910 J. Chin. Chem. Soc., Vol. 48, No. 5, 2001
Chern et al.
turecautiously.Thesolutionwasextractedwithethylacetate
(50 mL 4). The com bined or ganic layer was washed with
sat u rated brine and dried with an hy drous Na2SO4. Af ter fil-
trationandevaporation,anoilyresiduewasobtained.
+8.0 (c 1.0, CH2Cl2); IR (CH2Cl2) cm-1: 2996, 2955, 1733,
1720, 1438, 1293, 1201, 1176; 1H-NMR (CDCl3, 200 MHz)
: 9.60 (1H, d, J = 1.4 Hz), 7.16 (4H, s), 4.88 (1H, t, J = 4.4
Hz), 3.68 (3H, s), 3.00 (2H, dd, J = 8.4 Hz, 7.0 Hz), 2.86~2.47
(6H, m), 1.79~1.40 (4H, m); 13C-NMR (CDCl3, 50 MHz) :
200.5, 173.2, 138.6, 137.2, 129.7, 128.9, 126.7, 126.5, 80.9,
77.1, 62.8, 51.6, 45.0, 37.0, 35.0, 29.2, 27.5, 26.1; MS, m/e
(relativeintensity%):302(M+, 4), 284 (24), 277 (24), 275
(24), 187 (29), 177 (29), 157 (44), 143 (34), 129 (49), 117
(100), 115 (51), 105 (49), 91 (60), 81 (55), 77 (47), 65 (20),
Underargonatmosphereatroomtemperature, theoily
res i due was dis solved in 35 mL of di chloro methane. The re-
ac tion flask was placed into an ice bath. Af ter 10 min utes,
PCC (7.37 g, 34.02 mmol) was added. It was al lowed to stir
for an other 10 min utes be fore the ice bath was re moved. Af-
ter the re ac tion mix ture was stirred at room tem per a ture for
one and a half hours, it was fil tered through a pad of Celite.
The fil trate was con cen trated and the prod uct was pu ri fied
withsilicagelchromatography(EtOAc:n-Hexane=1:2).The
aldehyde 2 3.72 g (72.1% yield) of was ob tained as an oil,
55 (19); HRMS Calcd for C H22O4: 302.15181. Found:
18
302.15181.
Synthesis of (1S,2S,3S,4R)-3-[2-(3-formyl-7-oxabicyclo-
[2,2,1]hept-2-yl-methyl)phenyl]propionic acid methyl
ester 3
[ ]25 +24.1 (c 1.0, CH2Cl2); IR (CH2Cl2) cm-1: 2998, 2955,
D
1734, 1718, 1438, 1268, 1246, 1201, 1175;1H-NMR (CDCl3,
200 MHz) : 9.70 (1H, d, J = 4.2 Hz), 7.18 (4H, s), 4.86 (1H,
d, J= 4.4 Hz), 4.36 (1H, d,J = 4.4 Hz), 3.68 (3H, s), 2.96 (2H,
dd, J = 8.0 Hz, 7.4 Hz), 2.71~2.55 (6H, m), 1.82~1.40 (4H,
m); 13C-NMR (CDCl3, 50 MHz) : 203.0, 173.1, 138.5,
137.9, 129.5, 129.0, 126.8, 78.3, 77.5, 58.8, 51.7, 49.1, 34.8,
32.2, 29.5, 28.9, 27.4; MS, m/e(rel a tive in ten sity %): 302
(M+, 4), 284 (26), 266 (14), 240 (17), 177 (24), 159 (30), 141
(31), 129 (51), 117 (100), 115 (55), 105 (41), 91 (52), 81 (49),
77 (21), 55 (14); HRMS Calcd for C18H22O4: 302.15181.
Found: 302.15190.
Similarly, carbaldehyde 3 was obtained from 2 in
91.2% yield.
25 -7.7 (c 1.0, CH2Cl2).17
[ ]D
Synthesis of (1R,2R,3R,4S)-3-[2-(3-carboxy-7-oxabicyclo-
[2,2,1]hept-2-yl-methyl)phenyl]propionic acid methyl
ester 4
Aldehyde3(1.16 g, 3.84 mmol) was dis solved in 30 mL
ofanhydrousacetone.Underroomtemperatureandargonat-
mo sphere, a cat a lytic amount of 18-crown-6 was added and
stirredfor10minutes. Potassiumpermanganate(0.67g, 4.23
mmol) was added por tion wise over an hour. Af ter the re sult-
ing mix ture was then stirred for an other 2 hours, it was evap o-
rated un der re duced pres sure. The solid was washed with hot
wa ter (20 mL 2) and was fil tered through a pad of Celite.
The fil trate was washed with di chloro methane (60 mL 1)
and the aque ous layer was acid i fied with 2N HCl. Af ter ex-
tractionwithdichloromethane(30mL 5), the com bined or-
ganic layer was washed with sat u rated brine. The or ganic
layer was then dried with an hy drous Na2SO4.Afterfiltration
and evap o ra tion, the oil res i due was pu ri fied by sil ica gel
chromatography(EtOAc:nHexane=1:1). Aslightlyyellow-
ish oil was ob tained in 0.78 g (63.9% yield),[ ]2D6 +35.5 (c
1.0, CHCl3); IR (CH2Cl2) cm-1: 3490, 2998, 2955, 1735,
1710, 1422, 1274, 1176; 1H-NMR (CDCl3, 200 MHz) : 8.65
(1H, bs), 7.17 (4H, s), 4.80 (1H, d, J = 5.2 Hz), 4.32 (1H, d, J
= 3.2 Hz), 3.67 (3H, s), 3.02 (2H, dd, J = 8.4 Hz, 7.6 Hz),
2.80~2.40 (6H, m), 1.71~1.25 (4H, m); 13C-NMR (CDCl3, 50
MHz) : 177.1, 173.4, 138.7, 137.5, 129.8, 129.0, 126.6,
126.4, 80.7, 78.0, 55.0, 51.7, 46.7, 37.3, 35.0, 29.2, 27.5,
25.9; MS, m/e(relativeintensity%):318(M+, 16), 300 (38),
272 (26), 178 (14), 155 (25), 141 (58), 129 (51), 117 (100),
115 (65), 105 (48), 91 (60), 77 (35), 67 (21), 55 (14); HRMS
Synthesis of (1S,2R,3S,4R)-3-[2-(3-formyl-7-oxabicyclo-
[2,2,1]hept-2-yl-methyl)phenyl]propionic acid methyl
ester 2
Similarly,aldehyde 2 was ob tained from 1 in 60%
yield as a light yel low ish oil.[ ]25 -23.8 (c 1.0, CH2Cl2).17
D
Synthesis of (1R,2R,3R,4S)-3-[2-(3-formyl-7-oxabicyclo-
[2,2,1]hept-2-yl-methyl)phenyl]propionic acid methyl
ester 3
Aldehyde2(0.05 g, 0.166 mmol) was dis solved in 1 mL
ofanhydrousMeOH.Themixturewasplacedunderanargon
at mo sphere and the re ac tion flask was placed into an ice bath.
It was stirred for 10 minutes before NaOCH3 (0.0037 g;
0.0068 M in MeOH) was added. The ice bath was re moved af-
ter 10 min utes of stir ring. The mix ture was al lowed to warm
to am bi ent tem per a ture and re acted for 3 hours. One mL of
sat u rated am mo nium chlo ride so lu tion was added, and the
mix ture was ex tracted with EtOAc (2.0 mL 3). The com-
bined or ganic lay ers were washed with sat u rated brine and
dried with an hy drous Na2SO4. Afterfiltrationandevapora-
tion, 0.05 g of the al de hyde was ob tained. (Quan.), [ ]D26