A facile approach to spirocyclic butenolides through cascade cyclization/oxidative cleavage reactions of (Z)-enynols catalyzed by gold under dioxygen atmosphere

Article abstract of DOI:10.1016/j.jorganchem.2008.10.046

A facile approach for the syntheses of spirocyclic butenolides through cascade cyclization/oxidative cleavage reactions of (Z)-enynols bearing cyclic substituents at the C-1 position catalyzed by gold under dioxygen atmosphere has been developed. A variet

Full text of DOI:10.1016/j.jorganchem.2008.10.046

Journal of Organometallic Chemistry 694 (2009) 502–509
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A facile approach to spirocyclic butenolides through cascade
cyclization/oxidative cleavage reactions of (Z)-enynols catalyzed
by gold under dioxygen atmosphere
*
Feijie Song, Yuanhong Liu
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu,
Shanghai 200032, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 22 May 2008
Received in revised form 15 September 2008
Accepted 29 October 2008
Available online 6 November 2008
A facile approach for the syntheses of spirocyclic butenolides through cascade cyclization/oxidative
cleavage reactions of (Z)-enynols bearing cyclic substituents at the C-1 position catalyzed by gold under
dioxygen atmosphere has been developed. A variety of substituted butenolides was constructed in a reg-
ioselective manner from suitably substituted (Z)-2-en-4-yn-1-ols. (Z)-Enynols substituted both at C2 and
C3-position afforded the spirocyclic butenolides in moderate to good yields, C-2 unsubstituted (Z)-eny-
nols afforded the products in moderate yields, and the C-3 unsubstituted (Z)-enynols afforded the desired
products in low yields.
Keywords:
Gold catalysis
(Z)-Enynols
Ó 2008 Elsevier B.V. All rights reserved.
Cyclization
Oxidative cleavage
Spirocyclic butenolides
1. Introduction
2. Results and discussion
Spirolactones such as spirocyclic butenolides constitute an
important class of heterocyclic compounds due to the fact that
they widely occur as key structural subunits in natural products
and synthetic products. In addition, a high number of these com-
pounds has displayed useful biological activities which can find a
variety of applications in pharmaceutical use [1]. For example, nat-
urally occurring Lambertellol A [1d] exhibits remarkable growth
inhibition of spores, Securinine exhibits antimalarial and antibac-
terial activity [1d], man-made spirodiclofen are highly active acari-
cides and insecticides [1h] (Fig. 1). Therefore, the development of
synthetic routes that allow the facile assembly of spirocyclic bute-
nolides remains an important objective [2].
Recently we reported a new approach to 2(5H)furanone deriva-
tives through gold-catalyzed [3,4] cascade cyclization/oxidative
cleavage reactions of (Z)-enynols with molecular oxygen [5]. This
strategy provided an efficient route to fully substituted lactones
under mild conditions from readily available starting materials.
Especially, this methodology was applicable to the synthesis of spi-
rocyclic butenolides. In this paper, we present our detailed studies
of gold-catalyzed approach to spirocyclic butenolides from (Z)-
enynols bearing a cyclic substituent at the C-1 position (Scheme 1).
2.1. Preparation of substituted (Z)-2-en-4-yn-1-ols bearing a cyclic
substituent at C-1
We recently reported an efficient synthetic approach to stereo-
defined (Z)-enynols via zirconium-mediated cross-coupling reac-
tions of three different components involving alkynes, ketones,
and alkynyl bromides in a one-pot procedure [6]. Thus, a variety
of (Z)-enynols 3 bearing the substituents both at C-2 and C-3 and
a cyclic group at C-1 were readily synthesized employing cyclic ke-
tones as substrates by this method. According to our previous re-
port, when an alkyl group was used as a terminal group of
alkyne moiety, the cyclization/cleavage reaction proceeded much
faster than the corresponding phenyl-substituted one [5]. Thus in
most cases, enynols bearing a butyl group at the C-5 position were
synthesized. The results are shown in Table 1. Cyclic ketones such
as cycloheptanone, cyclooctanone or even cyclododecanone with
large-membered ring were well suitable for the reaction, furnish-
ing the corresponding enynols 3b–e in 43–71% yield (Table 1, en-
tries 2–5), however, cyclopentanone only afforded a 26% yield of
3a (Table 1, entry 1). The reaction of zirconacycles bearing an alke-
nyl substituent with 4-methylcyclohexanone also gave a low yield
of 3h (17%, Table 1, entry 8). As for alkynes, alkyl, aryl, heteroaryl,
and TMS (to afford E-3g) substituted alkynes were all compatible
with this coupling reaction.
* Corresponding author. Tel.: +86 21 54925135; fax: +86 21 64166128.
E-mail address: yhliu@mail.sioc.ac.cn (Y. Liu).
0022-328X/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2008.10.046

F. Song, Y. Liu / Journal of Organometallic Chemistry 694 (2009) 502–509
503
H
O
O
O
O
O
n
H
O
HO
Cl
H
OH
H
Spirocyclic butenolide
O
Spirofragilide
Stypolactone
O
OH
O
O
O
O
H
Cl
N
O
OH
O
O
H
Spirodiclofen
(-)-Securinine
Lambertellol A
Fig. 1. Some representative compounds bearing the spirocyclic butenolide moiety.
R4
R3
7). C-2-alkenyl-substituted (Z)-enynol 3h afforded 7h in moderate
yield of 50% (Table 2, entry 8).
R4
R3
R2
R1
R2
R1
cat. Au/Ag
THF, O2, 50 oC
Enynols unsubstituted at C-3 proved to be less favorable with
respect to analogous fully substituted substrates 3a–h. As illus-
trated in Table 3, C-2 phenyl-substituted enynols 3i and 3j afforded
the desired products 7i and 7j in 31% and 34% yields, respectively,
along with several undefined byproducts (Table 3, entries 1 and 2).
Enynols unsubstituted at C-2 afforded the desired products in
moderate yields. For example, C-3-alkyl or phenyl-substituted
(Z)-enynols 3k and 3l generated the desired spirolactone 7k and
7l in moderate yields of 53% and 61%, respectively (Table 3, entries
3 and 4). However, C-3 TMS substituted enynol 3n only resulted in
a low yield of 7m (22% at 50 °C, decreasing the reaction tempera-
ture to room temperature could not give better result). We
envisioned that this may be due to the less stability of a butyl-
substituted dihydrofuran intermediate from a C5-butyl-substi-
tuted enynol 3n. It was pleased to find that a higher yield of 7m
(59%) was achieved when changing the substrate 3n to a C5-phe-
nyl-substituted 3o (Table 3, entry 6). It was noteworthy that when
chiral (Z)-enynol bearing a bulky substituent at C-1 position was
employed, the desired product 7n was obtained in 44% yield with-
out any loss of enantiomeric excess (Table 3, entry 7). The structure
of 7n was further confirmed by X-ray crystallographic analysis
(Fig. 2).
O
O
HO
R5
Scheme 1.
(Z)-Enynols bearing a substituent at the C-2 position were pre-
pared by the lithium–bromine exchange reaction of (Z)-1-en-3-yn-
1-bromide 4 [7] with n-BuLi at ꢀ78 °C followed by the addition
reaction of cyclic ketones with the organolithium intermediate.
Using this strategy, C-2 phenyl-substituted (Z)-enynols 3i and 3j
were synthesized in 54% and 36% yields, respectively (Scheme 2).
(Z)-Enynols bearing a substituent at the C-3 position were pre-
pared by the Sonogashira coupling reaction of iodinated allylic
alcohols with terminal alkynes. The iodide precursors were conve-
niently synthesized from the corresponding propargylic alcohols 5
by their reaction with lithium aluminum hydride or Red-Al (Red-
Al = sodium bis(2-methoxyethoxy)aluminumhydride) followed by
iodination of the organoaluminum intermediate (Scheme 3) [8].
A variety of enynols bearing alkyl, aryl and TMS groups (E-3n–o)
could be easily synthesized by this reaction. It is noteworthy that
the chiral (Z)-enynol 3p could be obtained without any racemiza-
tion, as determined by chiral-column HPLC analysis.
2.3. Mechanism aspects
2.2. Synthesis of spirocyclic butenolides via gold-catalyzed cyclization/
cleavage reactions with molecular oxygen
To elucidate the reaction mechanism, we carried out the oxida-
tive cleavage reaction from dihydrofuran 8. During the further
investigation of this reaction [9], we found that the conversion of
dihydrofuran 8 to the butenolide 7 could proceed without the
use of a gold catalyst (Table 4). In the case of a dihydrofuran 8a
with R1 = Me, R2–R5 = Ph, the oxidation reaction required longer
reaction time compared with the use of gold catalyst, and lower
yields were obtained (without gold catalyst, the reaction time var-
ied from 28 h to 51 h, and the yields were in a range of 66–80%; in
the presence of gold(I) catalyst, the reaction completed in 18–22 h
with the yields of 89–94%, Table 4, entries 1–2). A similar result
was also obtained in spirocyclic substrate 8b, especially, the reac-
tion time could be further decreased to 18 h when 10 mol% gold
catalyst was employed (without gold catalyst, 38 h, Table 4, entries
3 and 5). In the case of butyl-substituted 8c, a higher yield of 86%
was observed with the use of gold catalyst (Table 4, entry 7). Thus
the gold catalyst may play a role in the step of oxidative cleavage
reaction. Controlled experiments showed that the cleavage of the
C@C double bond of dihydrofuran 8 to the butenolide 7 was com-
pletely suppressed in the presence of a radical scavenger [5], such
With various (Z)-enynols in hand, we were next interested in
applying the gold-catalyzed cyclization/oxidative cleavage reac-
tion of enynols with dioxygen for the synthesis of spirolactones.
The synthesis of fully substituted spirocyclic butenolides was first
investigated under the optimized reaction conditions, and the re-
sults are summarized in Table 2. Alkyl, alkenyl, aryl, heteroaryl
and TMS groups in enynols were all compatible with this reaction,
furnishing the desired products in 44–87% yield. It is noteworthy
that the cyclization of (Z)-enynols substituted with phenyl or 2-
thienyl groups at C-2 and C-3 proceeds smoothly to form 7a–e in
good yields (70–87%, Table 2, entries 1–5) regardless of the size
of the ring substituted at C-1 (5–8 and 12-membered rings). The
reactions of enynols with alkyl or TMS substituent at C-3 position
afforded the desired products in much lower yield under the pres-
ent reaction conditions (32% for 7f, 17% for 7g). However, when the
reactions were carried out at room temperature, the yields could
be improved to 52% and 44%, respectively (Table 2, entries 6 and

504
F. Song, Y. Liu / Journal of Organometallic Chemistry 694 (2009) 502–509
Table 1
Synthesis of fully substituted enynols.
R1
R2
R1
R1
2.0 CuCl, 2.0 LiCl
R2
R2
O
1.5Bu
rt, 36 h
Br
n
n
Cp2Zr
Cp2Zr
HO
O
n
Bu
Ph
1
2
3
Entry
1
R1
R2
Ketone
Product
Yielda (%)
26
Ph
Ph
Cyclopentanone
3a
Ph
HO
Bu
2
3
Ph
Ph
Ph
Ph
Cycloheptanone
Cyclooctanone
3b
3c
43
48
Ph
Ph
Ph
HO
HO
HO
Bu
Bu
Ph
4
5
Ph
Ph
Cyclododecanone
Cyclododecanone
3d
3e
66
71
Ph
Ph
Bu
Thi
Thib
Thi
Thi
HO
Bu
6
7
Et
Et
a
-Tetralone
-Tetralone
3f
51
67
Et
Et
HO
Bu
TMS
TMS
Me
a
3g
Me
HO
Bu
Bu
Bu
8
Ph
1-Hexenyl
4-Methylcyclohexanone
3h
17c
Ph
Me
HO
Bu
a
Isolated yields.
b
c
Thi = 2-thienyl.
One of the diastereomer was isolated, the stereochemistry of 3h was not defined.
as 2,6-di-tert-butyl-p-cresol or 4-hydroxy-TEMPO, implying that a
radical species is involved.
A possible mechanism for oxidative cleavage reaction is de-
picted in Scheme 4. It was known that enol ether radical cations
are readily produced by chemical or electrochemical oxidations
[10]. Thus, at first, a radical cation 9 was generated. As proposed
by Sakuragi and co-workers [10a], this step may involve the forma-
tion of a charge transfer complex between enol ether 8 and oxygen.
9 reacted with the triplet ground state oxygen to give radical cation
10. Further electron transfer from 8 to 10 would generate an ionic

F. Song, Y. Liu / Journal of Organometallic Chemistry 694 (2009) 502–509
505
Ph
Ph
Ph
Br
i) n-BuLi, -78 oC
ii) cyclic ketone
N Bn
HO
3i, 54%
HO
Bu
Bu
Bu
3j, 36%
4
Scheme 2.
R1
R2
cat. Pd(0)/CuI
R1
OH
i) LAH/MeONa, reflux
or Red-Al
R1
I
HO
HO
ii) I2
R2
Ph
5
6
3
3k, R1=R2=n-Bu, 54%
3l, R1=Ph, R2=n-Bu, 78%
3m, R1=Ph, R2=Ph, 84%
3n, R1=TMS, R2=n-Bu, 28%
3o, R1=TMS, R2=Ph, 52%
HO
Bu
3p, 48%,
98% ee
note: all the above yields are overall yields.
Scheme 3.
intermediate 11, this is followed by decomposition of 11 to afford
the butenolide 12. A similar reaction mechanism was also sug-
gested in the heat assisted C@C bond cleavage reactions [10a,11].
Gold catalyst may participate in the process [12] since a faster
reaction rate was observed in the case of phenyl (R5) substituted
dihydrofurans.
In summary, we have developed a facile approach for the syn-
thesis of spirocyclic butenolides through gold-catalyzed cleavage
of a carbon–carbon triple bond in (Z)-enynols bearing cyclic sub-
stituents at the C-1 position under dioxygen atmosphere. A variety
of substituted butenolides was constructed in a regioselective
manner from suitably substituted (Z)-2-en-4-yn-1-ols. (Z)-Enynols
substituted both at C2 and C3-position afforded the butenolides in
moderate to good yields, C-2 unsubstituted (Z)-enynols afforded
the products in moderate yields, and the C-3 unsubstituted (e.g.
C2-phenyl-substituted) (Z)-enynols afforded the desired products
in low yields.
lution mass spectra were obtained by using HP5989A and Waters
Micromass GCT mass spectrometers or IonSpec 4.7 T FTMS mass
spectrometers. Elemental analyses were performed on an Italian
Carlo-Erba 1106 analyzer. Melting point determinations were ob-
tained on a SGW X-4 apparatus and are uncorrected. Single crystal
X-ray diffraction data were collected on Bruker SMART APEX dif-
fractiometers. The characterization data of compound 7f has been
reported [5].
3.2 A general procedure for the gold-catalyzed synthesis of spirocyclic
butenolides from (Z)-enynols
(Z)-Enynols 3 (0.3 mmol) in THF (5 mL) was added to a 25 mL
Schlenk tube. Oxygen was gently bubbled through the resulting
solution via a needle. To the above solution at 50 °C were added
(Ph3P)AuCl (0.12 mL, 0.006 mmol, 2 mol%) and AgOTf (0.12 mL,
0.006 mmol, 2 mol%) successively. After the reaction was complete
as monitored by thin-layer chromatography, the solvent was re-
moved in vacuo and the residue was purified by chromatography
on silica gel to afford the spirocyclic butenolides 7.
3. Experimental
3.1. General
3.2.1. 3,4-Diphenyl-1-oxa-spiro[4,4]non-3-en-2-one (7a)
Column chromatography on silica gel (petroleum ether:ethyl
acetate = 35:1) afforded the title product as white solid in 80% iso-
lated yield. M.p. 153–155.5 °C; 1H NMR (CDCl3, Me4Si) d 1.72–1.81
(m, 2H), 1.91–2.12 (m, 6H), 7.19–7.24 (m, 5H), 7.38–7.40 (m, 5H);
13C NMR (CDCl3, Me4Si) d 24.38, 36.12, 96.06, 127.12, 128.01,
128.05, 128.24, 128.84, 128.92, 128.98, 129.66, 132.34, 163.16,
171.32; Anal. Calc. for C20H18O2: C, 82.73; H, 6.25. Found: C,
82.60; H, 6.50%.
All reactions concerning zirconacycles were carried out using
standard Schlenk techniques under nitrogen. THF was distilled
from sodium and benzophenone. Zirconocene dichloride and
EtMgBr (1.0 M solution in THF) were purchased from Aldrich
Chemical Company. Alkynes such as 3-Hexyne or diphenylacety-
lene were used as purchased. (Z)-(1-Bromooct-1-en-3-ynyl)ben-
zene 4 was synthesized according to the literature procedure [7].
AuCl(PPh3) was prepared according to the published method
[13]. AuCl(PPh3) and AgOTf were used as a 0.05 M solution in THF.
1H and 13C NMR spectra were recorded at 300 and 75.4 MHz,
respectively, on Varian XL-300 MHz spectrometer at room temper-
ature, and in CDCl3 (containing 0.03% TMS) solutions. 1H NMR
spectra was recorded with tetramethylsilane (d = 0.00 ppm) as
internal reference; 13C NMR spectra was recorded with CDCl3
(d = 77.00 ppm) as internal reference. Mass spectra and high-reso-
3.2.2. 3,4-Diphenyl-1-oxa-spiro[4,6]undec-3-en-2-one (7b)
Column chromatography on silica gel (petroleum ether:ethyl
acetate = 35:1) afforded the title product as light yellow solid in
78% isolated yield. M.p. 169–170 °C; 1H NMR (CDCl3, Me4Si) d
1.39–1.56 (m, 4H), 1.68–1.74 (m, 2H), 1.86–2.08 (m, 6H), 7.19–
7.21 (m, 5H), 7.34–7.40 (m, 5H); 13C NMR (CDCl3, Me4Si) d 22.94,

506
F. Song, Y. Liu / Journal of Organometallic Chemistry 694 (2009) 502–509
Table 2
The synthesis of fully substituted spirocyclic butenolides.
R2
R1
R2
R1
2 mol% AuCl(PPh3)/AgOTf
O2, THF, 50 ºC
O
O
HO
n
n
Bu
3
7
Entry
1
Enynol
R1
R2
Time (h)
2.5
Product
Yielda (%)
80
3a
Ph
Ph
(7a)
(7b)
(7c)
Ph
Ph
Ph
O
O
2
3
3b
3c
Ph
Ph
Ph
Ph
3
78
82
Ph
O
O
O
2.5
Ph
Ph
Ph
O
4
5
6
3d
3e
3f
Ph
Ph
Thi
Et
3
(7d)
(7e)
(7f)
87
70
Ph
O
O
O
O
Thib
7.5
Thi
O
Thi
Et
5
52c
Et
O
Et
7
3g
3h
Me
TMS
6
4
(7g)
(7h)
44d
TMS
O
Me
O
8
1-Hexenyl
Ph
50
Bu
Ph
O
Me
O
a
Isolated yields.
Thi = 2-thienyl.
The reaction was carried out at room temperature.
b
c
d
The reaction was first carried out under N2 atmosphere at room temperature for 0.5 h, and then O2 bubbling at the same temperature for 6 h.
28.41, 37.25, 90.38, 125.44, 127.84, 127.96, 128.14, 128.77, 128.84,
129.04, 129.57, 132.76, 167.48, 171.67; Anal. Calc. for C22H22O2: C,
82.99; H, 6.96. Found: C, 83.26; H, 7.16%.
5H); 13C NMR (CDCl3, Me4Si) d 21.96, 23.47, 27.52, 33.52, 89.78,
125.55, 127.77, 127.97, 128.13, 128.80, 128.83, 129.09, 129.61,
133.05, 168.38, 171.66; Anal. Calc. for C23H24O2: C, 83.10; H,
7.28. Found: C, 83.35; H, 7.40%.
3.2.3. 3,4-Diphenyl-1-oxa-spiro[4,7]dodec-3-en-2-one (7c)
Column chromatography on silica gel (petroleum ether:ethyl
acetate = 35:1) afforded the title product as white solid in 82% iso-
lated yield. M.p. 135–137 °C; 1H NMR (CDCl3, Me4Si) d 1.39–1.55
(m, 8H), 1.90–2.11 (m, 6H), 7.19–7.22 (m, 5H), 7.32–7.40 (m,
3.2.4. 3,4-Diphenyl-1-oxa-spiro[4,11]hexadec-3-en-2-one (7d)
Column chromatography on silica gel (petroleum ether:ethyl
acetate = 35:1) afforded the title product as white solid in 87% iso-
lated yield. M.p. 177–179 °C; 1H NMR (CDCl3, Me4Si) d 1.26–1.36

F. Song, Y. Liu / Journal of Organometallic Chemistry 694 (2009) 502–509
507
Table 3
Synthesis of spirocyclic butenolides from C-2 or C-3-substituted enynols.
R2
R1
R2
R1
2 mol% AuCl(PPh3)/AgOTf
O2, THF, 50 ºC
X
O
X
O
HO
R3
1
7
Entry
1
Enynol
R1
R2
H
R3
Time (h)
12
Product
Yielda (%)
31
3i
Ph
Bu
Ph
O
O
(7i)
2
3j
Ph
H
Bu
6
34
Ph
O
N Bn
O
(7j)
3
4
3k
3l
H
H
Bu
Ph
Bu
Bu
3
3
53
61
Bu
O
O
(7k)
Ph
O
O
(7l)
5
3n
H
TMS
Bu
3
22
TMS
O
O
(7m)
6
7
3o
3p
H
H
TMS
Ph
Ph
Bu
26
3
(7m)
59
44b
Ph
O
O
(7n)
a
Isolated yields.
98% ee as determined by chiral HPLC.
b
Fig. 2. The X-ray crystal structure of compound 7n.

508
F. Song, Y. Liu / Journal of Organometallic Chemistry 694 (2009) 502–509
Table 4
22.85, 23.16, 25.17, 26.20, 33.06, 90.77, 122.59, 126.76, 127.66,
127.83, 128.78, 128.99, 130.92, 131.89, 156.30, 169.89; Anal. Calc.
for C23H28O2S2: C, 68.96; H, 7.05. Found: C, 69.14; H, 7.01%.
Oxidative cleavage reaction of 2,5-dihydrofuran 8.
R4
R3
R2
R1
R4
R3
R2
R1
H
(Ph3P)AuOTf
3.2.6. Spirocyclic butenolide (7g)
O
O
O
Column chromatography on silica gel (petroleum ether:ethyl
acetate = 35:1) afforded the title product as white solid in 44% iso-
lated yield. M.p. 101–103 °C; 1H NMR (CDCl3, Me4Si) d 0.36 (s, 9H),
1.91 (s, 3H), 1.87–2.14 (m, 4H), 2.74–2.95 (m, 2H), 6.84 (d,
J = 7.5 Hz, 1H), 7.12–7.26 (m, 3H); 13C NMR (CDCl3, Me4Si) d
ꢀ0.91, 14.49, 19.55, 29.46, 33.78, 88.50, 126.57, 126.68, 126.97,
128.73, 129.54, 131.70, 138.53, 175.60, 179.00; Anal. Calc. for
C17H22O2Si: C, 71.28; H, 7.74. Found: C, 71.01; H, 7.56%.
R5
THF, O2, 50 ºC
8
7
Entry Dihydrofuran
Catalyst
(%)
Time (h) Product Yielda (%)
1
–
28–51b
7o
66–80b
Ph
Ph
H
O
Ph
Ph
8a
3.2.7. Spirocyclic butenolide (7h)
18–22b
38
7o
7l
89–94b
40
Column chromatography on silica gel (petroleum ether:ethyl
acetate = 200:1) afforded the title product as white solid in 50%
isolated yield. M.p. 89–92 °C; 1H NMR (CDCl3, Me4Si) d 0.85 (t,
J = 6.9 Hz, 3H), 0.92 (d, J = 6.3 Hz, 3H), 1.21–1.39 (m, 5H), 1.44–
1.57 (m, 2H), 1.63–1.79 (m, 6H), 2.01–2.08 (m, 2H), 5.77 (d,
J = 15.9 Hz, 1H), 6.87–6.97 (m, 1H), 7.16–7.19 (m, 2H), 7.45–7.47
(m, 3H); 13C NMR (CDCl3, Me4Si) d 13.81, 22.14, 22.20, 30.43,
30.91, 30.96, 33.43, 33.69, 86.46, 117.96, 123.87, 127.94, 128.66,
128.76, 132.31, 138.82, 163.86, 171.30; HRMS (EI) for C22H28O2:
calc. 324.2089, found 324.2082.
2
2
–
3
Ph
H
O
Ph
c
8b
4
5
2
10
26
18
7l
7l
65
66
6
–
3
7p
68
Ph
Ph
3.2.8. 4-Phenyl -1-oxa-spiro[4,5]dec-3-en-2-one (7i)
H
Column chromatography on silica gel (petroleum ether:ethyl
acetate = 25:1) afforded the title product in 31% isolated yield. 1H
NMR (CDCl3, Me4Si) d 1.16–1.29 (m, 1H), 1.68–1.84 (m, 7H),
1.87–2.01 (m, 2H), 6.12 (s, 1H), 7.40–7.49 (m, 5H); 13C NMR (CDCl3,
Me4Si) d 22.12, 24.50, 34.42, 89.43, 115.64, 127.52, 128.88, 130.30,
130.92, 171.82, 172.76. The spectral data is in agreement with re-
ported data [14].
O
o-ClC6H4
Bu
8c
7
2
3
7p
86
cCompound 8b was prepared in 76% yield from 3m catalyzed by 2 mol%
(Ph3P)AuOTf under N2 for 1 h.
a
Isolated yields.
The reaction was repeated for several times.
b
3.2.9. 8-Benzyl-4-phenyl-1-oxa-8-aza-spiro[4.5]dec-3-en-2-one (7j)
Column chromatography on silica gel (petroleum ether:ethyl
acetate = 6:1) afforded the title product as light yellow solid in
34% isolated yield. 1H NMR (CDCl3, Me4Si) d 1.67 (d, J = 12.3 Hz,
2H), 2.38 (td, J = 12.9 Hz, J = 4.5 Hz, 2H), 2.54 (t, J = 11.4 Hz, 2H),
2.86–2.90 (m, 2H), 3.58 (s, 2H), 6.21 (s, 1H), 7.24–7.33 (m, 5H),
7.44–7.48 (m, 3H), 7.51–7.55 (m, 2H); 13C NMR (CDCl3, Me4Si) d
34.41, 49.40, 62.97, 87.27, 115.87, 127.06, 127.57, 128.19, 128.92,
129.05, 130.37, 130.48, 137.94, 171.28, 171.58; HRMS (EI) for
C21H21NO2: calc. 319.1572, found 319.1566.
(m, 18H), 1.91–2.08 (m, 4H), 7.18–7.24 (m, 5H), 7.26–7.32 (m, 2H),
7.34–7.39 (m, 3H); 13C NMR (CDCl3, Me4Si) d 20.30, 22.56, 22.95,
25.28, 26.24, 32.98, 90.82, 126.73, 127.83, 127.92, 128.06, 128.75,
128.83, 129.23, 129.60, 133.36, 166.75, 171.32; Anal. Calc. for
C27H32O2: C, 83.46; H, 8.30. Found: C, 83.54; H, 8.32%.
3.2.5. 3,4-Di(2-thienyl)-1-oxa-spiro[4,11]hexadec-3-en-2-one (7e)
Column chromatography on silica gel (petroleum ether:ethyl
acetate = 50:1) afforded the title product in 70% isolated yield.
M.p. 127–129 °C; 1H NMR (CDCl3, Me4Si) d 1.26–1.44 (m, 18H),
1.87–2.05 (m, 4H), 6.96–6.99 (m, 1H), 7.13–7.18 (m, 2H), 7.26–
7.29 (m, 1H), 7.56–7.60 (m, 2H); 13C NMR (CDCl3, Me4Si) d 20.22,
3.2.10. 3-Butyl-1-oxa-spiro[4,5]dec-3-en-2-one (7k)
Column chromatography on silica gel (petroleum ether:ethyl
acetate = 90:1) afforded the title product as light yellow oil in
R4
R3
R2
R1
R4
R3
R2
R4
R3
R2
O
H
+ O2
H
O
-
+ 8
e
+
+
O
R5
R1
R1
O
9
O
10
R5
R5
9
8
-
R4
R3
R2
R4
R3
R2
O
O
+ R5CHO
[O]
+
O
R1
R1
O
O
R5
11
12
R5COOH
Scheme 4.

F. Song, Y. Liu / Journal of Organometallic Chemistry 694 (2009) 502–509
509
53% isolated yield. 1H NMR (CDCl3, Me4Si) d 0.92 (t, J = 6.9 Hz, 3H),
1.30–1.42 (m, 2H), 1.48–1.79 (m, 12H), 2.25 (td, J = 7.8 Hz,
J = 1.2 Hz, 2H), 7.02 (s, 1H); 13C NMR (CDCl3, Me4Si) d 13.70,
22.18, 22.49, 24.59, 24.76, 29.46, 34.89, 86.00, 132.97,
152.44, 173.38; HRMS (EI) for C13H20O2: calc. 208.1463, found
208.1467.
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif. Supplementary data associated with this article
can be found, in the online version, at doi:10.1016/
j.jorganchem.2008.10.046.
References
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3.2.11. 3-Phenyl -1-oxa-spiro[4,5]dec-3-en-2-one (7l)
Column chromatography on silica gel (petroleum ether:ethyl
acetate = 90:1) afforded the title product as white solid in 61% iso-
lated yield. M.p. 107–109 °C; 1H NMR (CDCl3, Me4Si) d 1.36–1.45
(m, 1H), 1.67–1.87 (m, 9H), 7.34–7.43 (m, 3H), 7.57 (s, 1H), 7.84–
7.87 (m, 2H); 13C NMR (CDCl3, Me4Si) d 22.42, 24.56, 34.84,
85.29, 126.97, 128.50, 129.05, 129.67, 130.08, 152.42, 171.13; Anal.
Calc. for C15H16O2: C, 78.92; H, 7.06. Found: C, 78.84; H, 7.12%.
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[2] (a) For the synthesis of spirocyclic butenolides, see: P. Langer, U. Albrecht,
Synlett (2002) 1841;
3.2.12. 3-Trimethylsilyl-1-oxa-spiro[4,5]dec-3-en-2-one (7m)
Column chromatography on silica gel (petroleum ether:ethyl
acetate = 150:1) afforded the title product as white solid in 22%
isolated yield. M.p. 131–133 °C; 1H NMR (CDCl3, Me4Si) d 0.24 (s,
9H), 1.35–1.41 (m, 1H), 1.64–1.78 (m, 9H), 7.46 (s, 1H)); 13C
NMR (CDCl3, Me4Si) d ꢀ2.14, 22.46, 24.62, 34.52, 88.38, 132.82,
168.37, 175.14; HRMS (EI) for C12H20O2Si: calc. 224.1233, found
224.1232.
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3.2.13. Spirocyclic butenolide (7n)
Column chromatography on silica gel (petroleum ether:ethyl
acetate = 60:1) afforded the title product as light yellow solid in
44% isolated yield. M.p. 119–120 °C;
½
a 2D0
ꢁ
¼ ꢀ51:3 (c 1.035,
(b) G.C. Bond, Catal. Today 72 (2002) 5;
(c) A.S.K. Hashmi, Gold Bull. 36 (2003) 3;
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(j) A.S.K. Hashmi, Chem. Rev. 107 (2007) 3180;
CHCl3); HPLC (Chiral AD-H): 98% ee, detected at 254 nm; flow rate
0.5 mL/min; eluent: hexanes/isopropanol = 90:10. 1H NMR (CDCl3,
Me4Si) d 0.77 (s, 3H), 0.93 (s, 3H), 1.17 (s, 3H), 1.21–1.30 (m, 1H),
1.47–1.55 (m, 1H), 1.60–1.70 (m, 1H), 1.75 (d, J = 14.1 Hz, 1H),
1.83–1.93 (m, 2H), 2.39 (dt, J = 13.8 Hz, J = 3.9 Hz, 1H), 7.33–7.43
(m, 3H), 7.55 (s, 1H), 7.86 (dd, J = 7.8 Hz, J = 1.5 Hz, 2H); 13C
NMR (CDCl3, Me4Si) d 9.62, 20.16, 20.35, 27.10, 31.58, 41.73,
44.71, 49.34, 54.16, 94.02, 126.89, 128.45, 128.91, 129.57,
130.49, 151.22, 171.18; Anal. Calc. for C19H22O2: C, 80.82; H,
7.85. Found: C, 80.49; H, 7.85%.
(k) S. Ma, S. Yu, Z. Gu, Angew. Chem., Int. Ed. 45 (2006) 200.
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Schwarz, J.-H. Choi, T.M. Frost, Angew. Chem. 112 (2000) 2382. Angew. Chem.,
Int. Ed. 39 (2000) 2285;
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[9] In our original paper (Ref. [5]), we reported that no oxidative cleavage reaction
was observed in the absence of Au(I) using dihydrofuran 8a as substrate.
However, during our further study of this reaction, we found that this reaction
indeed occurred without gold catalyst, although a longer reaction time and a
lower yield was obtained. After a series experiments, we found that the
impurities contained in the gas bag may stop the C@C bond cleavage reaction.
We noted that the reported reaction using 8a as substrate without gold
catalyst was carried out using a gas bag as the source of oxygen (only in this
case, we use gas bag, since this reaction was done at the early stage of the
project, all other reactions were carried out using cylinder as oxygen source).
[10] (a) T. Kanno, M. Hisaoka, H. Sakuragi, K. Tokumaru, Bull. Chem. Soc. Jpn. 54
(1981) 2330;
3.2.14. 2-Benzylidene-3-phenyl-1-oxa-spiro[4.5]dec-3-ene (8b)
Column chromatography on silica gel (petroleum ether) affor-
ded the title product as a light yellow solid in 76% isolated yield.
M.p. 112–114 °C; 1H NMR (CDCl3, Me4Si) d 1.37–1.48 (m, 1H),
1.56–1.73 (m, 5H), 1.79–1.93 (m, 4H), 5.42 (s, 1H), 6.31 (s, 1H),
7.09 (tt, J = 7.5 Hz, J = 1.2 Hz, 1H), 7.26–7.32 (m, 2H), 7.34–7.46
(m, 5H), 7.67 (d, J = 7.8 Hz, 2H); 13C NMR (CDCl3, Me4Si) d 22.94,
25.11, 36.02, 91.95, 97.60, 124.81, 127.56, 128.14, 128.21, 128.43,
128.48, 133.32, 136.99, 137.44, 138.73, 158.46; Anal. Calc. for
C22H22O: C, 87.38; H, 7.33. Found: C, 87.16; H, 7.14%.
Acknowledgments
(b) M. Newcomb, N. Miranda, M. Sannigrahi, X. Huang, D. Crich, J. Am. Chem.
Soc. 123 (2001) 6445;
We thank the National Natural Science Foundation of China
(Grant No. 20732008), Chinese Academy of Science, Science and
Technology Commission of Shanghai Municipality (Grant Nos.
08QH14030, 07JC14063) and the Major State Basic Research Devel-
opment Program (Grant No. 2006CB806105) for financial support.
(c) J.H. Horner, E. Taxil, M. Newcomb, J. Am. Chem. Soc. 124 (2002) 5402;
(d) D. Crich, D.-H. Suk, S. Sun, Tetrahedron: Asymmetry 14 (2003) 2861.
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mechanism, see: P. Lignier, F. Morfin, S. Mangematin, L. Massin, J.-L. Rousset, V.
Caps, Chem. Commun. (2007) 186.
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[14] A.R. Katritzky, D. Feng, H. Lang, J. Org. Chem. 62 (1997) 715.
Appendix A. Supplementary material
CCDC 686810 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The