Synthesis of 7-oxa-phomopsolide e and its C-4 epimer

Article abstract of DOI:10.1016/j.tetlet.2003.11.089

A flexible, enantioselective route to highly functionalized α,β-unsaturated δ-lactones has been applied to the synthesis of 7-oxa-phomopsolide E and its C-4 epimer. This approach relies on the application of the Noyori asymmetric hydrogenation of furyl ke

Full text of DOI:10.1016/j.tetlet.2003.11.089

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 1005–1009
Synthesis of 7-oxa-phomopsolide E and its C-4 epimer
Miaosheng Li, Jana Scott and George A. OÕDoherty*
Department of Chemistry, West Virginia University, Morgantown, WV 26506, USA
Received 12 November 2003; accepted 19 November 2003
Abstract—A flexible, enantioselective route to highly functionalized a,b-unsaturated d-lactones has been applied to the synthesis of
7-oxa-phomopsolide E and its C-4 epimer. This approach relies on the application of the Noyori asymmetric hydrogenation of furyl
ketone to produce the secondary furyl alcohol in high enantioexcess, which can be stereoselectively transformed into a,b-unsatu-
rated-d-lactones by a short, highly diastereoselective oxidation and reduction sequence. DCC and Mitsunobu coupling were used to
introduce the side chains of the two natural product analogs.
ꢀ 2003 Elsevier Ltd. All rights reserved.
1. Introduction
O
3
O
The American elm tree thrives in a wide range of soils
OH
and climatic conditions, making it one of the most
widely planted street trees in North America.1 Unfor-
tunately, a completely healthy 100-year-old American
elm can be killed in as little as two weeks if infected with
Dutch elm disease,2 and over 40 million elm trees in the
United States have been killed since the arrival of Dutch
elm disease.3 The fungus responsible for Dutch elm is
spread from tree to tree by the elm bark beetle (Scolytid
beetle).
O
O
1
5
7
9
R
1a: cis, R = O; Phomopsolide A
1b: trans, R = OH; Phomopsolide B
1c: trans, R = O; Phomopsolide C
1d: 6,7-dihydro, R = OH; Phomopsolide D
1e: 6,7-dihydro, R = O; Phomopsolide E
Figure 1. Structures of phomopsolides.
methodology was successfully applied to the synthesis of
phomopsolide C (1c).9 Our approach derives its asym-
metry from (S)-lactic acid and the application of the
Sharpless asymmetric dihydroxylation of vinylfuran.
The resulting secondary furan alcohol is produced in
high enantioexcess and can be stereoselectively trans-
formed into a,b-unsaturated-d-lactones via a short
highly diastereoselective oxidation and reduction
sequence. In our previous synthesis of phomopsolide C
(Scheme 1), a Wittig olefination reaction was used to
introduce the side chain and was further elaborated into
the target structure.
The devastation caused by Dutch elm disease brought
about research to find natural compounds that have
antiboring/antifeeding activity against the elm bark
beetle. As a result, Grove,4 and later Stierle,5 found a
series of related 6-substituted 5,6-dihydro-5-hydroxy-
pyran-2-ones, the phomopsolides (Fig. 1), which possess
the desired deterrent activity for Scolytid beetles as well
as potent antimicrobial activity against Staphylococcus
aureus.
As part of a continuing program directed at the dis-
covery of new antibiotics, we have investigated the
enantioselective syntheses of various biologically
important pyranone natural products both from
dienoates6 and furan alcohols.7;8 In the case of the
phomopsolide class of natural products, our furan
Because of our motivation to test similar compounds as
antibiotics and against Dutch elm disease, we felt that a
related approach to our synthesis could easily generate
structural analogs of the phomopsolide family for bio-
logical testing. To these ends the syntheses of the two
C-4 diastereomers of 7-oxa-phomopsolide E (7a and 7b)
were undertaken. The two targets can easily be envi-
sioned being prepared in a convergent manner from the
* Corresponding author. Fax: +1-304-293-4904; e-mail: george.
oÕdoherty@mail.wvu.edu
0040-4039/$ - see front matter ꢀ 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.11.089

1006
M. Li et al. / Tetrahedron Letters 45 (2004) 1005–1009
alcohol 5 to pyranone 3 (Scheme 4). Treatment of furyl
O
alcohol 5 with NBS13 in aqueous THF (Achmatowicz
reaction),14 gave pyranone 14 in 92% yield. The reaction
of 14 with Jones reagent gave a ketolactone intermedi-
ate, which was taken on without purification to a Luche
reduction15 with NaBH4 and CeCl3 in MeOH, to give
pyranone 3 in 83% yield from 14.
OP
1
O
OP2
OH
O
O
O
O
O
O
2
1c: Phomopsolide C
OH
OTBS
OP2
+
Ph3P
O
O
OTBS
O
OH
OTBS
O
a
O
b
3
4
OH
OTBS
OTBDPS
OTBS
OH
HO
O
O
O
HO
O
3
4
3
5
14
O
5
6
Scheme 4. Reagents and conditions: (a) NBS, NaHCO3, NaOAc,
THF, H2O, 0 ꢁC (92%); (b) Jones reagent, acetone, 0 ꢁC, then NaBH4/
CeCl3, MeOH/CH2Cl2, )78 ꢁC (83%).
Scheme 1. Retrosynthesis of phomopsolide C.
three intermediates pyranone 3, protected lactic acid 6,
and tiglic acid 8 (Scheme 2).
The desired carboxylic acid 6 was synthesized from (S)-
ethyl lactate 15 in two steps and 78% yield. This
sequence involved hydroxyl group protection of 15 with
TBDPSCl to give 16 followed by ester hydrolysis to
form the acid 6 (Scheme 5).
O
O
OH
3, 6, and 8
O
O
O
OH
OTBDPS
OTBDPS
a
b
O
EtO
EtO
HO
7a: C-4 alpha
7b: C-4 beta
O
O
O
OTBDPS
OH
6
+
16
O
+
15
HO
OTBS
O
O
OH
O
Scheme 5. Reagents and conditions: (a) TBDPSCl, DMF, Imid., rt
(95%); (b) KOH, MeOH, rt (82%).
3
6
8
Scheme 2. Retrosynthetic analysis of 7-oxa-phomopsolide D.
The synthesis of 7-oxa-phomopsolide E 7a was then
pursued using a DCC-mediated coupling between pyr-
anone 3 and tiglic acid 8 to yield ester 17a (Scheme 6). A
subsequent TBS-group deprotection using HF gave a
74% yield (two steps) of alcohol 18a. Once again,
resorting to a DCC coupling reaction establishes the
remaining carbons of analog 7a. Thus, a DCC coupling
of 18a with acid 6 resulted in the protected natural
product analog 19a, which was deprotected with HF/Py
(2:1) complex providing 7-oxa-phomopsolide E 7a in
91% yield.
In our previous furan approaches we derived the pyra-
none asymmetry by means of the Sharpless asymmetric
dihydroxylation of vinylfuran.8;10 Because the enantio-
selectivity of the dihydroxylation reaction was less than
perfect,11 we searched for a better asymmetric reaction
and settled on the Noyori reduction of acylfurans. Thus,
the furyl alcohol 5 was enantioselectively prepared from
a Noyori asymmetric hydrogenation of furyl ketone 12,
which occurred in high yield (84%) and ideal enantio-
excess (>96% ee). In turn, the acylfuran 12 could easily
be prepared in three steps from glycolic acid 9 via a
2-lithiofuran addition to the TBS-protected amide 11
(Scheme 3).12
O
O
The synthesis of both 7-oxa-phomopsolide E 7a and its
4-epi isomer 7b began with the conversion of furyl
OH
OTBS
O
O
a
b
OH
OTBS
O
O
O
O
O
O
O
O
O
3
17a
18a
a
c
O
OH
OTBS
OR
b
HO
N
O
O
H
9
12
10 : R =
11 : R = TBS
Ts
N
O
O
Ph
Ph
OH
O
OTBDPS
OH
c
O
Ru
d
d
OTBS
18a
O
OTBS
N
H
O
O
O
O
O
O
13
O
12
5
O
19a
7a
Scheme 3. Reagents and conditions: (a) pyrrolidine, xylene, 150 ꢁC
(83%); (b) TBSCl, DMF, Imid., rt (83%); (c) furan/n-BuLi, THF,
)78 ꢁC (87%); (d) (1S,2S) Noyori catalyst (13), HCO2H/Et3N (1:1)
(84%).
Scheme 6. Reagents and conditions: (a) 8, DCC, DMAP, CH2Cl2
(85%); (b) HF, CH3CN (87%); (c) 6, DCC, DMAP, CH2Cl2 (89%);
(d) HF/Py (2:1), CH3CN (91%).

M. Li et al. / Tetrahedron Letters 45 (2004) 1005–1009
1007
2.2. 1-(20-Furyl)-2-tert-butyldimethylsilanyloxyethan-
1S-ol (5)
O
O
OH
OTBS
O
O
a
b
To a 20 ml flask was added ketone 12 (1.42 g, 5.9 mmol),
formic acid/triethylamine (1:1, 8 ml), CH2Cl2 (3 mL), and
Noyori asymmetric transfer hydrogenation catalyst
OH
OTBS
O
O
O
O
O
O
3
17b
18b
(R)-Ru(g6-mesitylene)-(S,S)-TsDPEN
13
(18 mg,
O
O
0.5 mol %). The resulting solution was stirred at room
temperature for 24 h. The mixture was diluted with water
(20 mL) and extracted with EtOAc (3 · 15 mL). The or-
ganic layers were combined, washed with satd NaHCO3
and brine, dried over Na2SO4, and concentrated under
reduced pressure to afford the crude alcohol. Flash
chromatography (30% EtOAc/hexane) on silica gel yiel-
O
O
OH
OTBDPS
c
d
18b
O
O
O
O
O
O
O
O
19b
7b
Scheme 7. Reagents and conditions: (a) 8, PPh3, DEAD (61%); (b)
HF, CH3CN (82%); (c) 6, DCC, DMAP, CH2Cl2 (86%); (d) HF/Py
(2:1), CH3CN (88%).
ded 1.20 g (5.0 mmol, 84%) of alcohol 5 as a light yellow
25
D
oil: Rf (30% EtOAc/hexane) ¼ 0.54; ½aꢁ )15.4ꢁ (c 1.01,
CH2Cl2); IR (thin film, cmꢀ1) 3447, 2954, 2930, 2884,
1
2857, 1471, 1473, 1361; H NMR (270 MHz, CDCl3) d
The 4-epi isomer of 7a (7b) was similarly prepared
beginning with the esterification of pyranone 3 and tiglic
acid 8 but this time under the Mitsunobu conditions
(Scheme 7).16 Thus simply exposing pyranone 3 and
tiglic acid 8 to a mixture of PPh3 and DEAD gave ester
17b in a 61% yield. Ester 17b was deprotected with HF
to give a 82% yield of alcohol 18b. DCC coupling
between alcohol 18b and acid 6 gave protected 4-epi-7-
oxa-phomopsolide E 19b, and HF/Py (2:1) deprotection
gave the natural product analog 7b in 88% yield.
7.37 (dd, J ¼ 1:7, 0.7 Hz, 1H), 6.34 (dd, J ¼ 3:2, 1.7 Hz,
1H), 6.30 (dd, J ¼ 3:2, 0.7 Hz, 1H), 4.75 (dd, J ¼ 6:4,
4.5 Hz, 1H), 3.85 (dd, J ¼ 10:1, 4.5 Hz, 1H), 3.83 (dd,
J ¼ 10:1, 6.4 Hz, 1H), 2.89 (d, J ¼ 4:2 Hz, 1H), 0.89 (s,
9H), 0.06 (s, 6H); 13C NMR (68 MHz, CDCl3) d 153.6,
142.0, 110.2, 107.0, 68.3, 65.6, 25.8, 18.2, )5.5; calcd for
[C12H22O3Si)H2O]þ: 225.1310, found: 225.1296.
2.3. (5S,6S)-5-(2-Methyl-2-butenoyloxy)-6-(tert-butyldi-
methylsilanyloxymethyl)-5,6-dihydropyran-2-one (17a)
In conclusion, the highly enantio- and diastereocon-
trolled route to the a,b-unsaturated d-lactone natural
products developed in our laboratory was successfully
applied to the syntheses of the natural product analogs
7-oxa-phomopsolide E and its 4-epi isomer, thus dem-
onstrating the flexibility of the method. The synthesis of
both 7a and 7b were completed in only six steps from
furan 5 (10 steps from glycolic acid).
Alcohol 3 (136 mg, 0.53 mmol), tiglic acid (105 mg,
1.05 mmol), dicyclohexylcarbodiimide (217 g, 1.05
mmol), and dimethylaminopyridine (catalytic amount)
were dissolved in 64 ml of CH2Cl2. The reaction mixture
was stirred at room temperature for 5 h. The reaction
mixture was then filtered through a pad of Celite with
excess Et2O and concentrated. The crude product was
purified by silica gel flash chromatography eluting with
10% EtOAc/hexane to yield 152 mg (0.45 mmol, 85%) of
25
D
17a as a clear oil: Rf (30% EtOAc/hexane) ¼ 0.78; ½aꢁ
2. Experimental section
+250ꢁ (c 1.10, CH2Cl2); IR (thin film, cmꢀ1) 2955, 2930,
2857, 1715, 1253, 1134, 1096, 1068, 837; 1H NMR
(500 MHz, CDCl3) d 7.07 (dd, J ¼ 10:0, 6.0 Hz, 1H),
6.86 (dd, J ¼ 14:0, 6.0 Hz, 1H), 6.17 (d, J ¼ 9:5 Hz, 1H),
5.33 (dd, J ¼ 6:0 Hz, 2.5 Hz, 1H), 4.56 (ddd, J ¼ 7:0,
7.0, 2.5 Hz, 1H), 3.88 (d, J ¼ 7:0 Hz, 1H), 1.81–1.76 (m,
6H), 0.83 (s, 9H), 0.01 (d, J ¼ 16:5 Hz, 6H); 13C NMR
(125 MHz, CDCl3) d 166.0, 162.4, 141.0, 139.3, 127.7,
124.9, 78.5, 60.9, 60.2, 25.7, 18.1, 14.5, 12.0, )5.5, )5.6;
CI HRMS calcd for [C17H28O5Si+H]þ: 341.1784, found:
341.1772.
2.1. 1-(20-Furyl)-2-tert-butyldimethylsilanyloxy-
ethanone (12)
A solution of 2-lithiofuran (0.5 M, 26 ml, 13 mmol) was
added dropwise to a solution of amide 11 (2.43 g,
10 mmol) in THF (50 mL) at )78 ꢁC. After stirring for
1 h, the reaction was quenched by addition of satd
NH4Cl (20 mL). It was then diluted with Et2O (200 mL)
and water (100 mL). The organic layer was separated,
washed with brine (50 mL), and dried (Na2SO4). Con-
centration afforded a residue that was purified by flash
chromatography (10% EtOAc/hexane) to give the
desired ketone 12 (2.09, 8.7 mmol, 87%), as a light
yellow oil: Rf (20% EtOAc/hexane) ¼ 0.61; IR (thin film,
cmꢀ1) 2952, 2929, 2856, 1698, 1471, 1255, 1150, 1017,
2.4. (5S,6S)-5-(2-Methyl-2-butenoyloxy)-6-hydroxy-
methyl-5,6-dihydropyran-2-one (18a)
Ester 17a (140 mg, 0.41 mmol), 1 mL of CH3CN, and HF
(5%, 2 ml, ꢂ5.0 mmol) were added to a plastic vial and
stirred at rt for 10 h. The reaction was quenched with
saturated NaHCO3, the aqueous layer was extracted
with EtOAc (2 · 30 mL), and the organic layer was dried
over Na2SO4, and concentrated under reduced pressure
to afford the crude alcohol. Flash chromatography (60%
1
839; H NMR (270 MHz, CDCl3) d 7.58 (dd, J ¼ 1:7,
0.7 Hz, 1H), 7.32 (dd, J ¼ 3:5, 0.7 Hz, 1H), 6.54 (dd,
J ¼ 3:5, 1.7 Hz, 1H), 4.73 (s, 2H), 0.94 (s, 9H), 0.13 (s,
6H); 13C NMR (68 MHz, CDCl3) d 187.0, 150.9, 146.3,
118.0, 112.1, 67.1, 25.8, 18.5, )5.4; CI HRMS calcd for
[C12H20O3Si+Na]þ: 263.1074, found: 263.1076.

1008
M. Li et al. / Tetrahedron Letters 45 (2004) 1005–1009
EtOAc/hexane) on silica gel yielded 81 mg (0.36 mmol,
87%) of alcohol 18a as a colorless oil: Rf (50% EtOAc/
d 174.7, 166.2, 161.5, 140.4, 138.9, 127.0, 124.8, 76.6,
66.6, 62.3, 61.2, 20.0, 14.3, 11.9; ESI HRMS calcd for
[C14H18O7+Na]þ: 321.0950, found: 321.1188.
25
hexane) ¼ 0.23; ½aꢁ +285ꢁ (c 1.02, CH2Cl2); IR (thin
D
film, cmꢀ1) 3446, 2934, 1712, 1649, 1382, 1256, 1131,
1
1066; H NMR (300 MHz, CDCl3) d 7.02 (dd, J ¼ 9:6,
6.0 Hz, 1H), 6.95–6.85 (m, 1H), 6.24 (d, J ¼ 9:6 Hz, 1H),
5.41 (dd, J ¼ 6:0, 2.7 Hz, 1H), 4.64 (ddd, J ¼ 6:5, 6.5,
2.7 Hz, 1H), 3.94 (dd, J ¼ 12:0 Hz, 6.9 Hz, 1H), 3.75 (dd,
J ¼ 12:0 Hz, 6.3 Hz, 1H), 1.82–1.78 (m, 6H); 13C NMR
(75 MHz, CDCl3) d 167.1, 162.3, 140.2, 139.1, 127.1,
125.0, 79.1, 61.9, 60.3, 14.5, 11.9; ESI HRMS calcd for
[C11H14O5+Na]þ: 249.0739, found: 249.0751.
2.7. (5R,6S)-5-(2-Methyl-2-butenoyloxy)-6-(tert-butyldi-
methylsilanyloxymethyl)-5,6-dihydropyran-2-one (17b)
Alcohol 3 (235 mg, 0.91 mmol) was dissolved in 6 mL of
benzene. The solution was cooled to 0 ꢁC and triphe-
nylphosphine (358 mg, 1.37 mmol), tiglic acid (136 mg,
1.36 mmol), and diethyl azodicarboxylate (238 mg,
1.37 mmol) were added to the solution. The solution was
stirred for 12 h, quenched with saturated aqueous
sodium bicarbonate (30 mL), and extracted with EtOAc
(2 · 30 mL). The organic fractions were combined,
washed with brine (30 mL), dried (Na2SO4), and con-
centrated. Purification on silica gel (EtOAc/hexane, 3:7)
2.5. (5S,6S)-5-(2-Methyl-2-butenoyloxy)-6-[(2S)-2-(tert-
butyldiphenylsilanyloxy)propionyloxymethyl]-5,6-dihy-
dro-pyran-2-one (19a)
Alcohol 18a (79 mg, 0.35 mmol), (2S)-(tert-butyldiphe-
nylsilanoxy)propionic acid (228 mg, 0.70 mmol), dicy-
yielded 188 mg (0.55 mmol, 61%) of ester 17b as a col-
25
D
orless oil: Rf (30% EtOAc/hexane) ¼ 0.65; ½aꢁ )155ꢁ (c
clohexylcarbodiimide
(143 mg,
0.70 mmol),
and
1.20, CH2Cl2); IR (thin film, cmꢀ1) 2954, 2932, 2856,
1
dimethylaminopyridine (catalytic amount) were dis-
solved in 8 ml of CH2Cl2. The reaction mixture was
stirred at room temperature for 6 h. The reaction mix-
ture was then filtered through a pad of Celite with Et2O
(40 mL) and concentrated. The crude product was
purified by silica gel flash chromatography eluting with
20% EtOAc/hexane to yield 164 mg (0.31 mmol, 89%) of
1742, 1716, 1651, 1253, 1130, 837; H NMR (270 MHz,
CDCl3) d 6.93 (q, J ¼ 6:9 Hz, 1H), 6.82 (dd, J ¼ 9:9,
3.7 Hz, 1H), 6.10 (dd, J ¼ 9:9, 1.2 Hz, 1H), 5.60 (ddd,
J ¼ 5:2, 4.0, 1.2 Hz, 1H), 4.57 (dd, J ¼ 7:9, 4.0 Hz, 1H),
3.85 (dd, J ¼ 4:2, 1.5 Hz, 2H), 1.83–1.80 (m, 6H), 0.85
(s, 9H), 0.04 (s, 6H); 13C NMR (68 MHz, CDCl3)
d 166.7, 161.9, 142.1, 139.4, 127.6, 122.9, 80.4, 63.4,
62.5, 25.7, 18.2, 14.5, 12.0, )5.6; calcd for
[C30H36O7Si+Na]þ: 559.2123, found: 559.2133.
19a as a colorless oil: Rf (30% EtOAc/hexane) ¼ 0.47;
25
½aꢁ +107ꢁ (c 1.02, CH2Cl2); IR (thin film, cmꢀ1) 3069,
D
2962, 2936, 2860, 1750, 1717, 1651, 1428, 1248, 1135,
1
824; H NMR (270 MHz, CDCl3) d 7.69–7.62 (m, 4H),
7.44 (m, 6H), 6.99 (dd, J ¼ 9:7, 5.7 Hz, 1H), 6.87 (m,
1H), 6.20 (d, J ¼ 9:7 Hz, 1H), 5.03 (dd, J ¼ 5:7, 2.7 Hz,
1H), 4.46 (ddd, J ¼ 6:4, 6.4, 2.7 Hz, 1H), 4.31 (q,
J ¼ 6:7 Hz, 1H), 4.20 (m, 2H), 1.83–1.79 (m, 6H), 1.38
(d, J ¼ 6:7 Hz, 3H), 1.08 (s, 9H); 13C NMR (68 MHz,
CDCl3) d 173.2, 166.3, 161.6, 140.3, 140.0, 135.9, 135.7,
133.2, 133.0, 129.9, 127.7, 127.6, 127.2, 124.8, 75.8, 68.6,
61.5, 61.0, 26.7, 21.2, 19.2, 14.6, 12.0; calcd for
[C30H36O7Si+Na]þ: 559.2123, found: 559.2137.
Acknowledgements
We thank both the Arnold and Mabel Beckman Foun-
dation and the National Institute of General Medical
Sciences (1R01 GM63150-01A1) for their generous
support of this research. Funding for a 600 MHz NMR
by the NSF-EPSCoR (#0314742) is also gratefully
acknowledged.
References and notes
2.6. 7-Oxa-phomopsolide E (7a)
1. Becker, H. Agric. Res. 1996, 44, 4–8.
Ester 19 (153 mg, 0.29 mmol), 2 ml of CH3CN, and HF/
Py (2:1) (2.5 M, 3 mL, ꢂ7.5 mmol) were added to a plastic
vial and stirred at rt for 24 h. The reaction was quenched
with saturated NaHCO3, and the aqueous layer was
extracted with EtOAc (2 · 40 mL). The organic layer was
washed with HCl (1 M, 10 mL), dried over Na2SO4, and
concentrated under reduced pressure to afford the crude
alcohol. Flash chromatography (60% EtOAc/hexane) on
silica gel yielded 78 mg (0.26 mmol, 91%) of 7-oxa-pho-
2. Santamour, F. S.; Bentz, S. E. J. Arboric. 1995, 21, 122–131.
3. Sinclair, W. A.; Lyon, H. H.; Johnson, W. T. In Diseases
of Trees and Shrubs; Cornell University Press: Ithaca, NY,
1987; p 574.
4. Grove, J. F. J. Chem. Soc., Perkin Trans. 1 1985, 865–869.
5. Stierle, D. B.; Stierle, A. A.; Ganser, B. J. Nat. Prod. 1997,
60, 1207–1209.
6. For the synthesis of cryptocarya diacetate and cryptocarya
triacetate, see: (a) Hunter, T. J.; OÕDoherty, G. A. Org.
Lett. 2001, 3, 2777–2780; (b) Smith, C. M.; OÕDoherty, G.
A. Org. Lett. 2003, 5, 1959–1962.
7. Harris, J. M.; OÕDoherty, G. A. Tetrahedron Lett. 2000,
41, 183–187.
mopsolide E 7a as a colorless oil: Rf (50% EtOAc/hex-
25
D
ane) ¼ 0.21; ½aꢁ +243ꢁ (c 1.20, CH2Cl2); IR (thin film,
cmꢀ1) 3468, 2933, 1715, 1648, 1450, 1381, 1254, 1132,
1
1099, 1068; H NMR (300 MHz, CDCl3) d 7.05 (dd,
8. For the application of this approach toward several
styryllactone natural products, see: (a) Harris, J. M.;
OÕDoherty, G. A. Tetrahedron 2001, 57, 5161–5171; (b)
Harris, J. M.; OÕDoherty, G. A. Org. Lett. 2000, 2, 2983–
2986.
J ¼ 9:5, 5.9 Hz, 1H), 6.99–6.87 (m, 1H), 6.27 (d,
J ¼ 9:9 Hz, 1H), 5.40 (dd, J ¼ 5:9, 3.0 Hz, 1H), 4.85
(ddd, J ¼ 6:0, 3.0, 0.9 Hz, 1H), 4.47 (ddd, J ¼ 11:7, 6.0,
6.0, 2H), 4.34 (q, J ¼ 6:9 Hz, 1H), 1.87–1.79 (m, 6H),
1.43 (d, J ¼ 6:9 Hz, 3H); 13C NMR (75 MHz, CDCl3)

M. Li et al. / Tetrahedron Letters 45 (2004) 1005–1009
1009
9. Harris, J. M.; OÕDoherty, G. A. Tetrahedron Lett. 2002,
43, 8195–8199.
10. Harris, J. M.; OÕDoherty, G. A. Tetrahedron Lett. 2000,
41, 183–187.
13. (a) Grapsas, I. K.; Couladouros, E. A.; Georgiadis, M. P.
Polym. J. Chem. 1990, 64, 823–826; (b) Georgiadis, M. P.;
Couladoros, E. A. J. Org. Chem. 1986, 51, 2725–2727.
14. An Achmatowicz reaction is the oxidative rearrangement
of furfuryl alcohols to 2-substituted 6-hydroxy-2H-pyran-
3(6H)-ones, see: (a) Ref. 13, Achmatowicz, O.; Bielski, R.
Carbohydr. Res. 1977, 55, 165–176; (b) For its use in
carbohydrate synthesis, see Ref. 12 and Balachari, D.;
OÕDoherty, G. A. Org. Lett. 2000, 2, 863–866; (c)
Balachari, D.; OÕDoherty, G. A. Org. Lett. 2000, 2,
4033–4036.
11. The Sharpless reaction of vinylfuran occurs with enantio-
excess on the order of 90% and requires a re-crystallization
of the corresponding bis-benzoates to get enantiomerically
pure diol, see: Harris, J. M.; Keranen, M. D.; Nguyen, H.;
Young, V. G.; OÕDoherty, G. A. Carbohydr. Res. 2000,
328, 17–36.
12. For a related procedure using lactic acid, see: (a) Ferrero,
M.; Galobardes, M.; Martin, R.; Montes, T.; Romea, R.;
Rovira, R.; Urpi, F.; Vilarrasa, J. Synthesis 2000, 1608–
1614; (b) Fein, M. L.; Filachione, E. M. J. Am. Chem. Soc.
1953, 75, 2097–2099.
15. Luche, J.-L. J. Am. Chem. Soc. 1978, 110, 2226–2227.
16. Previously we have shown that the Mitsunobu esterifica-
tion reaction works well on pyranone 3, see Ref. 7,
Mitsunobu, O. Synthesis 1981, 1.