Notes
J . Org. Chem., Vol. 66, No. 26, 2001 9073
6-pr op-2-yn yloxytetr ah ydr ofu r o[2,3-d][1,3]dioxole (2d), an d
(3aR,5R,6S,6aR)-5-[2-(4-Ben zyloxy-3-m eth oxyph en yl)vin yl]-
6-b u t -2-yn yloxy-2,2-d im et h ylt et r a h yd r ofu r o[2,3-d ][1,3]-
d ioxole (2e). The general method of the Wittig reaction for the
preparation of the above compounds is illustrated by that of 2d .
A 10% aq. NaOH solution (4 mL) was added dropwise with
stirring to a solution of 1b3c (1 g, 0.004 mol), (4-benzyloxy-3-
methoxy)phenylmethyltriphenylphosphonium bromide (4.5 g,
0.008 mol), CH2Cl2 (30 mL), and water (6 mL) at 0 °C. After
addition was over, the mixture was brought to 25 °C and diluted
with water (10 mL). The organic layer was separated, and the
aqueous layer was extracted with CH2Cl2. The combined organic
extracts were washed with water and dried, and removal of
solvent yielded a yellow oil, which on chromatography over silica
gel (EtOAc-petroleum ether) afforded 2d (1.25 g, 65%) as a pale
yellow syrup:
residue was extracted with CH2Cl2. The combined organic
extracts were washed with water and dried, and removal of
solvent gave 2f as a yellow oil (500 mg, 55%), which was used
immediately without purification for the PKR reaction: IR (neat)
2127, 1646 cm-1; [R]25 -6.4 (c 1.1, CHCl3); MS (EI) m/z 209
D
(M+ - 15), 169; H NMR δ 1.31 (s, 3H), 1.48 (s, 3H), 2.59 (d, J
1
) 2.2 Hz, 1H), 3.96 (d, J ) 3.0 Hz, 1H), 4.23 (m, 2H), 4.56 (d, J
) 3.8 Hz, 1H), 4.82 (t, J ) 2.5 Hz,1H), 5.23 (dd, J ) 1.3, 10.4
Hz, 1H), 5.34 (dd, J ) 1.5, 17.2 Hz, 1H), 5.90 (m, 1H), 5.94 (d,
J ) 3.8 Hz, 1H); 13C NMR δ 26.0 (CH3), 26.7 (CH3), 70.5 (CH),
71.7 (CH2), 76.3 (q), 82.3 (CH), 83.9 (CH), 104.6 (CH), 111.9 (q),
117.2 (CH2), 133.8 (CH).
Typ ica l P r oced u r e for P a u son -Kh a n d Rea ction of 2a -
f. The general procedure is illustrated by the preparation of
(5a S,5bR,8a R,9a R,9bR)-7,7-Dim eth yl-1-p h en yl-1,5a ,5b,8a ,-
9a ,9b -h exa h yd r o-4H -5,6,8,9-t et r a oxa cyclop en t a [b]-a s-in -
d a cen -2-on e (3a ).
[R]25 -34.5 (c 2.6, CHCl3); IR (neat) 1646 cm-1; MS (EI) m/z
D
436 (M+), 421 (M+ - 15); H NMR δ 1.30 (s, 3H), 1.42 (s, 3H),
A solution of 2a (50 mg, 0.22 mmol) in dry CH2Cl2 (2 mL)
was added dropwise to a suspension of Co2(CO)8 (81 mg, 0.24
mmol) in dry CH2Cl2 (50 mL) at 25 °C under nitrogen atmo-
sphere. Stirring was continued at the same temperature for 24
h, after which time N-methylmorpholine oxide (150 mg, 1.3
mmol) was added. The mixture was stirred for 30 min and kept
overnight. It was then filtered through a Celite bed, and the
residue was washed repeatedly with CH2Cl2. The combined
filtrate and the washings were evaporated, and the residue was
chromatographed over silica gel (EtOAc-petroleum ether, 1:4)
giving 3a (23 mg, 44%) as a pale yellow oil that solidified on
standing: mp 125-126 °C (EtOAc-petroleum ether, white
1
2.40 (brs,1H), 3.92 (s, 3H), 4.02 (d, J ) 2.7 Hz, 1H), 4.27 (brs,
2H), 4.68 (d, J ) 3.8 Hz, 1H), 5.00 (dd, J ) 2.4, 9.0 Hz, 1H),
5.16 (s, 2H), 5.86 (dd, J ) 9.2, 11.2 Hz, 1H), 5.97 (d, J ) 3.8 Hz,
1H), 6.73-6.84 (m, 3H), 7.07 (s, 1H), 7.26-7.44 (m, 5H); 13C
NMR δ 26.2 (CH3), 26.6 (CH3), 55.9 (CH3), 57.6 (CH2), 70.9 (CH2),
75.1 (q), 75.8 (CH), 79.0 (CH), 82.8 (CH), 82.9 (CH), 104.6 (CH),
111.4 (q), 112.3 (CH), 113.7 (CH), 121.5 (CH), 122.1 (CH), 127.2
(CH), 127.8 (CH), 128.5 (CH), 129.8 (q), 135.5 (CH), 137.0 (q),
147.7 (q), 149.4 (q).
Compounds 2c and 2e were prepared similarly from 1b (1.3
g, 5.8 mmol) and 1c3c (2 g, 8.8 mmol), respectively.
2c: yield (2.12 g, 80%); oil; [R]25 -65.9 (c 2.60, CHCl3); IR
needles); [R]25 +84.6 (c 0.13, CHCl3); MS (EI) m/z 252 (M+),
D
D
(neat) 2117 cm-1; MS (EI) m/z 300 (M+), 285 (M+ - 15); 1H NMR
δ 1.32 (s, 3H), 1.41 (s, 3H), 2.45 (t, J ) 2.1 Hz, 1H), 4.05 (d, J )
3.0 Hz, 1H), 4.26 (d, J ) 2.1 Hz, 1H), 4.67 (d, J ) 3.8 Hz, 1H),
5.03 (dd, J ) 2.8, 8.9 Hz, 1H), 5.91 (dd, J ) 9.2, 11.6 Hz, 1H),
6.81 (d, J ) 11.6 Hz, 1H), 7.34 (m, 5H); 13C NMR δ 26.4 (CH3),
26.6 (CH3), 57.7 (CH2), 75.1 (q), 75.8 (CH), 79.0 (CH), 82.9 (CH),
83.2 (CH), 104.7 (CH), 111.6 (q), 124.2 (CH), 127.6 (CH), 128.2
(CH),128.7 (CH), 135.0 (CH), 136.3 (q).
209 (M+ - 15); IR (KBr) 1698, 1634 cm-1
;
1H NMR δ 1.32 (s,
3H), 1.51 (s, 3H), 2.50 (dd, J ) 6.9, 18.3 Hz, 1H), 2.72 (dd, J )
3.6, 18.3 Hz, 1H), 3.17 (brs, 1H), 4.13 (s, 1H), 4.22 (d, J ) 13.5
Hz, 1H), 4.44 (d, J ) 3.9 Hz, 1H), 4.52 (d, J ) 3.6 Hz, 1H), 4.60
(d, J ) 13.5 Hz, 1H), 5.83 (d, J ) 3.6 Hz, 1H), 6.03 (s, 1H); 13C
NMR (75 MHz, CDCl3) δ 26.0 (CH3), 26.5 (CH3), 37.2 (CH2), 39.4
(CH), 64.8 (CH2), 76.2 (CH), 78.7 (CH), 83.6 (CH), 105.0 (CH),
111.8 (q), 129.3 (CH), 170.1 (q), 207.1 (q). Anal. Calcd for
C13H16O5: C, 61.87; H, 6.39. Found: C, 61.92; H, 6.46.
2e: yield (380 mg, 15%); oil; [R]25 -33.3 (c 0.99, CHCl3); IR
D
(neat) 2223, 1646 cm-1; 1H NMR δ 1.31 (s, 3H), 1.81 (t, J ) 2.0
Hz, 3H), 3.93 (s, 3H), 4.01 (d, J ) 2.9 Hz, 1H), 4.24 (m, 2H),
4.67 (m, 1H), 5.02 (dd, J ) 8.8, 12.6 Hz, 1H), 5.17 (s, 2H), 5.88
(dd, J ) 8.9, 11.6 Hz, 1H), 5.90 (d, J ) 3.8 Hz, 1H), 6.74 (d, J )
11.6 Hz, 1H), 6.84 (m, 2H), 7.07 (d, J ) 1.2 Hz, 1H), 7.28-7.44
(m, 5H); 13C NMR δ 3.6 (CH3), 26.2 (CH3), 26.7 (CH3), 56.0 (CH),
58.3 (CH2), 71.0 (CH2), 74.5 (q), 75.1 (q), 83.0 (CH), 83.1 (CH),
104.7 (CH), 111.4 (q), 111.5 (CH), 112.5 (CH), 121.6 (CH), 122.6
(CH), 127.2 (CH), 127.8 (CH), 128.5 (CH), 130.0 (q), 135.2 (CH),
137.1 (q), 147.7 (q), 149.5 (q).
(3a R,5R,6S,6a R)-6-Allyloxy-5-et h yn yl-2,2-d im et h ylt et -
r a h yd r ofu r o[2,3-d ][1,3]d ioxole (2f). To a suspension of Ph3P
(3.5 g, 13 mmol) and Zn dust (850 mg) in CH2Cl2 (13 mL) cooled
to 0 °C and under a nitrogen atmosphere was added slowly a
solution of CBr4 (4.47 g, 13.5 mmol) in CH2Cl2 (10 mL) from a
syringe. The mixture was stirred at 0 °C for 5 min until the
greenish yellow color of the phosphorus ylide appeared. A
solution of 1c (1.52 g, 6.6 mmol) in CH2Cl2 (10 mL) was then
added to it from a syringe, and the mixture was stirred at 25 °C
for 24 h. Isolation of the dibromide was accomplished by addition
of pentane (40 mL) to the mixture, which was then filtered to
remove insoluble materials. Removal of solvent yielded a dark
yellow syrup, which on chromatography over silica gel (EtOAc-
petroleum ether, 1:9) furnished the corresponding R,R-dibro-
momethylene Wittig product of 1c (1.61 g, 62%) as a light yellow
oil: [R]25D -47.4 (c 1.13, CHCl3); 1H NMR δ 1.32 (s, 3H), 1.51 (s,
3H), 3.98 (d, J ) 2.8 Hz,1H), 3.96 (d, J ) 3.0 Hz, 1H), 4.23 (m,
2H), 4.57 (d, J ) 3.7 Hz, 1H), 4.82 (t, J ) 2.5 Hz, 1H), 5.23 (dd,
J ) 1.3, 10.4 Hz, 1H), 5.34 (dd, J ) 1.5, 17.2 Hz, 1H), 5.92 (m,
1H), 5.94 (d, J ) 3.8 Hz,1H); 13C NMR δ 26.3 (CH3), 26.8 (CH3),
71.3 (CH2), 80.5 (CH), 82.0 (CH), 82.7 (CH), 92.5 (q), 104.7 (CH),
111.9 (q), 117.7 (CH2), 133.6 (CH), 133.7 (CH).
Compounds 2b-f were subjected to the above reaction
maintaining the same conditions to yield 3b-f, respectively.
(1R,5a S,5b R,8a R,9a R,9b R)-1,7,7-Tr im et h yl-1,5a ,5b ,8a ,-
9a ,9b -h exa h yd r o-4H -5,6,8,9-t et r a oxa cyclop en t a [b]-a s-in -
d a cen -2-on e (3b): 35%; mp 131-132 °C (EtOAc-petroleum
ether, white needles); [R]25D +94.9 (c 0.44, CHCl3); IR (KBr) 1706,
1638 cm-1 1H NMR δ 1.23 (d, J ) 7.2 Hz, 3H), 1.32 (s, 3H),
;
1.53 (s, 3H), 2.70 (brs, 1H), 2.73 (m, 1H), 4.12 (s, 1H), 4.22 (d, J
) 13.8 Hz, 1H), 4.48 (d, J ) 2.1 Hz, 1H), 4.52 (d, J ) 3.6 Hz,
1H), 4.60 (d, J ) 13.8 Hz, 1H), 5.84 (d, J ) 3.6 Hz, 1H), 6.00 (s,
1H); 13C NMR δ 13.8 (CH3), 26.1 (CH3), 42.5 (CH), 47.7 (CH),
64.8 (CH2), 75.2 (CH), 78.9 (CH), 83.6 (CH), 105.1 (CH), 111.9
(q), 127.9 (CH), 168.1 (q), 209.4 (q); HRMS calcd for C14H18O5 -
CH3 251.091949, found 251.092631.
(1R ,5a S ,5b R ,8a R ,9a R ,9b R )-7,7-D im e t h y l-1-p h e n y l-
1,5a ,5b,8a ,9a ,9b-h exa h yd r o-4H-5,6,8,9-tetr a oxa cyclop en ta -
[b]-a s-in d a cen -2-on e (3c): yield 87%; mp 132-133 °C (EtOAc-
petroleum ether, white needles); [R]25 +248.8 (c 0.10, CHCl3);
D
IR (KBr) 1701, 1638 cm-1; MS (EI) m/z 328 (M+), 313 (M+
-
15); 1H NMR: δ 1.32 (s, 3H), 1.48 (s, 3H), 3.21 (brs, 1H), 3.90
(d, J ) 3.6 Hz, 1H), 4.12 (s, 1H), 4.29 (d, J ) 13.8 Hz, 1H), 4.47
(brs, 1H), 5.89 (d, J ) 3.6 Hz, 1H), 6.10 (s, 1H), 7.17-7.34 (m,
5H); 13C NMR δ 26.1 (CH3), 26.6 (CH3), 48.7 (CH), 53.8 (CH),
64.6 (CH2), 75.2 (CH), 78.9 (CH), 83.6 (CH), 105.1 (CH), 112.0
(q), 127.2 (CH), 127.8 (CH), 128.3 (CH), 128.9 (CH), 137.9 (q),
168.9 (q), 206.6 (q). Anal. Calcd for C19H20O5: C, 69.49; H, 6.14.
Found: C, 69.92; H, 6.12.
(1R,5a S,5b R,8a R,9a R,9b R)-1-(4-Ben zyloxy-3-m et h oxy-
ph en yl)-7,7-dim eth yl-1,5a,5b,8a,9a,9b-h exah ydr o-4H-5,6,8,9-
tetr a oxa cyclop en ta [b]-a s-in d a cen -2-on e (3d ): yield 93%; mp
140-141 °C (EtOAc-petroleum ether, white microcrystalline
solid); [R]25 +248.6 (c 0.10, CHCl3); MS (EI) m/z 464 (M+), 449
D
A solution of n-BuLi (5.1 mL,1.5 M in hexane) in THF(15 mL)
was added dropwise with stirring to a solution of the above
material in THF (15 mL) at -78 °C dropwise with stirring. After
completion of addition, the reaction mixture was allowed to come
to 25 °C, after which time it was quenched with a saturated
aqueous NH4Cl solution. The mixture was concentrated and the
(M+ - 15), 373 (M+ - 91), 91; IR (KBr) 1710, 1639 cm-1
;
1H
NMR δ 1.32 (s, 3H), 1.48 (s, 3H), 3.16 (brs, 1H), 3.83 (d, J ) 3.9
Hz, 1H), 3.88 (s, 3H), 4.12 (s, 1H), 4.29 (d, J ) 13.8 Hz, 1H),
4.47 (d, J ) 3.6 Hz, 1H), 4.54 (d, J ) 3.6 Hz, 1H), 4.65 (d, J )
13.8 Hz, 1H), 5.13 (s, 2H), 5.88 (d, J ) 3.6 Hz, 1H), 6.08 (s, 1H),
6.64 (dd, J ) 1.5, 9.6 Hz, 1H), 6.71 (d, J ) 1.5 Hz, 1H), 6.84 (d,