A practical total synthesis of (+)-spirolaxine methyl ether

Article abstract of DOI:10.1021/jo1016647

An efficient and practical total synthesis of (+)-spirolaxine methyl ether is described. The phthalide-aldehyde 3 has been prepared via the Diels-Alder reaction between 1,4-unconjugated diene 5 and a long-chain acetylenic dienophile 6. The carbon framework of spiroketal sulfone 4 has been constructed from monobenzyl protected 1,5-pentanediol and the stereochemistry in both the phthalide portion and the spiroketal portion has been established by the Sharpless asymmetric epoxidation.

Full text of DOI:10.1021/jo1016647

pubs.acs.org/joc
infection with this organism is a significant risk factor for
A Practical Total Synthesis of (þ)-Spirolaxine
the development of peptic ulceration4 and adenocarcinoma
of the distal stomach.5 Current treatment of H. pylori infec-
tion involves the prescription of one or more antibiotics in
combination with H2 blockers; however, none of the existing
treatments are capable of complete eradication of H. pylori.6
Spirolaxine 1 and spirolaxine methyl ether 2 (Figure 1) are
produced by various strains of white rot fungi belonging to
the genera Sporotrichum and Phanerochaete.
Methyl Ether
J. S. Yadav,* M. Sreenivas, A. Srinivas Reddy, and
B. V. Subba Reddy
Division of Organic Chemistry, Discovery Laboratory,
Indian Institute of Chemical Technology, Hyderabad, India
yadavpub@iict.res.in
Received September 3, 2010
FIGURE 1. Chemical structure of spirolaxine methyl ether.
These are potent helicobactericidal compounds and useful
for the treatment of gastroduodenal disorders and the pre-
vention of gastric cancer.7 Several structurally related phthal-
ide-containing helicobactericidal compounds that contain a
5,5-spiroacetal moiety have also been reported by Dekker
et al.,8 which also provide promising leads for the treatment
of H. pylori-related diseases.
The spirolaxine and its methyl ether are found to exhibit
cholesterol lowering activity.9a More recent studies have
shown that it has cytotoxic activity toward endothelial cells
(BMEC and Huvec) as well as a variety of tumor cell lines
(LoVo and HL60).9b,c Consequently, there have been some
reports on the total synthesis of spirolaxine methyl ether.10
Due to its fascinating structural features and potent bio-
logical activity, we have attempted the total synthesis of
spirolaxine methyl ether 2. Herein we report an efficient and
practical total synthesis of biologically active polyketide-
derived natural substance, (þ)-spirolaxine methyl ether 2.
An efficient and practical total synthesis of (þ)-spirolaxine
methyl ether is described. The phthalide-aldehyde 3 has
been prepared via the Diels-Alder reaction between 1,4-
unconjugated diene 5 and a long-chain acetylenic dieno-
phile 6. The carbon framework of spiroketal sulfone 4 has
been constructed from monobenzyl protected 1,5-pentanediol
and the stereochemistry in both the phthalide portion and
the spiroketal portion has been established by the Sharp-
less asymmetric epoxidation.
(5) (a) Nomura, A.; Stemmermann, G. N.; Chyou, P. H.; Kato, I.;
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Perez-Perez, G. I.; Blaser, M. J. N. Engl. J. Med. 1991, 325, 1132–1136.
(b) Parsonnet, J.; Friedman, G. D.; Vandersteen, D. P.; Chang, Y.; Vogelman,
J. H.; Orentreich, N.; Sibley, R. K. N. Engl. J. Med. 1991, 325, 1127–1131.
(c) Sipponen, P.; Varis, K.; Fraki, O.; Korri, U. M.; Seppala, K.; Siurala, M.
Scand. J. Gastroenterol. 1990, 25, 966–973. (d) (a) Graham, D. Y.; Lew, G. M.;
Klein, P. D.; Evans, D. G.; Evans, D. J.; Saeed, Z. A.; Malaty, H. M. Ann.
Intern. Med. 1992, 116 (9), 705-708. (e) Hentschel, E.; Brandstatter, G.;
Dragosics, B.; Hirschl, A. M.; Nemec, H.; Schutze, K.; Taufer, M.; Wurzer,
H. N. Engl. J. Med. 1993, 328 (5), 308–312. (f) Marshall, B. J.; Goodwin, C. S.;
Warren, J. R.; Murray, R.; Blincow, E. D.; Blackbourn, S. J.; Phillips, M.;
Waters, T. E.; Sanderson, C. R. Lancet 1988, ii, 1437–1441. (g) Rauws, E. A. J.;
Tytgat, G. N. J. Lancet 1990, 335, 1233–1235.
Helicobacter pylori (H. Pylori) organisms are gram-negative
bacteria that infect the gastric mucosa in 20% to 80% of
the humans throughout the world.1 Prevalence of H. pylori
infection varies depending upon the age and the geographic
location.2a In most of the cases, infection will persist for the
lifetime of an individual without medical intervention.2b In
most infected persons, H. pylori infection is well tolerated
with few or no symptoms over the decades.3 However,
(6) (a) Walsh, J. H.; Peterson, W. L. N. Engl. J. Med. 1995, 333 (15), 984–
991. (b) Rathbone, B. Scrip Magazine 1993, 25.
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chemistry 1990, 29, 613–616. (b) Gaudliana, M. A.; Huang, L. H.; Kaneko,
T.; Watts, P. C. PCT Int. Appl., 1996, W0 9605204; CAN 125:58200.
(8) Dekker, K. A.; Inagake, T.; Gootz, T. D.; Kaneda, K.; Nomura, E.;
Sakakibara, T.; Sakemi, S.; Sugie, Y.; Yamauchi, Y.; Yoshikawa, N.;
Kojima, N. J. J. Antibiot. 1997, 50, 833–839.
(9) (a) Blaser, M. J. Clin. Infect. Dis. 1992, 15, 386–391. (b) Penco, S.;
Pisano, C.; Giannini, G. WO Pat. 01/68070. (c) Deffieu, G.; Baute, R.; Baute,
M. A.; Neven, A. Sci. Ser. D 1979, 288, 647–649.
*To whom correspondence should be addressed. Fax: 91-40-27160512
(1) (a) Blaser, M. J. Clin. Infect. Dis. 1992, 15, 386–391. (b) Taylor, D. N.;
Blaser, M. J. Epidemiol. Rev. 1991, 13, 42–59.
(2) (a) Mackay, J.; Jemal, A.; Lee, N. C.; Parkin, D. M. The Cancer Atlas,
2nd ed.; American Cancer Society: New York, 2006. (b) Stoicov, C.; Saffari,
R.; Cai, X.; Hasyagar, C.; Houghton, J. Gene 2004, 341, 1–17.
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(b) Nannei, R.; Dallavalle, S.; Merlini, L.; Bava, A.; Nasini, G. J. Org. Chem.
2006, 71, 6277–6280. (c) Keaton, K. A.; Phillips, A. J. Org. Lett. 2007, 9, 2717–
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DOI: 10.1021/jo1016647
r
Published on Web 11/08/2010
J. Org. Chem. 2010, 75, 8307–8310 8307
2010 American Chemical Society

Yadav et al.
JOCNote
SCHEME 1. Retrosynthetic Analysis of (þ)-Spirolaxine
SCHEME 2. Synthesis of Phthalide Aldehyde (3)a
Methyl Ether
aReagents and conditions: (a) (i) (COCl)2, DMSO, Et3N, DCM, -78 °C,
89%; (ii) Ph3PdCH;CO2Et, benzene, reflux, 84%; (b) (i) LiAlH4/
AlCl3, Et2O, 0 °C, 89%; (ii) (-)-DIPT, Ti(OiPr)4, TBHP, DCM, -20 °C
91%; (c) TPP, NaHCO3, CCl4, reflux, 93%; (d) Li/naphthalene, liquid
NH3, -78 °C, 88%; (e) tBuMe2Si-Cl, imidazole, DCM, 0 °C to rt 91%;
(f) n-BuLi, ClCO2Me, THF, -78 °C, 86%; (g) 5, neat, N,N-dimethyl-
aniline, 200 °C, 48 h, 45%; (h) (i) TBAF, THF, rt, 6 h, 87%; (ii) Pd/C, H2,
EtOAc, 6 h, 91%; (i) DMP, DCM, 1 h, 84%.
Our retrosynthetic analysis of (þ)-spirolaxine methyl ether is
shown in Scheme 1.
alkyne 16 with n-BuLi followed by addition of methyl chloro-
formate gave a long-chain acetylenic ester 6 in 84% yield.
Subsequently we have attempted the Alder-Rickert reaction
of diene 5 with acetylenic dienophile 6.13 The reaction was
carried out by heating 2:1 ratio of diene 5 and acetylenic
dienophile 6 in a sealed tube at 200 °C in the presence of a
catalytic amount of N,N-dimethylaniline to give the aromatic
precursor 17 in 45% yield. The amount of N,N-dimethyl-
aniline plays a crucial role in the Diels-Alder reaction,
notably the use of a very minute quantity of N,N-dimethyl-
aniline affords the product in higher yield. Surprisingly no
Diels-Alder reaction was observed in the absence of N,N-
dimethylaniline. This cleanly indicates that addition of a
trace amount of N,N-dimethylaniline is essential to facilitate
the reaction. It is noteworthy to mention that 2 equiv of diene
is required to achieve good yields as it is unstable and
susceptible to undergo rearrangement to give the 3-methoxy-
cyclohex-2-enone. Deprotection of silyl ether with TBAF in
THF gave the benzyl-protected phthalide-alcohol, which on
debenzylation followed by oxidation14 with Dess-Martin
periodinane gave the phthalide-aldehyde 3 in 84% yield. The
synthesis of fragment 4 (Scheme 3) began with the known
monobenzyl ether 11, which was oxidized to the corresponding
aldehyde and further homologated by a two-carbon Wittig
olefination to afford R,β-unsaturated ester 19 (E-isomer) as the
sole product.
It was envisioned to proceed via a heterocycle activated
modified Julia-Kocienski olefination10a-d of phthalide-
aldehyde 3 with sulfonyl spiroketal 4. Phthalide-aldehyde 3
was prepared via the Alder-Rickert reaction between 1,4-
unconjugated diene 5 and a long-chain acetylenic dienophile 6,
which in turn was prepared from benzyl-protected
1,4-butanediol 8 by known methods. The stereochemistry
of the sulfonyl spiroketal fragment 4 was derived from
commercially available (R)-3-butyn-2-ol. Sulfonyl spiroke-
tal 4 was prepared via acid-catalyzed cyclization of protected
dihydroxyketone 7, which was synthesized from benzyl-
protected 1,5-pentanediol 11. The phthalide-aldehyde 3
(Scheme 2) was synthesized from a known monobenzyl ether
8, which was oxidized to the corresponding aldehyde and
further homologated by a two-carbon Wittig olefination to
afford R,β-unsaturated ester (E-isomer) 12 as the sole pro-
duct. Reduction of compound 12 with LiAlH4/AlCl3 af-
forded an allylic alcohol in 87% yield, which on Sharpless
asymmetric epoxidation11 with (-)-DIPT, Ti(iPrO)4, and
TBHP at -20 °C furnished epoxy alcohol 13 in 91% yield
with 94% ee (determined by chiral HPLC).
Subsequent reaction of 13 with PPh3 in CCl4 in the
presence of NaHCO3 (10 mol %) at reflux temperature,
followed by base-induced dehydrohalogenation with the
methodology developed by us,12 gave alkynol 15 in 88%
t
overall yield. Treatment of the BuMe2Si-ether protected
Reduction of compound 19 with LiAlH4/AlCl3 afforded
an allylic alcohol in 81% yield, which on Sharpless asymmetric
epoxidation11a-e with (þ)-DIPT, Ti(OiPr)4, and TBHP at -20 °C
(11) (a) Finn, M. G.; Sharpless, K. B. In Asymmetric synthesis; Morrison,
J. D., Ed.; Acadamic Press: New York, 1985; Vol. 5, Chapter 8, p 247.
(b) Pfenninger, A. Synthesis 1986, No. 12, 89–116. (c) Katsuki, T.; Sharpless,
K. B. J. Am. Chem. Soc. 1980, 102, 5974–5976. (d) Gao, Y.; Hanson, R. M.;
Klunder, J. M.; Ko, S. Y.; Masamune, H.; Sharpless, K. B. J. Am. Chem. Soc.
1987, 109, 5765–5780. (e) Yadav, J. S.; Suresh Reddy, Ch. Org. Lett. 2009, 11,
1705–1708.
(13) (a) Birch, A. J.; Mani, N. S.; Subba Rao, G. S. R. J. Chem. Soc.,
Perkin Trans. I 1990, 1423–1427. (b) Kanakum, C. C.; Mani, N. S.;
Ramanathan, H.; Subba Rao, G. S. R. J. Chem. Soc., Perkin Trans. I
1989, 1907–1913.
(12) Yadav, J. S.; Deshpande, P. K.; Sharma, G. V. M. Tetrahedron 1990,
46, 7033–7046.
(14) Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277–7287.
8308 J. Org. Chem. Vol. 75, No. 23, 2010

Yadav et al.
JOCNote
SCHEME 3. Synthesis of Sulfonyl Spiroketal (4)a
SCHEME 4. Synthesis of (þ)-Spirolaxine Methyl Ethera
aReagents and conditions: (a) (i) (COCl)2, DMSO, Et3N, DCM, -78 °C,
86%; (ii) Ph3PdCH;CO2Et, benzene, reflux, 83%; (b) (i) LiAlH4/
AlCl3 Et2O, 0 °C, 81%; (ii) (þ)-DIPT, Ti(OiPr)4, TBHP, DCM, -20 °C,
91%; (c) Red-Al, THF, 88%; (d) tBuMe2Si-Cl, imidazole, DCM, 0 °C
to rt, 90%; (e) (a) Li/naphthalene, THF, -30 °C, 82%; (f) BAIB,
TEMPO, CH3CN:H2O (2:1), 89%; (vii) DCC/CH3CN/Pyr, MeO(H)-
aReagents and conditions:(a) (i) LDA, THF, 0 °C to -30 °C then
Weinreb amide 9 in THF, 88%; (ii) Lindlar catalyst, H2, EtOAc, rt, 92%;
(b) aq HF, CH3CN, 89%; (c) (i) 1-phenyl-1H-tetrazole-5-thiol, PPh3,
DEAD, 62%; (ii) m-CPBA, NaHCO3, DCM, 82%; (d) (a) KHMDS,
THF, -78 °C then aldehyde 3, 75%; (e) PtO2, H2, THF, 6 h, 90%.
NMe HCl, 64%.
3
from monobenzyl-protected 1,5-pentanediol and the phthalide-
aldehyde was prepared from 1,4-butanediol through the Diels-
Alder approach. This synthetic strategy may be applicable to
the synthesis of other complex natural products as well.
furnished epoxy alcohol 20 in 89% yield with 94% ee (deter-
mined by chiral HPLC). Reductive opening of epoxy alcohol 20
with Red-Al afforded diol 21 in good yield.
The diol 21 was protected as silyl ether and then subjected
to debenzylation to give alcohol 23, which on subsequent
oxidation with TEMPO/BAIB gave compound 24. This was
converted into its Weinreb amide 9 by using the Mosset
procedure.15 Treatment of the alkyne 10 with LDA followed
by addition of the Weinreb amide 9 and a subsequent hydro-
genation with the Lindlar catalyst gave the corresponding
Experimental Section
5-({2-[(2R,5R,7R)-2-Methyl-1,6-dioxaspiro[4.5]dec-7-yl]ethyl}-
sulfonyl)-1- phenyl-1H-1,2,3,4-tetraazole (4). To a solution of
thioether 25a (108 mg, 0.309 mmol) in dichloromethane (5 mL) at
0 °C under an atmosphere of nitrogen was added sodium bicarbo-
nate (0.156 g, 1.545 mmol) and a solution of m-chloroperoxy-
benzoic acid (0.106 g, 0.618 mmol) in dichloromethane (5 mL).
After the solution was stirred for 6 h, saturated aqueous sodium
bicarbonate (2 mL) and saturated aqueous sodium thiosulfate
(2 mL) were added. The aqueous layer was extracted with dichloro-
methane (30 mL), and the combined extracts were dried over
Na2SO4. Filtration and removal of the solvent under reduced
pressure provided an oil that was purified by flash column
chromatography, using hexane-ethyl acetate (9:1) as eluent to
t
ketone 7 in excellent yield without affecting BuMe2Si-ether.
Next compound 7 was subjected to tBuMe2Si-ether deprotec-
tion and a subsequent spiroketolization by treatment with
aqueous HF in acetonitrile to give thermodynamically stable
6,5-spiroketal 25 in 84% yield. Conversion of the side chain
alcohol of spiroketal 25 into sulfone 4 proceeded readily in two
steps by treatment with 1-phenyl-1H-tetrazole-5-thiol, PPh3,
and DEAD followed by oxidation with m-CPBA. The key
heterocycle-activated modified Julia olefination was carried out
with phthalide-aldehyde 3 and sulfone 4 (Scheme 4).16
afford the title compound 4 (96 mg, 82%) as a yellow oil: [R]20
D
þ20.6 (c 2.01 in CHCl3); IR (Neat) υ 2932, 2853, 1498, 1342, 1220,
1152, 1066, 984, 763, and 690 cm-1;1H NMR (300 MHz, CDCl3) δ
7.73-7.66 (m, 2H), 7.63-7.58 (m, 3H), 4.15 (sextet, J = 6.6 Hz,
1H), 3.95-3.85 (m, 2H), 3.77-3.67 (m, 1H), 2.16-1.59 (m, 11H),
1.47-1.34 (m, 1H), 1.22 (d, J = 6.0 Hz, 3H); 13C NMR (75 MHz,
CDCl3) δ 153.4, 133.0, 131.4, 129.6, 125.0, 106.2, 74.0, 67.9, 53.0,
37.8, 33.2, 31.3, 30.6, 28.4, 21.1, 19.9; HRMS (ESI) calcd for
C18H25N4O4S [M þ H]þ 393.1596, found 393.1606.
Thus treatment of sulfone 4 with phthalide-aldehyde 3 in
the presence of KHMDS at -78 °C gave the olefin as a
mixture of trans- and cis-isomers, favoring trans-isomer 4a.
Reduction of olefin 4a (trans/cis) with PtO2 under H2 atmo-
sphere gave the target spirolaxinemethyl ether in 72% yield.
The 1H and 13CNMR data and optical rotation of the
synthetic (þ)-spirolaxine methyl ether 2 were in agreement
with data reported in the literature.7,17
In conclusion, we have accomplished the total synthesis
of (þ)-spirolaxine methyl ether through a modified Julia-
Kocienski olefination between spiroketal sulfone and phthalide-
aldehyde. The stereochemistry in both phthalide and spiroketal
portions has been established by the Sharpless asymmetric
epoxidation. The carbon framework of spiroketal was constructed
3-((R)-1,3-Dihydro-5,7-dimethoxy-1-oxoisobenzofuran-3-yl)-
propanal (3). Dess-Martin periodinane (252 mg, 1.0 mmol) was
added to an ice-cooled solution of alcohol 18 (520 mg, 1.2 mmol) in
dichloromethane (10 mL) under nitrogen atmosphere. After being
stirred for 10 min, the reaction mixture was brought to room
temperature and the stirring was continued until the completion of
the reaction (1 h). The reaction mixture was diluted with ether and
the precipitate was filtered off on a pad of Celite, using ether as
solvent, then the filtrate was washed with saturated aq NaHCO3
solution. The combined organic extracts were washed with brine,
dried over Na2SO4, and concentrated under reduced pressure.
The residue was purified by flash column chromatography with
hexane-ethyl acetate (6:4) as a eluent to give the title compound 3
(15) Delamarche, I.; Mosset, P. J. Org. Chem. 1994, 59, 5453–5457.
(16) (a) Brimble, M. A.; Bryant, C. J. Org. Biomol. Chem. 2007, 5, 2858–
2866. (b) Bondar, D.; Paquette, L. A. Org. Lett. 2005, 7, 1813–8116.
(17) Adachi, T.; Takagi, I.; Kondo, K.; Kawashima, A.; Kobayashi, A.;
Taneoka, I.; Morimoto, S.; Hi B. M.; Chen, Z. PCT Int. Appl., 1996, W0
9610020; CAN. 125,86482.
(210 mg, 84%) as viscous liquid: [R]20 þ6.4 (c 1.06, CHCl3);
D
IR (KBr) υ 2930, 2848, 1751, 1724, 1608, 1471, 1341, 1218, 1158,
J. Org. Chem. Vol. 75, No. 23, 2010 8309

Yadav et al.
JOCNote
1040, 983, 839, 753, 687, 556 cm-1; 1H NMR (300 MHz, CDCl3)
δ 9.81 (s, 1H), 6.45 (d, J = 1.7 Hz, 1H), 6.43 (d, J = 1.7 Hz, 1H),
5.36 (dd, J = 3.2, 8.3 Hz, 1H), 3.95 (s, 3H), 3.90 (s, 3H), 2.8-2.7
(m, 1H), 2.65-2.54 (m, 1H), 2.51-2.40 (m, 1H), 1.95-1.83
(m, 1H); 13C NMR (75 MHz, CDCl3) δ 200.7, 166.8, 159.5,
154.2, 106.4, 98.9, 97.3, 78.3, 55.9, 38.7, 26.8; HRMS (ESI) calcd
for C13H14O5Na [M þ Na]þ 273.0738, found 273.0751.
29.6, 27.9, 22.8, 21.1, 20.2; HRMS (ESI) calcd for C24H32-
O6Na (M þ Na)þ 439.2096, found 439.2103.
(þ)-Spirolaxine Methyl Ether (2). Alkene 4a (30 mg, 0.072
mmol) was dissolved in tetrahydrofuran (25 mL) and hydro-
genated by using a hydrogen-filled double balloon in the pre-
sence of platinum(IV) oxide (3 mg) for 6 h. The catalyst was
removed by filtration through a pad of Celite and the solvent
was removed under reduced pressure. Purification of the resul-
tant oil by flash column chromatography with hexane-ethyl
acetate (7:3) as eluent gave the spirolaxine methyl ether 2 (27 mg,
(3R)-5,7-Dimethoxy-3-(E)-5-[(2R,5R,7S)-2-methyl-1, 6-dioxaspiro-
[4.5]dec-7-yl]-3-pentenyl-1,3-dihydro-1-isobenzofuranone (4a). Sul-
fone 4 (70 mg, 0.178 mmol) was dissolved in tetrahydrofuran
(5 mL) and cooled to -78 °C under an atmosphere of argon. To
this stirred solution was added dropwise KHMDS (0.20 mL, 0.5 M
in THF). The resultant deep yellow solution was stirred for 0.75 h
before a solution of aldehyde 3 (89 mg, 0.357 mmol) in tetra-
hydrofuran (3 mL) was added dropwise. After being stirred
at -78 °C for 4 h, the solution was allowed to slowly warm to room
temperature then stirred for 0.75 h. The reaction was quenched by
the addition of brine (3 mL) and the aqueous layer was extracted
with ethyl acetate (3 ꢀ 15 mL). The combined extracts were dried
over Na2SO4 then filtered, and the solvent was removed in vacuo.
The resultant oil was purified by flash column chromatography
with hexane-ethyl acetate (6:4) as eluent to give the title com-
90%) as a yellow oil: [R]20 þ60.7 (c 0.58, CHCl3) [lit.1 þ62
D
(c 0.22, CHCl3)]; IR (KBr) υ 2934, 2861, 1755, 1608, 1461, 1338,
1
1217, 1158, 1053, 1030, 983, 838 cm-1; H NMR (500 MHz,
CDCl3) δ 6.41 (d, 2H, J = 7.8 Hz), 5.30 (dd, 1H, J = 3.4,
7.8 Hz), 4.18-4.11 (m, 1H), 3.95 (s, 3H), 3.89 (s, 3H), 3.64-3.69
(m, 1H), 2.06-2.15 (1H, m), 1.92-1.99 (1H, m), 1.59-1.88
(7H, m), 1.50-1.54 (1H, m), 1.30-1.42 (9H, m), 1.21 (d, 3H, J =
6.2 Hz), 1.14 (dddd, 1H, J = 3.9, 13.1, 13.1, 16.7 Hz); 13C NMR
(75 MHz, CDCl3) δ 168.5, 166.6, 159.5, 155.1, 106.9, 105.9, 98.5,
97.3, 79.8, 73.6, 69.9, 55.9, 55.8, 37.9, 36.0, 34.7, 33.4, 31.3, 30.9,
29.3, 25.4, 24.5, 21.2, 20.3; HRMS (ESI) calcd for C24H34O6Na
(M þ Na)þ 441.2253, found 441.2255. These data were in
agreement with those reported in the literature.12
pound 4a (55 mg, 75%, E-isomer) as a yellow oil: [R]20 þ58.6
D
(c 1.02 in CHCl3); IR (KBr) υ 2928, 2854, 1749, 1607, 1496,
1460, 1339, 1218, 1158, 1057, 1031, and 978 cm-1; 1H NMR
(300 MHz, CDCl3) δ 6.41 (d, 2H, J = 3.9 Hz), 5.56-5.40
(m, 2H), 5.32 (dd, 1H, J = 3.3, 8.6 Hz), 4.18-4.08 (m, 1H),
3.95 (s, 3H), 3.89 (s, 3H), 3.79-3.68 (m, 1H), 2.31-1.93 (m,
5H), 1.90-1.5 (m, 9H), 1.4-1.22 (m, 2H), 1.21 (d, 3H, J =
6.2 Hz); C (75 MHz, CDCl3) δ 168.4, 166.6, 159.5, 155.2,
155.1, 129.9, 128.9, 127.8, 106.1, 98.6, 97.3, 79.2, 78.9, 70.0,
69.9, 55.9, 55.8, 39.4, 38.0,34.8, 34.0, 33.5, 33.4, 31.3, 30.4,
Acknowledgment. M.S. and A.S.R. thank CSIR-New
Delhi for the award of research fellowships.
Supporting Information Available: Experimental procedures,
specific rotation, and spectral data (1H NMR, 13C NMR, IR, MS,
and HRMS) and copies of 1H NMR and 13C NMR spectra for all
compounds described. This material is available free of charge via
the Internet at http://pubs.acs.org.
8310 J. Org. Chem. Vol. 75, No. 23, 2010