent ring-opening of oxir-
ane catalyzed by p-TsOH or a cationic gold catalyst provid-
ed intermediate P, followed by an intramolecular ketal-ex-
change that resulted in the formation of intermediate 8a-1
or 8a-2 through intermediate Q or R. According to the pre-
vious reports, it was clear that there should be a heavy pref-
1
2
3
4
5
6
MeOH
CH2=CHCH2OH 47
24
8b
8c
8d
8e
44
52
39
32
46[c]
0
12:88 10
–
–
13:87 trace
33:67 35
35:65 23
nPrOH
iPrOH
nBuOH
tBuOH
tBuOH
tBuCH2OH
41
53
24.5 8 f
65
29
76
3:97
<1:99
–
15:85
5.6:94.4
14:86
–
–
–
–
trace
35
69
–
–
–
7[d]
8
0
0
17
[a] Yields of the isolated products. [b] Diastereoselectivities were deter-
mined by HPLC. [c] The d.r. was not determined. [d] The amount of
H2O added was 2.0 equivalents.
with methanol resulted in the formation of spiroketal 8b in
44% yield and 9a in 10% yield (Table 4, entry 1). Other al-
cohols, such as prop-2-en-1-ol, propan-1-ol, propan-2-ol, and
butan-1-ol, were also active to the reaction to give the corre-
sponding spiroketals 8 in moderate yields (Table 4, en-
tries 2–5). It is noteworthy that the steric bulkiness of the
employed alcohols had a great influence on the diastereose-
lectivity of 8. When sterically bulky nucleophiles were uti-
lized, the achieved diastereoselectivities of 8 were relatively
lower (Table 4, entries 3 and 4). However, when 2-methyl-
propan-2-ol or 2,2-dimethylpropan-1-ol were used as the nu-
cleophile, spiroketal 9a (by-product) was obtained in low
yield without the formation of the desired spiroketal 8,
probably because the sterically bulky tert-butyl group might
block the nucleophilic attack of the alcohols (Table 4, en-
tries 6–8). When 2.0 equivalents of water were added to the
reaction mixture of 7a with 2-
methylpropan-2-ol, spiroketal
9a could be exclusively ob-
tained in 69% yield and the
diastereomeric
ratio
was
5.6:94.4 (Table 4, entry 7).
Further extensions of this
gold and Brønsted acid co-cat-
Scheme 12. Substrate 7a was subjected to the optimized conditions in the absence of p-TsOH
Chem. Eur. J. 2008, 14, 7011 – 7018
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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7015

M. Shi and L.-Z. Dai
In conclusion, we have de-
veloped a novel gold-catalyzed
cycloisomerization of epoxy
propargylic/homopropargylic
alcohols to ketals/spiroketals
under mild conditions.
mechanism probably involving
Meyer–Schuster rearrange-
A
a
ment of propargylic alcohols
has been proposed in the gold-
catalyzed formation of ketals.
In addition, the mechanism of
the
cycloisomerization
of
epoxy alkyne 1 catalyzed by
gold to give the corresponding
Scheme 13. Proposed mechanism for a tandem process via 2,3-dihydrofuran 10a.
ketal has been elucidated by
exclusive involvement of an
À
erence for a C O bond at the 2-position of a tetrahydrofur-
oxonium ion intermediate. Moreover, we have demonstrated
that the transformation of the epoxy homopropargylic alco-
hol 7a to 8a proceeded through the key intermediate 10a[20]
and that the ring-opening reaction of oxirane was probably
the rate-determining step. Further work directed at elucida-
tion of the detailed mechanisms of this process and the ap-
plication of it to the synthesis of ketal/spiroketal-containing
natural products is currently in progress.
an ring to reside in an axial orientation because of the
anomeric effect.[17] That is to say, that 8a-2 should be the
main diastereoisomer. Moreover, spiroisomerization be-
tween 8a-1 and 8a-2 probably can proceed via intermediate
S. An energetically favorable perpendicular attack by an al-
cohol could occur from either of two directions, for example,
path a or b. The nucleophilic attack through path b would
À
lead to a chair conformation with the newly formed C O
bond axial to the ring. Therefore, path b should be favorable
during this spiroisomerization.[18]
A mixture of diastereoisomers (8a-1/8a-2=28:72) was
placed in a solution of ethanol and the presence of 30 mol%
of p-TsOH to obtain some details about the spiroisomeriza-
tion between 8a-1 and 8a-2 in the presence of a Brønsted
acid.[19] The diastereomeric ratio decreased to 13.8:86.2 (8a-
1/8a-2) after 8 hours (Figure 1). Further prolonging the reac-
Experimental Section
General: Melting points were obtained with a Yanagimoto micro melt-
ing-point apparatus and are uncorrected. 1H NMR spectra in solution
were recorded on a Bruker AM-300 spectrometer in CDCl3 with tetrame-
thylsilane (TMS) as the internal standard; the J values are given in Hertz
(Hz). Mass spectra were recorded with a HP-5989 instrument. All of the
compounds reported herein gave satisfactory microanalyses with a Carlo-
Erba 1106 analyzer or HRMS analytic data. Commercially obtained re-
agents were used without further purification. All of these reactions were
monitored by TLC with plates coated with GF254 silica gel (Huanghai).
Flash column chromatography was carried out using 300—400-mesh
silica gel at medium pressure.
Typical procedure for the preparation of ketals from epoxy propargylic
alcohols in the presence of [AuClPPh3]/AgOTf in DCE at room temper-
ature: [AuClPPh3] (0.009 mmol) and AgOTf (0.009 mmol) were added to
a
solution of N-(4-hydroxy-4-methyl-pent-2-ynyl)-4-methyl-N-oxiranyl-
methylbenzenesulfonamide (2a; 96.9 mg, 0.3 mmol) in DCE (3.0 mL) at
room temperature. The reaction mixture was stirred for 12 h then diluted
with CH2Cl2, evaporated under reduced pressure, and purified by flash
column chromatography on silica gel using EtOAc/PE (1:6) as the eluent.
Compound 3a was isolated in 51% yield as a colorless solid, which was
suitable for analytical purposes.
Figure 1. Spiroisomerization of 8a in the presence of p-TsOH.
5-(2-Methylpropenyl)-3-(toluene-4-sulfonyl)-6,8-dioxa-3-aza-bicyclo-
AHCTREUNG
tion time did not affect the diastereoselectivity. Although
we proved in Scheme 8 that the transformation of epoxy ho-
mopropargylic alcohol 7a to 10a was very fast and the intra-
molecular ketal-exchange could be completed within a short
time,[8] the diastereomeric ratio of 8a was only 17:83 even
after 23.5 hours in the presence of p-TsOH and gold cata-
lysts (Table 3, entry 11), thus indicating that the ring-open-
ing of oxirane was probably the rate-determining step.
1
1679, 1597, 1453, 1348, 1167, 1101, 980 cmÀ1; H NMR (CDCl3, 300 MHz,
TMS): d=1.75 (d, J=0.9 Hz, 3H), 1.83 (s, 3H), 2.44 (s, 3H), 2.55 (d, J=
11.4 Hz, 1H), 2.81 (d, J=11.4 Hz, 1H), 3.52 (d, J=11.4 Hz, 1H), 3.60 (d,
J=11.4 Hz, 1H), 3.88 (t, J=6.0 Hz, 1H), 4.11 (d, J=6.9 Hz, 1H), 4.59–
4.60 (m, 1H), 5.26 (s, 1H), 7.33 (d, J=8.0 Hz, 2H), 7.65 ppm (d, J=
8.0 Hz, 2H); 13C NMR (CDCl3, 75 MHz, TMS): d=19.4, 21.5, 26.5, 47.8,
52.2, 67.6, 72.1, 104.1, 119.7, 127.5, 129.7, 132.9, 141.8, 143.8 ppm; MS
(EI): m/z (%): 83 [M+À240, 28.9], 168 [M+À155, 100.0]; HRMS: m/z:
calcd for C16H21NO4S: 323.1191; found: 323.1192.
7016
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Chem. Eur. J. 2008, 14, 7011 – 7018

Gold(I)-Catalyzed Cycloisomerization
FULL PAPER
Typical procedure for the preparation of ketals from epoxy homopropar-
gylic alcohols in the presence of [AuClPPh3]/AgSbF6 and p-TsOH in eth-
anol at room temperature: p-TsOH (0.09 mmol), [AuClPPh3]
(0.006 mmol), and AgSbF6 (0.006 mmol) were added to a solution of N-
(5-hydroxy-pent-2-ynyl)-4-methyl-N-oxiranylmethylbenzenesulfonamide
(7a; 92.7 mg, 0.3 mmol) in ethanol (3 mL) at room temperature. The re-
action mixture was stirred for 23.5 h, diluted with CH2Cl2, evaporated
under reduced pressure, and purified by flash column chromatography on
silica gel using EtOAc/petroleum ether (1:6) as the eluent. Compound 8a
was isolated in 51% yield as a colorless oil, which was suitable for analyt-
ical purposes.
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7-Ethoxymethyl-9-(toluene-4-sulfonyl)-1,6-dioxa-9-aza-spiro
C
;
1H NMR (CDCl3, 300 MHz, TMS) (two diastereoisomers): d=1.16 (and
1.17) (t, J=6.9 Hz, 3H), 1.68–1.75 (m, 1H), 1.86–2.08 (m, 3H), 2.14–2.31
(m, 1H), 2.44 (s, 3H), 2.47 (d, J=11.4 Hz, 1H), 3.35–3.70 (m, 6H), 3.88–
4.24 (m, 3H), 7.35 (d, J=8.1 Hz, 2H), 7.65 ppm (d, J=8.1 Hz, 2H);
13C NMR (CDCl3, 75 MHz, TMS) (two diastereoisomers): d=14.9, 15.0,
21.4, 21.4, 23.4, 24.5, 33.3, 35.7, 46.9, 47.3, 50.7, 52.1, 66.8, 66.9, 67.6, 67.9,
68.9, 70.86, 70.93, 71.2, 103.6, 105.4, 127.7, 127.8, 129.6, 129.7, 131.9,
132.2, 143.6, 143.9 ppm; MS (EI): m/z (%): 114 [M+À241, 72.3], 155 [M+
À200, 17.2], 200 [M+À155, 100.0]; HRMS: m/z: calcd for C17H25NO5S:
355.1453; found: 355.1460.
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Acknowledgements
We thank the Shanghai Municipal Committee of Science and Technology
(04 JC14083, 06XD14005) and the National Natural Science Foundation
of China for financial support (20472096, 203900502, 20672127, and
20732008).
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Received: December 10, 2007
Revised: May 13, 2008
Published online: July 4, 2007
7018
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Chem. Eur. J. 2008, 14, 7011 – 7018