A synthetic strategy for polyfunctionalized bicyclo[3.3.1]nonanes based on a tandem three-component [3 + 2] cycloaddition of α-cinnamoyl ketene-S,S-acetals with oxalyl chloride

Article abstract of DOI:10.1021/jo900764s

(Chemical Equation Presented) A simple and highly efficient three-component reaction of the readily available α-cinnamoyl ketene-S,S-acetals 1 with oxalyl chloride has been developed and the corresponding γ- alkylidenebutenolides 2 were obtained stereospe

Full text of DOI:10.1021/jo900764s

pubs.acs.org/joc
their (a) five-carbon 1,5-bielectrophilic nature,3,4 for example,
A Synthetic Strategy for Polyfunctionalized Bicyclo-
[3.3.1]nonanes Based on a Tandem Three-Component
[3 þ 2] Cycloaddition of r-Cinnamoyl Ketene-
S,S-acetals with Oxalyl Chloride
in the regiospecific [5C þ 1C] annulations for the construction
of substituted phenolic ring (Scheme 1, path A),3a (b) dense and
flexible substitution patterns, for example, applicable to the
stereoselective construction of polysubstituted pyrrolizidines
(Scheme 1, path B),5 and (c) good leaving group (alkylthio) that
can be subjected to a nucleophilic vinylic substitution (SNV)
reaction,1,2a-2d,2g for instance, the subsequent displacement of
the remaining alkylthio by an amino group in the [5C þ 1N]
annulations (Scheme 1, path C).4a,4b In this paper, it is shown
that the easily available R-cinnamoyl ketene-S,S-acetals 1 can
be regarded as either a 1,3- binucleophile (R-carbon and
carbonyl oxygen)6 or a C4 1,4-dipole (R- and β0-carbon atoms)
in the reaction of R-cinnamoyl ketene-S,S-acetals 1 with oxalyl
chloride.7 Therefore, the efficient use of the reactive sites5 of
1 provides rapid access to γ-alkylidenebutenolides 2 and poly-
functionalized bicyclo[3.3.1]nonanes 3 (Scheme 1, path D) in
good to high selective manner under mild conditions.
Yu-Long Zhao,* Li Chen, Shao-Chun Yang, Cui Tian, and
Qun Liu*
Department of Chemistry, Northeast Normal University,
Changchun, 130024, People’s Republic of China
zhaoyl351@nenu.edu.cn; liuqun@nenu.edu.cn
Received April 13, 2009
SCHEME 1. Reaction of R-Cinnamoyl Ketene-S,S-acetals
A simple and highly efficient three-component reaction of
the readily available R-cinnamoyl ketene-S,S-acetals 1
with oxalyl chloride has been developed and the corre-
sponding γ-alkylidenebutenolides 2 were obtained stereo-
specifically in excellent yields under very mild conditions.
On the basis of this reaction, a series of highly functiona-
lized bicyclo[3.3.1]nonanes 3 were constructed in good to
high yields in an atom-economic manner with good
In our experiment, at first, a model reaction of R-cinna-
moyl ketene-S,S-acetal 1a with oxalyl chloride was examined
under various reaction conditions (Table 1).8 It was found
that after treatment of 1a (1.0 mmol) with oxalyl chloride
(0.5 mmol) in THF (10 mL) at room temperature for 1 h,
γ-alkylidenebutenolide 2a was produced in 50% yield
(Table 1, entry 1). Whereas when the reaction was performed
at 0 °C for 1.5 h, product 2a was obtained in 70% yield
(Table 1, entry 2). To our satisfaction, the yield of 2a was
increased to 91% when the reaction was carried out at 0 °C in
the presence of triethylamine (1.0 mmol) for 1 h (Table 1,
entry 3). Among the solvents tested, THF seemed to be the
best choice although comparable results were obtained with
dichloromethane as the solvent (Table 1, entry 4). Other
solvents examined, such as DMF and diethyl ether, gave
lower yields (Table 1, entries 5 and 6). In addition, the
reaction of R-cinnamoyl ketene-S,S-acetal 1a with malonyl
chloride was also investigated at 0-25 °C for 8 h under
diastereoselectivity via a BF3 OEt2-mediated novel
tandem double cyclization of γ-alkylidenebutenolides 2
under very mild conditions.
3
Functionalized ketene-S,S-acetals are versatile intermediates
in organic synthesis.1,2 Among them, the easily available
R-cinnamoyl ketene-S,S-acetals 1 have proven to be promising
structural features as novel organic intermediates because of
(1) For reviews, see: (a) Dieter, R. K. Tetrahedron 1986, 42, 3029–3096.
(b) Junjappa, H.; Ila, H.; Asokan, C. V. Tetrahedron 1990, 46, 5423–5506.
(c) Elgemeie, G. H.; Sayed, S. H. Synthesis 2001, 1747–1771.
(2) For selected examples, see: (a) Rao, H. S. P.; Sivakumar, S. J. Org.
Chem. 2006, 71, 8715–8723. (b) Piao, C.-R.; Zhao, Y.-L.; Han, X.-D.; Liu, Q.
J. Org. Chem. 2008, 73, 2264–2269. (c) Chen, L.; Zhao, Y.-L.; Liu, Q.; Chen,
C.; Piao, C.-R. J. Org. Chem. 2007, 72, 9259–9263. (d) Liang, F.; Li, D.;
Zhang, L.; Gao, J.; Liu, Q. Org. Lett. 2007, 9, 4845–4848. (e) Zhao, Y.-L.;
Liu, Q.; Zhang, J.-P.; Liu, Z.-Q. J. Org. Chem. 2005, 70, 6913–6917. (f) Zhao,
Y.-L.; Li, D.-Z.; Han, X.-D.; Chen, L.; Liu, Q. Adv. Synth. Catal. 2008, 350,
1537–1543. (g) Yu, H.; Yu, Z. Angew. Chem., Int. Ed. 2009, 48, 2929–2933.
(3) For selected examples, see: [5C þ 1C] annulations and related
reactions: (a) Bi, X.; Dong, D.; Liu, Q.; Pan, W.; Zhao, L.; Li, B. J. Am.
Chem. Soc. 2005, 127, 4578–4579. (b) Zhang, L.; Liang, F.; Cheng, X.; Liu,
Q. J. Org. Chem. 2009, 74, 899–902. (c) Zhang, Q.; Sun, S.; Hu, J.; Liu, Q.;
Tan, J. J. Org. Chem. 2007, 72, 139–143.
(4) For selected examples, see: [5C þ 1N] annulations: (a) Dong, D.; Bi,
X.; Liu, Q.; Cong, F. Chem. Commun. 2005, 3580–3582. (b) Zhao, L.; Liang,
F.; Bi, X.; Sun, S.; Liu, Q. J. Org. Chem. 2006, 71, 1094–1098. (c) Hu, J.;
Zhang, Q.; Yuan, H.; Liu, Q. J. Org. Chem. 2008, 73, 2442-2445. [5C þ 1S]
annulations: (d) Bi, X.; Dong, D.; Li, Y.; Liu, Q. J. Org. Chem. 2005, 70,
10886–10889.
(5) Tan, J.; Xu, X.; Zhang, L.; Li, Y.; Liu, Q. Angew. Chem., Int. Ed. 2009,
48, 2868–2872.
(6) For a review on the synthesis of butenolides by one-pot cyclization
reactions of silyl enol ethers with oxalyl chloride, see: Langer, P. Synlett
2006, 3369–3381.
(7) Zhang, G.; Huang, X.; Li, G.; Zhang, L. J. Am. Chem. Soc. 2008, 130,
1814–1815.
(8) For C-C bond-forming reactions at the R-position of functionalized
ketene-S,S-acetals with aldehydes, ketones, or unsaturated ketones, see:
(a) Yuan, H.-J.; Wang, M.; Liu, Y.-J.; Liu, Q. Adv. Synth. Catal. 2009,
351, 112–116. (b) Fu, Z.; Wang, M.; Ma, Y.; Liu, Q.; Liu, J. J. Org. Chem.
2008, 73, 7625–7630. (c) Yin, Y.-B.; Wang, M.; Liu, Q.; Hu, J.-L.; Sun, S.-G.;
Kang, J. Tetrahedron Lett. 2005, 46, 4399–4402. (d) Zhang, Q.; Liu, Y.;
Wang, M.; Liu, Q.; Hu, J.; Yin, Y. Synthesis 2006, 3009–3014.
5622 J. Org. Chem. 2009, 74, 5622–5625
Published on Web 06/15/2009
DOI: 10.1021/jo900764s
r
2009 American Chemical Society

Zhao et al.
JOCNote
TABLE 1. Optimization of Reaction Conditions of 1a with Oxalyl
Chloride
TABLE 2. Reactions of R-Alkenoyl Ketene-S,S-acetals 1 with Oxalyl
Chloridea
entry
substrate 1
R
time (h)
2 yield (%)
entry Et3N (equiv)
solvent
T (°C) time (h) 2a yield (%)
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1h
1i
C6H5
4-ClC6H4
4-NO2C6H4
4-FC6H4
4-MeC6H4
4-MeOC6H4
3,4-CH2O2C6H3
2-furanyl
1.0
1.0
2.0
1.5
1.0
1.0
1.0
1.0
2.0
2a (91)
2b (96)
2c (91)
2d (95)
2e (93)
2f (94)
2g (89)
2h (90)
2i (0)
1
2
3
4
5
6
Et3N (0)
Et3N (0)
Et3N (1.0)
Et3N (1.0)
Et3N (1.0)
Et3N (1.0)
THF
THF
THF
CH2Cl2
DMF
(C2H5)2O
25
0
1.0
1.5
1.0
1.0
6.0
6.0
50
70
91
88
20
35
0
0
0
0
(CH3)3
a Reaction conditions: 1 (1.0 mmol), oxalyl chloride (0.5 mmol), Et3N
(1.0 mmol) in THF (10 mL) at 0 °C.
essentially the identical conditions (Table 1, entry 3). How-
ever, no reaction was observed and the R-cinnamoyl ketene-
S,S-acetal 1a was recovered in nearly quantitative yield.
Next, under the optimized conditions (Table 1, entry 3),
the scope of the reaction was investigated and the results are
summarized in Table 2. This reaction shows wide applic-
ability to various aryl groups in R-cinnamoyl ketene-
S,S-acetals 1. For instance, the reaction of the substrates
1a-g with either electron-donating or electron-withdraw-
ing aryl groups successfully afforded the corresponding
γ-alkylidenebutenolides 2a-g in excellent yields (Table 2,
entries 1-7). In the case of 1h with a heteroaryl group, the
reaction also worked well, yielding the desired product 2h in
90% yield (Table 2, entry 8). However, when the substrate 1i
bearing a aliphatic group was treated with oxalyl chloride
under identical conditions, no desired γ-alkylidenebuteno-
lide 2i was obtained (Table 2, entry 9). The structure of 2
was further confirmed by the X-ray diffraction analysis of
2h.9 It should be emphasized that, based on the above
experimental results and the NMR spectra of products 2,
the reaction of R-cinnamoyl ketene-S,S-acetal 1 with oxalyl
chloride proceeds in a highly chemo- and stereospecific
manner.
The reaction of 1 with oxalyl chloride mentioned above
represents a new application of the powerful R-cinnamoyl
ketene-S,S-acetal intermediates.3-5 On the basis of the above
experimental results together with our previous reports3-5,8
and those of others,6,10 a possible mechanism for the formation
of γ-alkylidenebutenolides 2 is proposed (Scheme 2).
Initially, the nucleophilic attack of the R-carbon atom of 1
on a carbonyl carbon of oxalyl chloride generates the
tricarbonyl intermediate A under the reaction conditions as
described (Table 1, either in the presence or absence of TEA),
which is easy to understand because oxalyl chloride is more
SCHEME 2. Proposed Mechanism for the Formation of 2
reactive than an aldehyde or ketone toward nucleophilic
attack.6,8,10 Subsequently, an unstable oxonium intermedi-
ate B appears to be formed by the attack of the carbonyl
oxygen of the cinnamoyl on the carbon atom of the acid
chloride site of intermediate A. Thus, the β0-position of the
cinnamoyl group is more reactive toward a nucleophile and
is attacked by the R-carbon atom of another ketene-
S,S-acetal 1 (intermolecular Michael addition) to give
γ-alkylidenebutenolides 2 in a stereospecific manner due to
steric hindrances. Obviously, the use of triethylamine to
remove HCl from the reaction mixture will increase the yield
and reduce reaction time.
With the consideration that the γ-alkylidenebutenolides 2
possess the structural features of both vinylogous ketene-
S,S-acetals11a and Michael acceptor (β0-carbon atom of the
R-cinnamoyl ketene-S,S-acetal moiety), the cyclization of 2a
as a model reaction in various conditions including catalysts
and solvents via intramolecular Michael addition was in-
vestigated (Table 3).11b As a result, in the presence of BF3
OEt2 (1.0 equiv) the intramolecular cyclization of 2a could
easily proceed to give the bicyclo[3.3.1]nonane 3a in 60%
yield at room temperature for 6 h (Table 3, entry 1). Mean-
3
(9) Crystal data for 2h: C28H30O6S4, red crystal, M = 590.76, triclinic,
˚
˚
˚
P1, a = 8.7052(10) A, b = 9.8540(12) A, c = 18.635(2) A, R = 99.850(2)°, β
3
˚
= 97.480(2)°, γ = 104.845(2)°, V = 1496.8(3) A , Z = 2, T = 293(2), F000
=
620, R1 = 0.0627, wR2 = 0.1419. Crystallographic data have been deposited
with the Cambridge Crystallographic Data Centre (deposition number
CCDC-722177). Copies of the data can be obtained, free of charge, on
application to the director, CCDC 12 Union Road, Cambridge CB2 1EZ,
UK (fax þ44 1223 336033 or e-mail deposit@ccdc.cam.ac.uk).
while, it was proved that a catalytic amount of BF3 OEt2
3
(11) (a) Zhao, Y.-L.; Chen, L.; Liu, Q.; Li, D.-W. Synlett 2007, 37–42.
(b) Yin, Y.; Zhang, Q.; Li, J.; Sun, S.; Liu, Q. Tetrahedron Lett. 2006, 47,
6071–6074.
(10) (a) Langer, P.; Stoll, M. Angew. Chem., Int. Ed. 1999, 38, 1803–1805.
(b) Langer, P.; Schneider, T.; Stoll, M. Chem.;Eur. J. 2000, 6, 3204–3214.
J. Org. Chem. Vol. 74, No. 15, 2009 5623

Zhao et al.
JOCNote
TABLE 3. Acid-Mediated Cyclization of 2a under Different Conditions
TABLE 4. BF3 OEt2-Mediated Cyclization of 2 to Bicycle[3.3.1]non-
3
anes 3a
entry
substrate 2
Ar
C6H5
4-ClC6H4
4-FC6H4
4-MeC6H4
4-MeOC6H4
time (h)
3 yield (%)
drb
entry
catalyst (equiv)
solvent
time (h)
3a yield (%)
1
2
3
4
5
2a
2b
2d
2e
2f
6
7
7
6
6
3a (60)
3b (71)
3d (66)
3e (62)
3f (61)
17:83
15:85
12:88
20:80
20:80
1
2
3
4
5
6
7
8
BF3 OEt2 (1.0)
BF3 OEt2 (0.5)
CH3CN
CH3CN
benzene
THF
6
10
6
6
12
6
60
21
27
13
3
3
BF3 OEt2 (1.0)
BF3 OEt2 (1.0)
3
3
BF3 OEt2 (1.0)
TiCl4 (1.0)
DMF
a Reaction conditions: 2 (1.0 mmol), BF3 OEt2 (1.0 mmol) in CH3CN
3
3
CH3CN
CH3CN
CH3CN
24
15
(8.0 mL) at room temperature. b Diastereomeric ratios were determined
FeCl3 (1.0)
CF3CO2H (1.0)
6
12
by the 1H NMR spectra of 3.
(0.5 equiv) led to lower yield of 3a (21%) together with the
recovery of 2a in 38% yield (Table 3, entry 2).
SCHEME 3. Proposed Mechanism for the Formation of 3
Obviously, the above cyclization reaction provides a
simple and efficient route to polyfunctionalized bicyclo-
[3.3.1]nonane derivatives starting from readily available
acyclic precursors with perfect atom economy involving
an increase in molecular complexity under very mild condi-
tions.12,13 Encouraged by the above results, the scope of the
reaction was examined by selected γ-alkylidenebutenolides 2
under the optimized conditions (Table 3, entry 1); the results
are summarized in Table 4. Clearly, compounds 2 with either
electron-donating or electron-withdrawing groups on the
phenyl ring of the cinnamoyl moiety of 2 could undergo
BF3 OEt2-mediated intramolecular double cyclization effi-
3
for stereoselectivity may be attributed to intramolecular
π-π interaction14 although the steric hindrances may be
responsible.15 The configuration of the main stereoisomer
was finally established by the X-ray diffraction analysis of 3e.16
On the basis of the above experimental results and our
previous reports,11 a possible mechanism for the formation
of bicyclo[3.3.1]nonanes 3 is proposed and depicted in
ciently to give the corresponding polyfunctionalized bicyclo
[3.3.1]nonanes 3 in good to high yields (Table 4, entries 1-5).
In addition, according to 1H and 13C NMR spectra of 3, it
was found that the cyclization reaction proceeds in a regio-
and diastereoselective manner and the two aryl rings in the
main stereoisomer tend to lie coplanar (Table 4, main
1
stereoisomer >80% according to H NMR). The reason
Scheme 3. In the presence of BF3 OEt2, the intramolecular
3
Michael addition of γ-alkylidenebutenolide 2 leads to the
formation of intermediate C with a negative (enolate anion)
and positive charge (carbon cation stabilized by two
ethylthio groups), respectively. Then, bicyclo[3.3.1]nonane
3 could be constructed via subsequent processes, including
cyclization of intermediate C to D and followed by nucleo-
philic attack of the nearby ethylthio sulfur atom at the
carbonyl carbon of the lactone followed by C-O bond
cleavage, C-S bond breaking, and finally C-C double bond
shift.
(12) In general, bicyclic [3.3.1] and [3.2.1] frameworks are accomplished
by reaction of appropriate C3-synthons with cyclic ketones (R,R0-annula-
tion) or, to a lesser extent, with their enamine derivatives (β,β0-annulation).
Designing efficient, short routes for the construction of polycyclic molecules
is currently one of the main challenges in synthetic organic chemistry. For
synthesis and synthetic application of bicyclo[3.3.1]nonanes, see: (a) Peters,
J. A. Synthesis 1979, 321–336. (b) Butkus, E. Synlett 2001, 1827–1835. (c)
Ciochina, R.; Grossman, R. B. Chem. Rev. 2006, 106, 3963–3986.(d)
Barboni, L.; Gabrielli, S.; Palmieri, A.; Femoni, C.; Ballini, R. Chem.;
Eur. J. 2009, Epub ahead of print, DOI 10.1002/chem.200900366. (e) Bhunia,
S.; Wang, K.-C.; Liu, R.-S. Angew. Chem., Int. Ed. 2008, 47, 5063–5066. (f)
Nicolaou, K. C.; Carenzi, G. E. A.; Jeso, V. Angew. Chem., Int. Ed. 2005, 44,
3895–3899. (g) Nuhant, P.; David, M.; Pouplin, T.; Delpech, B.; Marazano,
C. Org. Lett. 2007, 9, 287–289. (h) Itagaki, N.; Sugahara, T.; Iwabuchi, Y.
Org. Lett. 2005, 7, 4181–4183. (i) Rodeschini, V.; Ahmad, N. M.; Simpkins,
N. S. Org. Lett. 2006, 8, 5283–5285. (j) Muthyala, R. S.; Sheng, S.; Carlson,
K. E.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A. J. Med. Chem. 2003,
46, 1589–1602. (k) Takagi, R.; Miwa, Y.; Nerio, T.; Inoue, Y.; Matsumura,
S.; Ohkata, K. Org. Biomol. Chem. 2007, 5, 286–300. (l) Aoyagi, K.;
Nakamura, H.; Yamamoto, Y. J. Org. Chem. 1999, 64, 4148–4151. (m)
Nicolaou, K. C.; Pfefferkorn, J. A.; Kim, S.; Wei, H. X. J. Am. Chem. Soc.
1999, 121, 4724–4725. (n) Geirsson, J. K. F.; Johannesdottir, J. F. J. Org.
Chem. 1996, 61, 7320–7325. (o) Spessard, S. J.; Stoltz, B. M. Org. Lett. 2002,
4, 1943–1946.
(14) (a) Tsuzuki, S.; Uchimaru, T.; Mikami, M. J. Phys. Chem. A 2006,
110, 2027–2033. (b) Mataka, S.; Shigaki, K.; Sawada, T.; Mitoma, Y.;
Taniguchi, M.; Thiemann, T.; Ohga, K.; Egashira, N. Angew. Chem., Int.
Ed. 1998, 37, 2532–2534.
(15) Yang, J.-D.; Kim, M.-S.; Lee, M.; Baik, W.; Koo, S. Synthesis 2000,
801–804.
(16) Crystal data for 3e: C34H38O4S4, yellow crystal, M = 638.88,
˚
˚
˚
monoclinic p2(1)/n, a = 17.519 (4) A, b = 9.4020(19) A, c = 20.893(4) A,
˚
3
R = 90.00°, β = 97.238(4)°, γ = 90.00°, V = 3414.0(12) A , Z = 4, T = 293
(2), F000 = 1352, R1 = 0.1054, wR2 = 0.3049. Crystallographic data have
been deposited with the Cambridge Crystallographic Data Centre (deposi-
tion number CCDC-722176). Copies of the data can be obtained, free of
charge, on application to the director, CCDC 12 Union Road, Cambridge
CB2 1EZ, UK (fax þ44 1223 336033 or e-mail deposit@ccdc.cam.ac.uk).
(13) For a report for the total synthesis of diverse carbogenic complexity
within the resveratrol class from a common building block, see: Snyder, S.
A.; Breazzano, S. P.; Ross, A, G.; Lin, Y.; Zografos, A. L. J. Am. Chem. Soc.
2009, 131, 1753–1765.
5624 J. Org. Chem. Vol. 74, No. 15, 2009

Zhao et al.
JOCNote
In summary, the three-component reaction of the readily
available R-cinnamoyl ketene-S,S-acetals 1 with oxalyl
chloride can proceed in a stereospecific manner under very
mild conditions to give γ-alkylidenebutenolides 2 in excellent
yields. By this reaction, the structural feature that R-cinna-
moyl ketene-S,S-acetals 1 act as either a 1,3-binucleophile or
a C4 1,4-dipole has been recognized. In addition, highly
functionalized bicyclo[3.3.1]nonanes 3 were prepared in
good to high yields in an atom-economic manner with good
1271, 1471, 1633, 1659, 1794, 2960; MS (ESI) m/z 611 [(M þ
1)]þ. Anal. Calcd for C32H34O4S4: C, 62.92; H, 5.61. Found: C,
63.10; H, 5.72
General Procedure for Preparation of 3 (3a as an example). To
a stirred solution of γ-alkylidenebutenolide 2a (1.0 mmol, 610
mg) in CH3CN (8.0 mL) was added BF3 OEt2 (1.0 mmol, 0.13
3
mL) in one portion. Then the reaction mixture was stirred for 6 h
at room temperature. After 2a was consumed (monitored by
TLC), the reaction mixture was poured into water (30 mL) and
extracted with CH2Cl2 (3 ꢀ 10 mL). The combined organic
extracts were dried over anhydrous MgSO4, filtered, and con-
centrated under reduced pressure to yield the corresponding
crude product, which was purified by silica gel chromatography
(diethyl ether/hexane = 1/10, v/v) to give 3a (366 mg, 60%) as a
diastereoselectivity via a BF3 OEt2-mediated novel tandem
double cyclization of γ-alkylidenebutenolides 2 under very
mild conditions. Further studies are in progress.
3
1
yellow crystal. H NMR (CDCl3, 500 MHz) δ 0.84-0.90 (m,
Experimental Section
3H), 1.20-1.28 (m, 3H), 1.29-1.40 (m, 6H), 2.56-2.74 (m, 3H),
2.93-3.09 (m, 3H), 3.37-3.54 (m, 2H), 3.71 (s, 1H), 4.09 (s, 1H),
4.71 (s, 1H), 5.00 (s, 1H), 6.68 (d, J=7.5 Hz, 2H), 6.77-6.79 (m,
3H), 6.90 (t, J=7.5 Hz, 2H), 6.93-6.97 (m, 3H); 13C NMR
(CDCl3, 125 MHz) δ 13.5, 14.4, 14.8, 15.1, 23.2, 26.7, 29.5, 30.4,
44.4, 50.4, 54.2, 54.9, 125.4, 125.6, 126.5 (2C), 127.5 (2C), 127.7
(2C), 127.9, 128.1 (2C), 134.6, 137.1, 140.9, 156.7, 175.3, 188.3,
191.6, 192.6, 196.0; IR (KBr, cm-1) 695, 753, 817, 854, 889,
1081, 1258, 1314, 1370, 1450, 1472, 1655, 2925, 2962; MS(ESI)
m/z 611 [(M þ 1)]þ. Anal. Calcd for C32H34O4S4: C, 62.92; H,
5.61. Found: C, 62.73; H, 5.75.
General Procedure for Preparation of 2 (2a as an example). To
a stirred solution of 1a (1.0 mmol, 278 mg) and triethylamine
(1.0 mmol, 0.14 mL) in THF (10 mL) was added dropwise a
solution of oxalyl chloride (0.5 mmol, 0.043 mL) in THF
(2.0 mL) via a syringe for 5 min at 0 °C. The reaction mixture
was stirred for 1 h at room temperature. After 1a was consumed
(monitored by TLC), the reaction mixture was poured into
water (30 mL), followed by basification with saturated aqueous
NaHCO3 solution to adjust the pH value of the solution to 7,
and extracted with CH2Cl2 (3 ꢀ 10 mL). The combined organic
extracts were dried over anhydrous MgSO4, filtered, and con-
centrated under reduced pressure to yield the corresponding
crude product, which was purified by silica gel chromatography
(diethyl ether/hexane=1/12, v/v) to give 2a (278 mg, 91%) as a
red crystal. Mp 60-62 °C; 1H NMR (CDCl3, 500 MHz) δ: 1.17
(t, J=7.0 Hz, 3H), 1.22-1.29 (m, 9H), 2.68-2.80 (m, 3H), 2.90
(q, J=7.0 Hz, 1H), 3.08-3.09 (m, 4H), 6.11 (d, J=10.5 Hz, 1H),
6.27 (d, J=9.5 Hz, 1H), 6.65 (d, J=16.0 Hz, 1H), 7.12 (d, J=16.0
Hz, 1H), 7.16 (d, J=7.0 Hz, 1H), 7.27 (d, J=7.0 Hz, 3H), 7.30 (d,
J=8.0 Hz, 4H), 7.38 (d, J=8.0 Hz, 2H); 13C NMR (CDCl3, 125
MHz) δ 14.7 (2C), 15.1 (2C), 27.6 (2C), 28.1 (2C), 45.3, 108.1,
117.7, 126.8 (2C), 128.1 (2C), 128.3 (2C), 128.5 (2C), 128.9 (2C),
130.3, 133.9, 134.4, 141.1, 143.4, 143.6, 150.0, 159.0, 169.2,
176.4, 196.1; IR (KBr, cm-1) 774, 866, 990, 1084, 1145, 1222,
Acknowledgment. Financial support from the National
Natural Sciences Foundation of China (20602006), the
Department of Science and Technology of JLSDG
(20080548 and 20082212), and the Training Fund of NE-
NU’S Scientific Innovation Project (NENU-STC07017 and
NENU-STB07007)
Supporting Information Available: Crystallographic data
for 2h (CIF) and 3e (CIF), experimental procedures, NMR spec-
tra, and characterization data for new compounds 2 and 3.
This material is available free of charge via the Internet at
http://pubs.acs.org.
J. Org. Chem. Vol. 74, No. 15, 2009 5625