Preparation of complex bridged bicyclic ring systems from 3,3-diacetoxy-2-phenylsulfonylpropene and β-keto esters

Article abstract of DOI:10.1016/j.tet.2004.12.044

The reaction of beta-keto esters with 3,3-diacetoxy-2-phenylsulfonylpropene affords bicyclic keto esters in good yields.

Full text of DOI:10.1016/j.tet.2004.12.044

Tetrahedron 61 (2005) 2111–2116
Preparation of complex bridged bicyclic ring systems from
3,3-diacetoxy-2-phenylsulfonylpropene and b-keto esters
*
George A. Kraus and Insik Jeon
Department of Chemistry, Iowa State University, 2759 Gilman Hall, Ames, IA 50011, USA
Received 9 September 2004; revised 17 December 2004; accepted 20 December 2004
Available online 15 January 2005
Abstract—The reaction of beta-keto esters with 3,3-diacetoxy-2-phenylsulfonylpropene affords bicyclic keto esters in good yields.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
enone 6 in 55% yield. This reaction involves the
intermediacy of a tribromide. Unfortunately, all attempts
to produce 5b from 4b led only to undesired products
(Scheme 1).
The number of natural products bearing a phloroglucinol
subunit has significantly increased in recent years.1
Berkeleytrione (1) was isolated from Penicillium sp. found
in the Berkeley Pit Lake in Butte, Montana and exhibits
inhibitory activity against matrix metalloproteinase-3 and
caspase-1.2 Preaustinoid A (2) was isolated from Melia
azedarach (Meliaceae) and exhibits broad bacteriostatic
effects.3 Nemorosone (3) was recently isolated and shows
cytotoxic activity against epithelioid carcinoma (HeLa),
epidermoid carcinoma (Hep-2), prostate cancer (PC-3) and
central nervous system cancer (U251).4 As part of a
program to synthesize phloroglucinol-containing natural
products,5 we describe a useful synthesis of bridged bicyclic
compounds.
Michael addition of acrolein to 4c led mainly to recovered
4c plus polymeric products. The use of lower temperatures
and radical inhibitors8 failed to generate a bicyclic
compound. This is in contrast to the successful Michael
addition/intramolecular aldol reaction with acrolein and
carbomethoxy cyclohexanone and is undoubtedly due to the
steric hindrance of the geminal dimethyl group. Padwa has
developed innovative methodology using sulfones as
Michael acceptors.9 We prepared annulation reagent 7
with the idea of performing two successive Michael
additions to form a bridged bicyclic system followed by
reductive elimination of the sulfone to generate a double
bond. The three-step synthesis of 7 began with commer-
cially available 3,3-diacetoxypropene. Addition of phenyl-
sulfenyl chloride followed by oxidation of the sulfide with
2 equiv of MCPBA and elimination using diisopropylethyl-
amine provided sulfone 7 in 80% overall yield on a 50 mmol
scale (Scheme 2).
The Michael addition reaction of 7 was investigated with 4c.
Reaction of 4c with 1 equiv of sodium hydride in THF at
25 8C followed by the addition of sulfone 7 furnished a 71%
isolated yield of adduct 8 as one diastereomer by proton
NMR. The stereochemistry of the methyl group relative to
the quaternary center was not established since the next step
would generate a bicyclic keto ester. Similarly, adducts
9–13 were generated. The E-stereochemistry of beta-
acetoxy sulfone 8 was determined by a NOESY experiment
(Scheme 3).
In a recent report6 we described the preparation of bicyclic
keto ester 5a from 4a by way of the versatile manganese
mediated chemistry developed by Snider.7 Bromination of
5a with 3.5 equiv of NBS led to the isolation of bromo
Keywords: b-Keto esters; Penicillium; Michael addition.
* Corresponding author. Tel.: C1 515 2947794; fax: C1 515 2940105;
e-mail: gakraus@iastate.edu
Cyclization of keto sulfone 8 using 1 equiv of potassium
tert-butoxide at ambient temperature produced three
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.12.044

2112
G. A. Kraus, I. Jeon / Tetrahedron 61 (2005) 2111–2116
Scheme 1.
Cyclization of 9 also suffered from the labile acetoxy group.
Initially, sulfone 9 was converted into tosylate 18 using
potassium tert-butoxide and para-toluenesulfonyl chloride
at 0 8C. Cyclization of 18 with potassium tert-butoxide
afforded divinyl ether 20 in 90% yield. Sulfone 9 was then
converted into pivalate ester 19 and cyclized to 21 (one
diastereomer based on proton NMR) in 57% yield with KH
in THF at 0 8C (Scheme 5).
Scheme 2.
products, esters 14, 15 and 16 in 20, 5 and 50% yields,
respectively. The major product 16 was derived from the
deacetylation of 8. In order to enhance the yield of the
cyclization products, acetate 8 was converted into pivalate
17 with potassium tert-butoxide followed by pivaloyl
chloride at 0 8C in 80% yield. Reaction of 17 with potassium
tert-butoxide in THF from 0 8C to room temperature
afforded a 56% isolated yield of 14, as a 1:0.8 mixture of
hydroxy sulfone diastereomers (Scheme 4).
In view of the problems with acetate 9 and tosylate 18,
sulfones 10 and 11 were transformed directly into the
pivalates and cyclized with potassium hydride in 40 and
83% yields, respectively. Interestingly, the reaction of the
pivalate derived from 11 with potassium hydride gave a
product derived from hydride addition to the enone system
followed by cyclization to pivalate 23, as one diastereomer
based on proton NMR, in 83% yield (Scheme 6).
Scheme 3.
Scheme 4.

G. A. Kraus, I. Jeon / Tetrahedron 61 (2005) 2111–2116
2113
Scheme 5.
2. Experimental
2.1. General
2.1.1. 3,3-Diacetoxy-2-phenylsulfonylpropene (7). To a
mechanically stirred suspension of 6.8 g (0.05 mol) of
N-chlorosuccinimide in 60 mL of dry methylene chloride
at room temperature in a 250 mL flask equipped with a
pressure-equalizing dropping funnel and an efficient con-
denser was added about 0.5 g of a total of 5.5 g (0.05 mol)
of thiophenol. The mixture was then gently heated on a
steam bath for 1–2 min until sulfenyl chloride formation
commenced as evidenced by the intense orange coloration
of the suspension. Once initiated, the remaining thiophenol
was added dropwise at a rate sufficient to maintain the
solvent at reflux. When the addition was complete (usually
about 30 min were required), the homogeneous orange
solution was stirred at room temperature for an additional
30 min. The suspension was then cooled to 0 8C and 8.7 g
(0.055 mol) of 1,1-diacetoxy-2-propene was added in one
portion. The mixture was then maintained at 0 8C until
complete decoloration of the sulfenyl chloride suspension
was observed (2 h). After warming to room temperature, the
colorless suspension was filtered to remove the majority of
the succinimide. Concentration of the combined filtrate and
wash left a pale yellow oil which was diluted with 30 mL of
hexane to precipitate the remainder of the succinimide. This
suspension was let stand 1 h and then filtered, and the filtrate
was evaporated to dryness which was pure enough to be
used without further purification 1H NMR (300 MHz,
CDCl3) 7.53–7.49 (m, 2H), 7.38–7.31 (m, 3H), 7.14
(d, JZ3.6 Hz, 1H), 3.84–3.68 (m, 2H), 3.63–3.58 (m,
1H), 2.09 (s, 3H), 2.08 (s, 3H).
Scheme 6.
Acetoxy sulfone 15, produced from alcohol 14 in 95% yield
by acetylation with acetic anhydride and DMAP in
methylene chloride at 25 8C, can be converted into the
alkene 24 using sodium amalgam in MeOH in 57% yield.10
Product 24 contains the bridgehead methyl group and
bridgehead ester group present in 1 and 2. Interestingly,
pivalate 23 provided only desulfonated product 25 in 80%
yield (Scheme 7).
To a stirred solution of 4.4 g (0.02 mol) of chloro sulfide
prepared above in 25 mL of dry methylene chloride,
cooled to 0 8C under nitrogen, a solution of 2.2 equiv of
m-chloroperbenzoic acid in 50 mL of methylene chloride
was added dropwise. When the addition was complete, the
mixture was stirred an additional 20 min and then filtered to
remove the majority of the chlorobenzoic acid, which was
washed with 30 mL of methylene chloride. The combined
filtrate and wash was diluted with 50 mL of methylene
chloride and then washed successively with 10% NaHCO3
(50 mL), 10% NaHSO3 (50 mL), 10% NaHCO3 again
(50 mL), and saturated brine and finally dried (MgSO4),
which was pure enough to be used without further
purification.
Scheme 7.
In summary, the reaction of diacetoxy sulfone 7 with beta-
keto esters provides a useful synthetic method for the
preparation of complex bicyclic systems. The reactions are
operationally convenient and amenable to scale up to
produce gram quantities of bicyclic compounds.
1H NMR (300 MHz, CDCl3) d 7.98–7.94 (m, 2H),

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G. A. Kraus, I. Jeon / Tetrahedron 61 (2005) 2111–2116
7.76–7.60 (m, 3H), 7.23 (d, JZ3.0 Hz, 1H), 4.17–3.94 (m,
2H), 3.88–3.83 (m, 1H), 2.07 (s, 3H), 2.02 (s, 3H).
171.22, 166.06, 146.92, 144.91, 139.65, 134.81, 133.71,
129.46, 128.30, 124.10, 56.08, 52.81, 30.20, 28.93, 23.67,
20.69, 16.84, 14.34.
A solution of 1.3 mL (7.5 mmol) of diisopropylethylamine
in 50 mL of dry methylene chloride was added dropwise,
under a nitrogen atmosphere, to a stirred solution of 2.3 g
(6.9 mmol) of chlorosulfone at K10 8C. The reaction
temperature was maintained at 0 8C for 2 h, then diluted
with 40 mL of methylene chloride, washed with 25 mL each
of chilled 1 N HCI, water, and brine, and finally dried over
anhydrous magnesium sulfate. Crystallization with diethyl-
ether/hexane gave compound 7 as a white solid, mp
72–73 8C; 1H NMR (300 MHz, CDCl3) d 7.92–7.89
(m, 2H), 7.69–7.54 (m, 3H), 7.39 (s, 1H), 6.75 (s, 1H),
6.36 (s, 1H), 1.96 (s, 6H); 13C NMR (75 MHz, CDCl3) d
167.95, 145.84, 139.68, 134.05, 129.53, 129.43, 128.55,
84.90, 20.61; HRMS (EI) m/z (MKCH3CO2) calcd for
239.03781, found 239.03830.
1
2.2.5. Compound 12. H NMR (300 MHz, CDCl3) d 8.48
(s, 1H), 7.87–7.83 (m, 2H), 7.64–7.51 (m, 3H), 4.19–4.08
(m, 2H), 3.09 (d, JZ15.6 Hz, 1H), 2.63 (d, JZ15.6 Hz,
1H), 2.39–2.30 (m, 2H), 2.22 (s, 3H), 2.03–1.91 (m, 2H),
1.21 (t, JZ6.9 Hz 3H); 13C NMR (75 MHz, CDCl3) d
214.17, 171.14, 166.03, 146.31, 138.85, 133.79, 129.42,
128.49, 124.00, 62.00, 59.04, 37.53, 31.92, 27.70, 20.65,
19.86, 14.11.
1
2.2.6. Compound 13. H NMR (300 MHz, CDCl3) d 8.48
(s, 1H), 7.84–7.81 (m, 2H), 7.63–7.49 (m, 3H), 4.28–4.09
(m, 2H), 3.05 (d, JZ15.6 Hz, 1H), 2.84 (d, JZ15.6 Hz,
1H), 2.61–2.2.45 (m, 2H), 2.20 (s, 3H), 1.33 (s, 3H), 1.27 (t,
JZ7.2 Hz, 3H), 1.06 (t, JZ7.2 Hz, 3H); 13C NMR
(75 MHz, CDCl3) d 207.45, 172.38, 166.02, 146.66,
139.27, 133.68, 129.38, 128.37, 124.22, 61.95, 58.62,
31.64, 28.75, 20.69, 18.64, 14.08, 8.365.
2.2. General procedure for Michael addition to 7
Keto ester (1 mmol) was added dropwise to the solution of
sodium hydride (1 mmol) in THF (10 mL). After 20 min
sulfone 7 (1 mmol) was added in one portion and stirred
for another 1 h. The resulting mixture was neutralized with
AcOH, which was dissolved in 20 mL of ether. The ether
layer was washed with brine and dried over anhydrous
MgSO4. The crude material was purified by column
chromatography.
2.3. Procedure for cyclizations using t-BuOK
To a stirred solution of keto ester (1 mmol) in THF (10 mL)
was added t-BuOK (1 mmol) in one portion at 0 8C.
The mixture was stirred overnight at room temperature
and dissolved in 20 mL of ether. The ether layer was
washed with 10% aq. HCl, brine and dried over anhydrous
MgSO4. The crude material was purified by column
choromatography.
2.2.1. Compound 8. 1H NMR (300 MHz, CDCl3) d 8.29 (d,
JZ3.3 Hz, 1H), 7.88 (d, JZ7.8 Hz, 2H), 7.67–7.52 (m, 3H),
3.67 (s, 3H), 3.31 (d, JZ16.8 Hz, 1H), 2.90 (d, JZ16.8 Hz,
1H), 2.23 (s, 3H), 1.87–1.34 (m, 4H), 0.92 (s, 6H), 0.74 (d,
JZ6.3 Hz, 3H); 13C NMR (75 MHz, CDCl3) d 206.44,
169.59, 166.20, 145.45, 139.58, 133.78, 129.58, 128.27,
123.20, 65.43, 51.43, 42.46, 40.53, 36.20, 30.56, 28.73,
26.28, 25.55, 20.75, 15.27; HRMS (EI) m/z calcd for
436.15558, found 436.15630.
2.3.1. Compound 14. 1H NMR (300 MHz, CDCl3) d 7.95–
7.89 (m, 2H), 7.76–7.54 (m, 3H), 4.52 (d, JZ10.5 Hz, 1H),
3.85 (s, 1H), 3.48 (s, 3H), 3.13–3.03 (m, 1H), 2.05–1.25 (m,
6H), 1.12 (s, 6H), 1.04 (s, 3H), 0.93(s, 3H); 13C NMR
(75 MHz, CDCl3) d 208.94, 170.13, 136.07, 134.92, 129.81,
129.35, 74.31, 66.17, 64.63, 52.29, 51.27, 42.93, 37.81,
29.30, 28.41, 26.48, 25.54, 20.90; HRMS (EI) m/z calcd for
394.14501, found 394.14570.
2.2.2. Compound 9. 1H NMR (300 MHz, CDCl3) d 8.14 (s,
1H), 7.91 (d, JZ7.5 Hz, 2H), 7.64–7.51 (m, 3H), 3.46 (s,
3H), 2.65–2.50 (m, 2H), 2.33–1.21 (m, 6H), 2.02 (s, 3H),
0.91 (s, 3H), 0.72 (s, 3H); 13C NMR (75 MHz, CDCl3) d
207.50, 170.76, 165.72, 142.24, 139.73, 133.47, 129.16,
128.04, 125.55, 66.73, 51.65, 44.17, 39.17, 36.25, 26.72,
26.62, 22.75, 22.53, 20.37; HRMS (EI) m/z calcd for
422.13993, found 422.14080.
2.3.2. Compound 15. 1H NMR (300 MHz, CDCl3) d 7.88–
7.83 (m, 2H), 7.71–7.56 (m, 3H), 5.62 (d, JZ11.4 Hz, 1H),
3.68 (s, 3H), 3.45–3.33 (m, 1H),), 2.76 (dd, JZ14.7, 4.8 Hz,
1H), 2.47 (d, JZ14.4 Hz, 1H), 2.17–1.96 (m, 2H), 1.77–
1.71 (m, 1H), 1.64 (s, 3H), 1.31–1.26 (m, 1H), 1.13 (s, 3H),
1.11 (s, 3H), 0.86 (s, 3H); 13C NMR (75 MHz, CDCl3) d
209.80, 170.86, 169.78, 139.47, 134.07, 129.50, 128.33,
74.83, 62.99, 61.07, 52.31, 49.84, 43.76, 38.08, 33.74,
26.59, 24.58, 22.87, 20.30, 17.63.
1
2.2.3. Compound 10. H NMR (300 MHz, CDCl3) d 8.47
(s, 1H), 7.87–7.83 (m, 2H), 7.63–7.50 (m, 3H), 4.26–4.17
(m, 2H), 2.90–2.76 (m, 2H), 2.52–1.56 (m, 8H), 2.20 (s,
3H), 1.32–1.24 (m, 3H); 13C NMR (75 MHz, CDCl3) d
206.27, 170.67, 165.89, 146.91, 139.82, 133.49, 129.30,
128.07, 124.08, 61.69, 59.98, 40.62, 35.11, 28.89, 27.07,
22.39, 20.59, 13.98; HRMS (EI) m/z calcd for 408.12428,
found 408.12500.
1
2.3.3. Compound 16. H NMR (300 MHz, CDCl3) d 7.88
(m, 2H), 7.62–7.49 (m, 3H), 7.49 (d, JZ1.8 Hz, 1H), 6.88
(d, JZ2.1 Hz, 1H), 3.19 (s, 3H), 2.82–2.61 (m, 2H), 1.82–
1.23 (m, 5H), 1.11–0.89 (m, 9H); 13C NMR (75 MHz,
CDCl3) d 174.63, 152.20, 140.44, 132.87, 129.11, 127.55,
112.56, 105.36, 52.65, 52.22, 38.37, 36.04, 34.54, 27.70,
27.46, 25.60, 24.99, 13.39; HRMS (EI) m/z calcd for
394.14501, found 380.97603.
1
2.2.4. Compound 11. H NMR (300 MHz, CDCl3) d 8.40
(s, 1H), 7.81–7.76 (m, 2H), 7.58–7.43 (m, 3H), 6.57 (br s,
1H), 3.62 (s, 3H), 3.99 (d, JZ15.6 Hz, 1H), 2.75 (d, JZ
15.6 Hz, 1H), 2.45–2.19 (m, 2H), 2.13 (s, 3H), 1.95–1.88
(m, 2H), 1.73 (s, 3H); 13C NMR (75 MHz, CDCl3) d 194.93,
2.3.4. Compound 20. 1H NMR (300 MHz, CDCl3) d 7.88–
7.84 (m, 2H), 7.65–7.52 (m, 3H), 7.46 (d, JZ2.4 Hz, 1H),
5.59 (t, JZ4.2 Hz, 1H), 3.28 (s, 3H), 2.82 (d, JZ15.6 Hz,

G. A. Kraus, I. Jeon / Tetrahedron 61 (2005) 2111–2116
2115
1H), 2.33 (dd, JZ15.6, 2.4 Hz, 1H), 2.17–2.09 (m, 2H),
1.63–1.55 (m, 1H), 1.33–1.28 (m, 1H), 0.98 (s, 3H), 0.85 (s,
3H); 13C NMR (75 MHz, CDCl3) d 171.44, 150.63, 147.13,
140.34, 133.15, 129.22, 127.92, 115.84, 109.73, 52.19,
51.04, 35.47, 33.90, 25.63, 24.23, 20.29; HRMS (EI) m/z
calcd for 362.11880, found 362.11940.
66.63, 51.52, 41.98, 41.23, 39.11, 36.17, 29.92, 27.53,
26.69, 26.26, 25.45, 15.41; HRMS (EI) m/z calcd for
478.20253, found 478.20320.
1
2.5.2. Compound 19. H NMR (300 MHz, CDCl3) d 8.36
(s, 1H), 7.91 (d, JZ7.8 Hz, 2H), 7.64–7.51 (m, 3H), 3.51 (s,
3H), 3.21–3.10 (m, 1H), 2.88 (dd, JZ15.9, 1.2 Hz, 1H),
2.57 (d, JZ15.9 Hz, 1H), 2.38–2.32 (m, 1H), 2.11–2.00 (m,
1H), 1.90–1.67 (m, 2H), 1.34–1.28 (m, 1H), 1.21 (s, 9H),
1.10 (s, 3H), 0.74 (s, 3H); 13C NMR (75 MHz, CDCl3) d
206.40, 174.50, 170.19, 145.62, 140.27, 133.29, 129.10,
128.18, 125.34, 67.25, 51.65, 43.79, 40.02, 39.13, 36.56,
26.74, 24.93, 22.86, 22.49; HRMS (EI) m/z calcd for
464.18688, found 464.18760.
2.4. Procedure for cyclizations using KH
To a stirred solution of potassium hydride (1 mmol) in THF
(10 mL) was added diketone (1 mmol). The mixture was
stirred overnight at room temperature and dissolved in
20 mL of ether. The ether layer was washed with 10% aq.
HCl, brine and dried over anhydrous MgSO4. The crude
material was purified by column choromatography.
2.4.1. Compound 21. 1H NMR (300 MHz, CDCl3) d 7.89–
7.86 (m, 2H), 7.72–7.56 (m, 3H), 5.40 (d, JZ10.8 Hz, 1H),
4.12–4.00 (m, 2H), 3.49–3.39 (m, 1H),), 2.48–1.80 (m, 6H),
1.27–1.21 (m, 1H), 1.15–1.06 (m, 18H); 13C NMR
(75 MHz, CDCl3) d 209.06, 177.39, 170.00, 138.41,
134.41, 129.68, 128.70, 73.82, 62.92, 61.18, 60.78, 54.22,
44.08, 38.71, 33.95, 28.62, 28.44, 27.00, 24.71, 22.73,
14.14; HRMS (EI) m/z calcd for 478.20253, found
478.20310.
2.6. Procedure for tosyl group substitution
To a stirred solution of diketone 9 (422 mg, 1 mmol) in THF
(10 mL) was added t-BuOK (224 mg, 2 mmol) in one
portion at 0 8C. The reaction temperature was maintained at
0 8C for 1 h, then p-toluenesulfonyl chloride (381 mg,
2 mmol) was added. The resulting mixture was neutralized
with AcOH, which was dissolved in 20 mL of ether. The
ether layer was washed with brine and dried over anhydrous
MgSO4. The crude material was purified by column
choromatography.
2.4.2. Compound 22. 1H NMR (300 MHz, CDCl3) d 7.94–
7.89 (m, 2H), 7.73–7.57 (m, 3H), 5.54 (dd, JZ10.5 Hz,
0.9 Hz, 1H), 4.27–4.11 (m, 3H), 3.46–3.36 (m, 1H),
3.01–2.75 (m, 2H), 2.32 (br s, 1H), 2.28–1.51 (m, 6H),
1.18 (t, JZ10.2 Hz 3H), 1.12 (s, 9H); 13C NMR (75 MHz,
CDCl3) d 209.27, 177.41, 171.28, 138.23, 134.44, 129.69,
128.82, 73.26, 61.97, 60.19, 56.39, 55.01, 38.73, 38.06,
34.17, 29.03, 26.99, 17.70, 14.23; HRMS (EI) m/z calcd for
450.17123, found 450.17200.
2.6.1. Compound 18. 1H NMR (300 MHz, CDCl3) d 7.92–
7.39 (m, 10H), 3.49 (s, 3H), 2.49 (s, 3H), 2.09–1.53 (m, 6H),
1.26–1.11 (m, 2H), 0.86 (s, 3H), 0.67 (s, 3H); 13C NMR
(75 MHz, CDCl3) d 207.06, 169.82, 146.56, 143.13, 139.22,
133.60, 131.51, 130.15, 129.14, 128.51, 127.98, 126.70,
66.52, 51.78, 43.93, 38.85, 36.05, 26.50, 26.48, 22.49,
22.42, 21.90; HRMS (EI) m/z calcd for 534.13821, found
534.13900.
2.4.3. Compound 23. Mp 168–169 8C; 1H NMR (300 MHz,
CDCl3) d 7.83 (d, JZ8.4 Hz, 2H), 7.71–7.54 (m, 3H), 5.51
(d, JZ1.5 Hz, 1H), 3.73 (s, 3H), 2.88 (br s, 1H), 2.67 (d, JZ
12.3 Hz, 1H), 2.49 (dd, JZ12.3, 1.8 Hz, 1H), 2.31–1.81 (m,
6H), 1.27 (s, 3H), 0.90 (s, 9H); 13C NMR (75 MHz, CDCl3)
d 207.59, 176.57, 170.40, 136.35, 134.57, 129.64, 129.48,
72.68, 65.73, 58.61, 55.46, 52.67, 39.45, 38.79, 31.21,
28.86, 26.81, 16.53, 15.14; HRMS (EI) m/z calcd for
450.17123, found 450.17190.
2.7. Procedure for aceoxysulfone elimination
The diketone 15 (43.6 mg, 0.1 mmol) in methanol (1 mL)
and ethylacetate (0.5 mL) was stirred at 0 8C with 5%
sodium amalgam. After 3 h, the mixture was poured into
water (5 mL) and extracted with ether three times. The
combined organic layer washed with brine and dried over
anhydrous MgSO4. The crude material was purified by
column choromatography.
2.5. General procedure for pivaloyl group substitution
1
2.7.1. Compound 24. H NMR (300 MHz, CDCl3) d 5.81
To a stirred solution of diketone (1 mmol) in THF (10 mL)
was added t-BuOK (2 mmol) in one portion at 0 8C. The
reaction temperature was maintained at 0 8C for 1 h, then
trimethylacetyl chloride (2 mmol) was added. The resulting
mixture was neutralized with AcOH, which was dissolved in
20 mL of ether. The ether layer was washed with brine and
dried over anhydrous MgSO4. The crude material was
purified by column choromatography.
(dt, JZ9.3, 3.6 Hz, 1H), 5.29 (d, JZ9.3, 1H), 3.71 (s, 3H),
3.13–2.83 (m, 2H), 2.06–1.52 (m, 3H), 1.24–1.167 (m, 1H),
1.11 (s, 3H), 1.09 (s, 6H); 13C NMR (75 MHz, CDCl3) d
210.70, 171.64, 132.74, 127.86, 64.83, 51.86, 46.23, 42.73,
36.89, 36.20, 35.02, 25.46, 25.06, 21.85; HRMS (EI) m/z
calcd for 236.14124, found 236.14170.
1
2.5.1. Compound 17. H NMR (300 MHz, CDCl3) d 8.32
(d, JZ0.9 Hz, 1H), 7.84 (d, JZ8.7 Hz, 2H), 7.62–7.49 (m,
3H), 3.65 (s, 3H), 3.21 (dd, JZ15.6, 0.9 Hz, 1H), 2.99 (d,
JZ15.6 Hz, 1H), 2.04–1.38 (m, 4H), 1.25 (s, 9H), 1.00–0.95
(m, 9H); 13C NMR (75 MHz, CDCl3) d 207.02, 173.77,
170.68, 147.20, 140.17133.47, 129.30, 128.09, 124.61,
Acknowledgements
We thank Iowa State University and the Center for Research
on Botanical Dietary Supplements (NIH grant ES12020) for
partial support of this research.

2116
G. A. Kraus, I. Jeon / Tetrahedron 61 (2005) 2111–2116
Cardenas, J. Phytochemistry 2001, 57, 279–283. Grossman,
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