Bronsted acid catalyzed cyclization of hydroxylated enynes: A concise synthesis of five-membered heterocycles

Article abstract of DOI:10.1002/chem.201002222

A mild and direct pathway for the formation of five-membered heterocyclic compounds from hydroxylated enynes has been developed. In this reaction, hydroxylated enynes were selectively transformed into five-membered heterocyclic compounds 2, with an allene

Full text of DOI:10.1002/chem.201002222

FULL PAPER
DOI: 10.1002/chem.201002222
Brønsted Acid Catalyzed Cyclization of Hydroxylated Enynes: A Concise
Synthesis of Five-Membered ACHTNUTRGNEHNUG eterocycles
Ke-Gong Ji,[a] Jin Chen,[a] Hai-Tao Zhu,[a] Fang Yang,[a] Ali Shaukat,[a] and
Yong-Min Liang*[a, b]
Abstract: A mild and direct pathway
for the formation of five-membered
heterocyclic compounds from hydroxy-
lated enynes has been developed. In
this reaction, hydroxylated enynes
were selectively transformed into five-
membered heterocyclic compounds 2,
with an allene moiety at the 3-position,
(0.1 mol%). When R1, R2 =Ph, diphe-
nylvinyl-2,3-dihydro-1H-pyrrole (2y)
was obtained. With HSbF6 (5 mol%)
as the catalyst, polycyclic skeletons 3
and 4 with adjacent stereocenters were
obtained. When R1 =H and R2 =sty-
rene, 1,3-dienyl-2,5-dihydro-1H-pyrrole
(6as) was formed. This Brønsted acid
catalyzed domino process involves the
formation of an allene carbocation in-
termediate, which can be readily
trapped by olefins to give various novel
five-membered heterocyclic skeletons.
Keywords: allenes · Brønsted acids ·
heterocycles · hydroxylated enynes ·
olefins
in
the
presence
of
F3CSO3H
Introduction
tive protocols, involving atom economic, environmentally
benign, and mild reaction conditions, for the straightforward
synthesis of heterocyclic rings are still of high demand in
modern organic synthesis.
In recent years, the annulation of heterocycles, especially
polyheterocyclic skeletons, has continued to attract the in-
terest of synthetic chemists due to the number of these com-
pounds that are extensively used as synthetic building
blocks and also appear as subunits in many natural products
that exhibit interesting biological activities.[1] Today, the
main challenges that organic chemists face is the production
of these architecturally complex molecules in facile and effi-
cient ways.[2] The cycloisomerization of enynes is one such
method, for which transition-metal catalysts, such as palladi-
um, platinum, gold, ruthenium, and rhodium, are found to
effectively promote the cyclization.[3] However, most of
these procedures require high loadings of expensive metal
catalysts and ligands. Moreover, the number of accessible
heterocyclic skeletons are limited. Therefore, new and effec-
Five-membered oxygen- or nitrogenated heterocycles are
important intermediates for the synthesis of pharmaceutical-
ly and biologically active molecules, such as (À)-domoic
acid,[4] isodomoic acid H,[5] kainic acid,[6] conessine,[7] and
(+)-intricarene.[8] Some efficient synthetic routes to these
skeletons have been reported, of which carbon–hetero for-
mation (through path a) and carbon–carbon formation
(through path b) catalyzed by transition metals are more
valuable (Scheme 1). In contrast, examples of the cyclization
or cycloisomerization reactions of hydroxylated enynes cata-
lyzed by Brønsted acids[9] have rarely been reported.
[a] Dr. K.-G. Ji, J. Chen, H.-T. Zhu, F. Yang, A. Shaukat,
Prof. Dr. Y.-M. Liang
Scheme 1. Some efficient synthetic routes to heterocyclic skeletons.
State Key Laboratory of Applied Organic Chemistry
Lanzhou University, Lanzhou 730000 (China)
Fax : (+86)931-891-2582
In the context of our ongoing efforts to construct various
functionalized heterocyclic structures,[10] we found that prop-
E-mail: liangym@lzu.edu.cn
e,f,11]
argyl carbocation B,[10
in resonance with allene cation
[b] Prof. Dr. Y.-M. Liang
State Key Laboratory of Solid Lubrication
Lanzhou Institute of Chemical Physics
Chinese Academy of Science, Lanzhou 730000 (P.R. China)
C, which can react with nucleophiles (e.g., hydroxy;
Scheme 2a), is a perfect intermediate for a domino process.
It is known that an olefin as a nucleophile can also react
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201002222.
À
with a carbocation to form a C C bond. Thus, we envi-
Chem. Eur. J. 2011, 17, 305 – 311
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305

Table 1. Optimization of the Brønsted acid catalyzed cascade reaction.[a]
Entry Catalyst [mol%]
Solvent[b] T [8C] t [min] Yield [%][c]
[d]
1
2
3
4
5
6
7
8
F3CSO3H (10)
F3CSO3H (5)
F3CSO3H (1)
F3CSO3H (0.3)
F3CSO3H (0.3)
F3CSO3H (0.1)
F3CSO3H (0.05)
TFA (0.1)
TsOH (0.1)
ClCH2COOH (0.1) CH2Cl2
HCl (0.1)
F3CSO3H (0.1)
F3CSO3H (0.1)
F3CSO3H (0.1)
F3CSO3H (0.1)
F3CSO3H (0.1)
F3CSO3H (0.1)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
RT
RT
RT
RT
0
0
0
0
0
0
0
0
0
0
0
0
0
5
5
2
2
2
–
–
–
–
[d]
[d]
[d]
45
81
79
60
trace
0
Scheme 2. a) Possible equilibrium. b) Design of the present domino pro-
cess.
5
5
180
180
180
180
5
30
30
30
30
30
9
10
11
12
13
14
15
16
17
CH2Cl2
DCE
THF
toluene
DMF
acetone
CH3CN
0
sioned that this type of propargyl alcohol 1 could undergo
the isomerization process with trace amounts of Brønsted
acid to form putative allene carbocation B’, which can be
readily trapped by nucleophiles (olefin in this case;
80
70
0
0
0
À
Scheme 2b). Herein, we report a novel C X (X=C, O)
0
bond formation from 1,6-hydroxylated enynes for the con-
struction of five-membered heterocyclic rings in the pres-
ence of Brønsted acids. Note, product 2 is an important
structural unit and is easily modified to a natural product,
such as kainic acid.[6]
[a] Conditions: 1a (0.3 mmol) with Brønsted acids in CH2Cl2 (3.0 mL).
[b] TFA=trifluoroacetic acid, DCE=dichloroethane, Ts=tosyl. [c] Iso-
lated yield. [d] Decomposed.
With the optimized conditions in hand, various represen-
tative hydroxylated enynes 1a–x were then subjected to the
optimized conditions, as depicted in Table 2. Thus, tandem
carbon–oxygen bond cleavage and carbon–carbon bond for-
mation of hydroxylated enynes 1a–x proceeded smoothly to
provide the corresponding allenes in moderate to good
yields, except 1p and 1r. From these results, it can be seen
that this reaction tolerated a variety of functional groups at
the ortho, meta, and para positions of the phenyl moiety in
substituted hydroxylated enynes, indicating that the steric
effect has little impact on this transformation. Hydroxylated
enynes with a heterocyclic ring, such as the furan nucleus,
can also afford the desired product (e.g., 2o in 54% yield).
However, the substrate scope cannot be further extended to
aliphatic hydroxylated enynes, such as 1p; this could be as-
Results and Discussion
Initially, we started by using N-(4-hydroxy-4-phenylbut-2-
ynyl)-4-methyl-N-(3-methylbut-2-enyl)benzenesulfonamide
(1a; 0.3 mmol) and trifluoromethanesulfonic acid (TfOH;
10 mol%) in CH2Cl2 at room temperature, but no desired
product was obtained (Table 1, entry 1). Lowering the cata-
lyst loading from 10 to 0.3 mol%, led to decomposition of
the starting material 1a (Table 1, entries 2–4). With an at-
tempt to get the predicted product, the reaction was carried
out at 08C in the presence of 0.3 mol% TfOH. To our de-
light, the desired product 3-(2-phenylvinylidene)-4-(prop-1-
en-2-yl)-1-tosylpyrrolidine (2a) was formed in 45% yield
after 2 min (Table 1, entry 5). On decreasing the amount of
catalyst to 0.1 mol%, a good yield of 81% of 2a was ob-
tained after 2 min (Table 1, entry 6). Lowering the catalyst
loading led to a slow conversion with the decreased yield of
2a (Table 1, entry 7). Other acids have also been applied to
the reaction. It was found that TFA gave the desired prod-
uct, albeit with a lower yield (Table 1, entry 8). With an at-
tempt to optimize the yield of the product, we further stud-
ied the influence of different reaction media (Table 1, en-
tries 12–17). From the results obtained, it can be seen that
only DCE and THF were efficient (Table 1, entries 12 and
13). Note, no 3-(2-phenylvinylidene)-4-(propan-2-ylidene)-1-
tosylpyrrolidine (3a) was observed during this reaction. The
reaction conditions were eventually optimized to 0.3 mmol
of 1, 0.1 mol% TfOH as the catalyst, 3 mL of CH2Cl2 as the
solvent at 08C (Table 1, entry 6).
À
cribed to the fact that the cleavage of C O bond could not
be occur in the presence of F3CSO3H (0.1 mol%). Note,
some oxygenated hydroxylated enynes can also participate
in this reaction. From the results, it can be seen that an elec-
tron-donating substituent at the R2 group hinders product
formation (1r), whereas an electron-withdrawing group
(e.g., Cl) and aliphatic group favors product formation (1s–
x).
To expand further the scope of the reaction, we also in-
vestigated hydroxylated enynes 1y and 1z. Surprisingly, het-
erocyclic diphenylvinyl 2y and 1, 3-diene 2z were obtained
in 28 and 80% yields, respectively (Scheme 3).
To have more insight of this type of reaction, we investi-
gated hydroxylated enyne 1aa (Table 3). Fortunately, the de-
sired polycyclic skeletons 3aa and 4aa were formed and iso-
lated in a total yield of 36% after 3 h in the presence of
TfOH (10 mol%). Other commonly used Brønsted acids,
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Chem. Eur. J. 2011, 17, 305 – 311

Brønsted Acid Catalyzed Cyclization of Hydroxylated Enynes
FULL PAPER
Table 2. F3CSO3H-catalyzed synthesis of heterocyclic allenes 2 from hydroxylated enynes 1.[a]
Heterocyclic Allenes 2
2a (81%)[b]
2 f (55%)
2k (62%)
2b (81%)
2g (53%)
2l (59%)
2c (67%)
2h (68%)
2m (61%)
2d (67%)
2i (62%)
2n (75%)
2e (60%)
2j (63%)
2o (54%)
2p (0%)
2q (52%)
2v (62%)
2r (–)[c]
2s (54%)
2x (60%)
2t (64%)
2u (64%)
2w (66%)
[a] Conditions: 1 (0.3 mmol) with TfOH (0.1 mol%) in CH2Cl2 (3.0 mL) at 08C. [b] Isolated yield. [c] Decomposed.
Table 3. Optimization of the cascade reaction of hydroxylated enyne
1aa.[a]
Catalyst ([mol%])
Yield [%][b]
3aa/4aa
TfOH (10)
TFA (10)
36
mixture
20:16
0
TsOH (10)
HNTf2 (10)
HSbF6 (10)
HSbF6 (5)
0
73
86
92
0
41:32
48:38
52:40
Scheme 3.
such as TFA, TsOH, HNTf2, and HSbF6, have also been ap-
plied to the reaction. It was found that the strong acid
HSbF6 gave the same products as those obtained from
TfOH, albeit with a better yield of 86%. On decreasing the
amount of HSbF6 to 5 mol%, a 92% yield was obtained
with a ratio of 3aa/4aa close to 5:4. The reaction conditions
were eventually optimized to 0.3 mmol of 1, 5 mol% of
HSbF6 as the catalyst, 3 mL of CH2Cl2 as the solvent at
room temperature.
[a] Tf=trifluoromethanesulfonyl. [b] Isolated yield.
With the optimized conditions in hand, various represen-
tative hydroxylated enynes 1aa–an were then subjected to
the optimized conditions, as depicted in Table 4. Tandem
carbon–carbon and carbon–oxygen bond formation of hy-
droxylated enynes 1aa–an proceeded smoothly to provide
the corresponding polycyclic skeletons in moderate to excel-
Chem. Eur. J. 2011, 17, 305 – 311
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307

Y.-M. Liang et al.
Table 4. HSbF6-catalyzed synthesis of polycyclic skeletons 3 and 4 from hydroxylated enynes 1.[a]
ring was not stable under
the
(Table 4, entry 8). The steric
effect of hydroxylated
reaction
conditions
enynes such as 1ai–ak was
also investigated; this had
an impact on this transfor-
mation (Table 4, entries 9–
11). To confirm the structur-
al assignment of products in
the present cascade reac-
tion, the relative configura-
tion of the products 3aj and
4aj were unambiguously as-
signed by X-ray crystallogra-
phy (Figure 1).[12] Substrates
1al–an, with 5-, 7-, and 8-
membered ring systems,
were also applied to the re-
action. Substrate 1al with
the 5-membered ring system
could not afford the desired
product, which might be due
to ring strain (Table 4,
entry 12). While, substrates
1am and 1an with 7- and 8-
membered ring systems, re-
spectively, gave an excellent
yield of the corresponding
products.
Entry Substrate
3/4
Yield Entry Substrate
[%][b]
3/4
Yield
[%][b]
[c]
1
1aa 52:40 92
8
9
1ah
–
2
1ab 50:40 90
1ai 36:36 72
3
4
1ac 55:35 90
10
11
1aj 52:18 70
1ad 44:44 88
1ak 58:30 88
HexahydrofuroACHTUNTRGNEUNG[3,4-
c]furan ring is very impor-
tant in organic synthesis.
Under the optimized condi-
tions, we also investigated a
range of oxygen-tethered
hydroxylated enynes 1ao–
aq, as shown in Scheme 4.
Fortunately, the reactions of
1ao–aq proceeded smoothly
and gave the desired
5
6
7
1ae 43:43 86
1af 58:22 80
1ag 69:22 91
12
13
14
1al
0
1am 65:33 96
hexahydrofuroACTHNUTRGNEUG[N 3,4-c]furan
1an 61:38 99
derivatives in moderate to
good yield (65–87%).
When carbon-tethered hy-
droxylated enyne 1ar was
subjected to the standard
conditions, a total yield of
[a] Conditions: 1 (0.3 mmol) with HSbF6 (5 mol%) in CH2Cl2 (3.0 mL) at room temperature (23–258C). [b] Isolated
yield. [c] Decomposed.
lent yields, except 1ah and 1al. From these results, it can be
seen that this reaction tolerated a variety of functional
groups at the meta and para positions of the phenyl moiety
in the substituted R1 group. As shown, the position of the
substituent on R1 had only a slight influence on the yield of
the products. Both electron-rich aryl groups and electron-
withdrawing groups showed good results (Table 4, entries 1–
7). Substrate 1ah with a heteroaromatic R1 group decom-
posed, which could be ascribed to the fact that the furan
77% of the polycyclic skeletons was isolated after 5 h, with
a ratio of 2ar and 3ar of 5:1 (Scheme 5).
A deuterium-labeling experiment was performed to rule
out a possible 1,4-hydrogen shift in the course of the mecha-
nism. As shown in Scheme 6, hydroxylated enyne [D]1aa
with HSbF6 (5 mol%) in wet CH2Cl2 at room temperature
produced the desired polycyclic skeletons [D]3aa with a
deuterium content of X=0.27 D and [D]4aa with a deuteri-
um content of X=0.92 D. The formation of product [D]3aa
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Brønsted Acid Catalyzed Cyclization of Hydroxylated Enynes
FULL PAPER
Scheme 6. Deuterium-labeling experiments.
was also confirmed by high-resolution mass spectrometry
and NMR spectroscopy.
We also investigated hydroxylated enyne 1as, and the de-
sired product 6as was obtained in 65% yield after 8 h. In
this reaction, intermediate allene alcohol 5as was observed,
demonstrating the fact that 6as was formed through a
domino carbon–carbon bond cleavage and isomerization in
the presence of H+ (Scheme 7).
Figure 1. X-ray structures of 3aj and 4aj.[13]
Scheme 7. HSbF6-catalyzed domino carbon–carbon bond cleavage for
6as.
On the basis of the above observations, we propose the
following plausible mechanisms for this cascade transforma-
tion (Scheme 8). 1) In the presence of trace amounts of H+,
the hydroxyl group of 1 is lost to give the putative allene
carbocation intermediate B,[13] which can be readily trapped
by olefin nucleophile to form carbocation intermediate C.
2) Intermediate C can lose a proton selectively to give the
heterocyclic allene 2 (path I). Alternatively, water as the nu-
cleophile can attack the carbocation intermediate C to form
intermediate D, which loses one molecule of water in the
presence of trace amounts of H+ to give the heterocyclic
allene 2 (path II). 3) When R1 and R2 are cyclohexylidene
substituents, water as the nucleophile attacks the carbocat-
ion intermediate C to form intermediates D1 and D2. 4) In-
termediate allene alcohol D1 follows the domino carbon–
carbon bond formation pathway in the presence of H+ and
affords the intermediate cation E1. 5) The hydroxyl group of
intermediate cation E1 may attack the allyl carbocation to
afford H1, which releases a proton to afford the polycyclic
skeleton 4. 6) The intermediate allene alcohol D2 also fol-
lows the domino carbon–carbon bond formation pathway in
Scheme 4. HSbF6-catalyzed hydroxylated enynes 1ao–aq.
Scheme 5. HSbF6-catalyzed hydroxylated enynes 1ar.
Chem. Eur. J. 2011, 17, 305 – 311
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309

Y.-M. Liang et al.
Scheme 8. Proposed mechanism.
the presence of H+ to afford the intermediate cation E2. Be-
cause of steric effects, the hydroxyl group of intermediate
cation E2 cannot attack the allyl carbocation and intermedi-
ate cation E2 may be in equilibrium with carbocation G2 via
intermediate F2 in the presence of H+. Thus, the hydroxyl
group of intermediate cation G2 attacks the allyl cation to
give H2, which loses a proton to afford the polycyclic skele-
ton 3.
before use from Na/benzophenone. All details of instruments that were
used for data characterization can be found in the Supporting Informa-
tion.
General procedure A: Brønsted acid catalyzed cyclization of hydroxylat-
ed enynes toward five-membered heterocyclic allenes 2a–2x: F3CSO3H
(0.0003 mmol, 0.1 mol%) was added to
a solution of hydroxylated
enynes 1 (0.30 mmol) in wet CH2Cl2 (3.0 mL) at 08C. Within minutes,
when the reaction was considered to be complete as determined by TLC
analysis, the reaction mixture was diluted with ethyl ether (40 mL),
washed with water, saturated brine, dried over Na2SO4, and evaporated
under reduced pressure. The residue was purified by column chromatog-
raphy on silica gel to afford the corresponding polycyclic skeletons 2a–x.
Compound 2a: Reaction time: 5 min; yield: 81%; 1H NMR (400 MHz,
CDCl3): d=7.75 (dd, J=8.0, 1.6 Hz, 2H), 7.36 (d, J=8.0 Hz, 2H), 7.29–
7.15 (m, 5H), 6.29–6.26 (m, 1H), 4.84–4.77 (m, 2H), 4.12–3.90 (m, 2H),
3.62–3.48 (m, 2H), 3.29–3.18 (m, 1H), 2.46 (s, 3H), 1.68 and 1.66 ppm
(2ꢁs, 3H); 13C NMR(100 MHz, CDCl3): d=198.0, 197.9, 143.8, 142.5,
142.2, 133.9, 133.7, 133.0, 132.9, 129.8, 129.7, 128.6, 127.9, 127.4, 127.0,
113.2, 105.0, 104.9, 99.4, 99.3, 52.3, 49.8, 49.8, 49.5, 49.0, 21.6, 19.8,
Conclusion
We have developed an efficient approach to five-membered
heterocyclic compounds allenes 2, diphenylvinyl-2,3-dihy-
dro-1H-pyrrole (2y), polycyclic skeletons 3 and 4, and 1,3-
dienyl-2,5-dihydro-1H-pyrrole (6as) by utilizing a Brønsted
acid catalyzed tandem cyclization reaction of hydroxylated
enynes. This Brønsted acid catalyzed domino process in-
volves the formation of an allene carbocation intermediate,
which can be readily trapped by olefins to give various
novel five-membered heterocyclic skeletons. Furthermore,
the simplest, and least expensive, Brønsted acid shows excel-
lent catalytic activity in the reaction with a low catalyst
loading.
19.5 ppm; IR (neat) 2919, 1597, 1348, 1164, 1092, 1033, 818, 664 cmÀ1
;
HRMS (ESI): m/z calcd for C22H23NO2S: 366.1522 [M+H]; found:
366.1520.
General Procedure B: Brønsted acid catalyzed cyclization of hydroxylat-
ed enynes toward five-membered heterocyclic vinylidene 2y: F3CSO3H
(0.00015 mmol, 0.05 mol%) was added to a solution of hydroxylated
enynes 1y (0.30 mmol) in wet CH2Cl2 (3.0 mL) at 08C. Within 5 min,
when the reaction was considered to be complete, as determined by TLC
analysis, the reaction mixture was diluted with ethyl ether (40 mL),
washed with water, saturated brine, dried over Na2SO4, and evaporated
under reduced pressure. The residue was purified by column chromatog-
raphy on silica gel to afford corresponding vinylidenes 2y (28%).
1H NMR (400 MHz, CDCl3): d=7.49 (d, J=8.0 Hz, 2H), 7.42–7.40 (m,
Experimental Section
3H), 7.31 (d, J=8.0 Hz, 2H), 7.26–7.11ACTHNUGRTNENUG(m, 7H), 6.31ACHTUNTGREN(NUGN s, 1H), 5.94 (s, 1H),
4.61 and 4.48 (2ꢁs, 2H), 3.47 (t, J=10.4 Hz, 1H), 3.30 (dd, J=10.4,
5.2 Hz, 1H), 3.18 (dd, J=10.4, 5.6 Hz, 1H), 2.45 (s, 3H), 1.26 (s, 3H);
13C NMR (100 MHz, CDCl3): d=143.8, 143.7, 142.1, 141.6, 140.6, 132.7,
130.2, 129.9, 129.6, 128.7, 128.2, 127.7, 127.6, 127.2, 126.8, 123.5, 119.3,
113.3, 51.9, 51.8, 21.6, 18.6 ppm; IR (neat) 2924, 1711, 1596, 1445, 1356,
General: Column chromatography was carried out on silica gel. Unless
noted, the 1H NMR spectra were recorded at 300 or 400 MHz in CDCl3
and the 13C NMR spectra were recorded at 75 or 100 MHz in CDCl3 with
trimethylsilane (TMS) as an internal standard. IR spectra were recorded
on a FTIR spectrometer, and only the major peaks are reported (in
cmÀ1). Melting points were determined on a microscopic apparatus and
are uncorrected. All new compounds were further characterized by ele-
mental analysis or high-resolution mass spectrometry (HRMS); copies of
their 1H and 13C NMR spectra are provided in the Supporting Informa-
tion. Detailed data of 3aj and 4aj and X-ray crystallographic studies of
1aj are also provided. Commercially available reagents and solvents
were used without further purification. THF was distilled immediately
1165, 1033, 702, 665, 600, 548 cmÀ1
C28H27NO2S: 442.1835 [M+H]; found: 442.1833.
; HRMS (ESI): m/z calcd for
À
À
General procedure C: HSbF6-catalyzed tandem C C and C O formation
toward polycyclic skeletons 3aa–ar and 4aa–ar: HSbF6 (0.015 mmol,
5 mol%) was added to
a solution of hydroxylated enynes 1aa–ar
(0.30 mmol) in wet CH2Cl2 (3.0 mL) at room temperature. When the re-
action was considered to be complete, as determined by TLC analysis,
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Chem. Eur. J. 2011, 17, 305 – 311

Brønsted Acid Catalyzed Cyclization of Hydroxylated Enynes
FULL PAPER
the reaction mixture was diluted with ethyl ether (40 mL), washed with
water, saturated brine, dried over Na2SO4, and evaporated under reduced
pressure. The residue was purified by column chromatography on silica
gel to afford corresponding polycyclic skeletons 3aa–ar and 4aa–ar.
[3] a) L. Zhang, J. Sun, S. A. Kozmin, Adv. Synth. Catal. 2006, 348,
2271; b) V. Michelet, P. Y. Toullec, J. P. GenÞt, Angew. Chem. 2008,
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NfflÇez, A. M. Echavarren, Chem. Rev. 2008, 108, 3326; d) A. S. K.
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Chem. Soc. Rev. 2008, 37, 1766; f) A. S. K. Hashmi, M. Rudolph, J.
Compound 3aa: Reaction time: 2 h; yield: 52%; m.p. 130–1328C;
1H NMR (400 MHz , CDCl3): d=7.54 (d, J=8.4 Hz, 2H), 7.27–7.19 (m,
7H), 3.40 (dd, J=6.4, 2.4 Hz, 1H), 3.05 (q, J=10.4 Hz, 1H), 2.79 (d, J=
10.4 Hz, 1H), 2.57 (d, J=10.4 Hz, 1H), 2.43 (s, 3H), 2.32–2.24 (m, 3H),
2.09–1.95 (m, 3H), 1.68–1.28 (m, 5H), 1.28 (s, 3H), 1.27 ppm (s, 3H);
13C NMR (100 MHz, CDCl3): d=143.4, 140.5, 140.5, 135.4, 132.1, 129.4,
128.3, 127.8, 127.0, 125.5, 99.3, 81.7, 64.4, 62.3, 54.6, 50.1, 47.2, 31.1, 26.0,
25.5, 22.7, 22.6, 21.6, 21.5 ppm; IR (neat): 2927, 1446, 1347, 1161, 1093,
1035, 750, 663, 547 cmÀ1; HRMS (ESI): m/z calcd for C28H33NO3S:
464.2254 [M+H]; found:464.2260.
´
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Compound 4aa: Reaction time: 2 h; yield: 40%; m.p. 99–1018C;
1H NMR (400 MHz, CDCl3): d=7.50 (d, J=8.4 Hz, 2H), 7.27–7.21 (m,
5H), 6.75 (dd, J=7.6, 3.2 Hz, 2H), 4.74 (s, 1H), 3.45 (s, 1H), 3.41 (dd,
J=6.4, 2.0 Hz, 1H), 3.03–2.95 (m, 2H), 2.54 (d, J=10.4 Hz, 1H), 2.44 (s,
3H), 2.33 (dd, J=7.2, 1.6 Hz, 1H), 2.26–2.22 (m, 1H), 2.08–2.04 (m, 1H),
1.73–1.49 (m, 7H), 1.24 (s, 3H), 1.18 ppm (s, 3H); 13C NMR (100 MHz,
CDCl3): d=143.3, 140.0, 139.0, 138.6, 132.0, 129.4, 128.7, 127.9, 127.1,
126.9, 93.6, 83.0, 65.4, 62.7, 61.4, 53.8, 49.5, 31.6, 25.4, 24.8, 23.0, 22.7,
22.6, 21.5 ppm; IR (neat): 2930, 1599, 1451, 1347, 1163, 1040, 817, 737,
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665, 551 cmÀ1
[M+H]; found:464.2260.
; HRMS (ESI): m/z calcd for C28H33NO3S: 464.2254
À
À
General procedure D: HSbF6-catalyzed tandem C C and C O forma-
tion toward 6as: HSbF6 (0.015 mmol, 5 mol%) was added to a solution
of hydroxylated enynes 1as (0.30 mmol) in wet CH2Cl2 (3.0 mL) at room
temperature. When the reaction was considered to be complete, as deter-
mined by TLC analysis, the reaction mixture was diluted with ethyl ether
(40 mL), washed with water, saturated brine, dried over Na2SO4, and
evaporated under reduced pressure. The residue was purified by chroma-
tography on silica gel to afford 6as as a solid (65% yield). Reaction
time: 8 h; m.p. 162–1648C; 1H NMR (400 MHz , CDCl3): d=7.75 (d, J=
8.4 Hz, 2H), 7.39 (d, J=7.2 Hz, 2H), 7.34–7.7.23 (m, 5H), 6.75 (q, J=
15.6 Hz, 1H), 6.60 (d, J=15.6 Hz, 1H), 6.32 (d, J=15.6 Hz, 1H), 6.28 (q,
J=15.6 Hz, 1H), 5.61ACHTUNGTRENNUNG(s, 1H), 4.27 (d, J=3.6 Hz, 2H), 4.21 (d, J=2.8 Hz,
2H), 2.42 ppm (s, 3H); 13C NMR (100 MHz, CDCl3): d=143.5, 137.3,
136.8, 134.2, 134.0, 132.0, 129.8, 128.7, 128.2, 127.9, 127.4, 126.5, 125.2,
123.1, 55.2, 53.7, 21.5 ppm; IR (neat) 3459, 2833, 1595, 1342, 1162, 1107,
989, 811, 753, 669, 544 cmÀ1; HRMS (ESI): m/z calcd for C21H21NO2S:
352.1366 [M+H]; found: 352.1364.
Acknowledgements
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We thank the NSF (NSF-20732002, NSF-20872052 NSF-20090443) and
the Fundamental Research Funds for the Central Universities for finan-
cial support.
[12] The molecular structure of the corresponding product 1aj was deter-
mined by means of X-ray crystallographic studies. CCDC-749617
(3aj) and 749618 (4aj) contain the supplementary crystallographic
data for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via www.ccdc.cam.
ac.uk/data_request/cif.
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Received: August 3, 2010
Published online: November 24, 2010
Chem. Eur. J. 2011, 17, 305 – 311
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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