6606 J . Org. Chem., Vol. 62, No. 19, 1997
Taber and Song
After 10 min, 4-nitrobenzenesulfonyl azide (4.6 g, 20.2 mmol)
was added. After warming to rt for 3 h, the reaction mixture
was partitioned between 0.5 M aqueous phosphate buffer (pH
) 7.0) and CH2Cl2. The combined organic extract was dried
(Na2SO4), concentrated, and chromatographed to give 4 (6.2
g, 63% yield from 19) as a bright yellow oil. TLC Rf (20%
EtOAc/petroleum ether) ) 0.66. 1H NMR (d): 7.33 (m, 5H),
5.31 (m, 1H), 5.10 (m, 2H), 4.54 (s, 2H), 4.16 (dd, J ) 6.8, 11.6
Hz, 1H), 4.02 (dd, J ) 6.8, 11.6 Hz, 1H), 3.75 (s, 3H), 3.67 (m,
1H), 3.54 (d, J ) 5.0 Hz, 2H), 2.5 (m, 2H), 2.11-1.70 (m, 8H0,
1.67 (s, 3H), 1.64 (s, 3H), 1.59 (s, 6H). 13C NMR (d): u 168.0,
140.4, 138.1, 135.2, 131.2, 73.4, 71.4, 66.6, 39.7, 39.6, 26.7, 26.3,
26.2; d 128.3, 127.6, 124.3, 123.8, 120.6, 76.6, 51.8, 25.6, 17.6,
16.4, 15.9. IR (cm-1): 2916, 2088, 1694, 1436, 1341, 1128.
Meth yl (R,R,R)-2-(2,6,10-Tr im eth yl-1(E),5(E),9-tr id ec-
a tr ien yl)-5-[(p h en ylm eth oxy)m eth yl]-2,3,4,5-tetr a h yd r o-
3-fu r a n ca r boxyla te (3a ) a n d Meth yl (R,S,R)-2-(2,6,10-
Tr im et h yl-1(E),5(E),9-t r id eca t r ien yl)-5-[(p h en ylm et h -
oxy)m eth yl]-2,3,4,5-tetr a h yd r o-3-fu r a n ca r boxyla te (3b).
Diazo ester 4 (6.2 g, 13.2 mmol) in a 250 mL round bottom
flask containing a magnetic stir bar was evaporated with
toluene (3 × 20 mL). Methylene chloride was then added by
filtration through a pad of anhydrous K2CO3. Dirhodium
tetraoctanoate (6 mg) was added with stirring. The reaction
was complete in 20 min (TLC analysis). The reaction mixture
was concentrated and the residue was chromatographed to
give 3.41 g of 3a (58% yield from 4) and 1.90 g of 3b (32%
yield from 4).
3a : TLC Rf (20% EtOAc/petroleum ether) ) 0.63. 1H NMR
(d): 7.32 (m, 5H), 5.22 (d, J ) 8.8 Hz, 1H), 5.08 (m, 2H), 4.73
(t, J ) 8.4 Hz, 1H), 4.57 (s, 2H), 4.24 (m, 1H), 3.67 (s, 3H),
3.51 (d, J ) 4.6 Hz, 2H), 2.77 (m, 1H), 2.31 (m, 1H), 2.09-
1.71 (m, 8H), 1.68 (s, 3H), 1.67 (s, 3H), 1.59 (s, 6H). 13C NMR
(d): u 173.7, 141.0, 138.2, 135.2, 131.2, 73.3, 72.2, 39.6, 39.5,
33.0, 26.7, 26.2. IR (cm-1): 2915, 1738, 1455, 1366, 1098. MS
(m/ z): 440 (57), 349 (38), 317 (48), 289 (38), 202 (100). HRMS
calcd for C28H40O4 440.2927, obsd 440.2926. [R] ) +34.5° (c
2.00, CH2Cl2).
3b: TLC Rf (20% EtOAc/petroleum ether) ) 0.56. 1H NMR
(d): 7.35 (m, 5H), 5.16 (d, J ) 8.9 Hz), 1H), 5.09 (m, 2H), 4.87
(t, J ) 8.4 Hz, 1H), 4.58 (dd, J ) 12.2, 21 Hz, 2H), 4.10 (m,
1H), 3.64 (m, 2H), 3.61 (m, 3H), 3.22 (q, J ) 8.2 Hz, 1H), 2.17-
1.71 (m, 11H), 1.68 (s, 3H), 1.67 (s, 3H), 1.60 (s, 3H), 1.58 (s,
3H). 13C NMR (d): u 172.6, 140.6, 138.2, 135.2, 131.2, 73.3,
72.5, 39.6, 31.7, 26.6, 26.5; d 128.2, 127.7, 127.4, 124.2, 123.7,
121.4, 78.1, 77.3, 51.3, 48.1, 25.6, 17.6, 15.9. IR (cm-1): 2919,
1740, 1453, 1169, 1101, 1028. MS (m/ z): 440 (47), 349 (50),
317 (57), 202 (100). HRMS calcd for C28H40O4 440.2927, obsd
440.2909. [R] ) -17.6° (c 2.58, CH2Cl2).
At rt, NaOMe (1 mL, 2.0 M in MeOH) was added to the
minor diastereomer 3b (88 mg, 0.20 mmol) in 1 mL of MeOH.
After 8 h at rt, the reaction was partitioned between ether
and, sequentially, 1 N aqueous HCl, saturated aqueous
NaHCO3, and saturated aqueous NaCl. The combined organic
extract was dried (Na2SO4), concentrated, and chromato-
graphed to give the major diastereomer 3a (68 mg, 88% from
3b) and the minor diastereomer 3b (11 mg).
(S,R,R)-2-(2,6,10-Tr im eth yl-1(E),5(E),9-tr id eca tr ien yl)-
5-[(p h en ylm et h oxy)m et h yl]-2,3,4,5-t et r a h yd r ofu r a n -3-
m eth a n ol (20). LiAlH4 (378 mg, 9.96 mmol) was added to
3a (2.2 g, 5.0 mmol) in 40 mL of dry THF at 0 °C. After 10 h
at rt, water (1.0 mL), aqueous 10% NaOH (1.0 mL), and water
(3.0 mL) were added sequentially over 2 h, at which point the
grayish reaction mixture had become a white paste. The
mixture was filtered with EtOAc, and the filtrate was concen-
trated and chromatographed to give 20 as a colorless oil (96
mg, 84% from 3a ). TLC Rf (40% EtOAc/petroleum ether) )
0.40. 1H NMR (d): 7.33 (m, 5H), 5.22 (d, J ) 8.9 Hz, 1H),
5.09 (m, 2H), 5.56 (s, 2H), 4.35 (t, J ) 8.2 Hz, 1H), 4.16 (m,
1H), 3.59 (m, 2H), 3.49 (m, 2H), 2.12-1.83 (m, 10H), 1.70 (s,
3H), 1.69 (s, 3H), 1.59 (s, 6H). 13C NMR (d): u 140.4, 138.3,
135.3, 131.2, 73.3, 73.0, 63.4, 39.6, 32.0, 26.7, 26.2; d 128.3,
127.6, 127.5, 124.8, 124.3, 123.7, 78.5, 77.1, 47.7, 25.6, 17.6,
16.7, 16.0. IR (cm-1) 2915, 1654, 1540, 1452, 1376, 1098. MS
(m/ z): 412 (48), 351 (12), 325 (31), 243 (61), 203 (100). HRMS
calcd for C27H40O3 412.2977, obsd 412.2957. [R] ) +19.3° (c
2.96, CH2Cl2).
(S,R,R)-2-(2,6,10-Tr im eth yl-1(E),5(E),9-tr id eca tr ien yl)-
3-[(p h en ylsu lfon yl)m eth yl]-5-[(p h en ylm eth oxy)m eth yl]-
2,3,4,5-tetr a h yd r ofu r a n (21). Tosyl chloride (372 mg, 1.95
mmol) was added to a mixture of the primary alcohol 20 (501
mg, 1.22 mmol) and Et3N (493 mg, 4.88 mmol) and DMAP (10
mg) at 0 °C. After 10 h at rt, the mixture was partitioned
between saturated aqueous NaHCO3 and EtOAc. The com-
bined organic extract was dried (Na2SO4) and concentrated.
The residue was chromatographed to give the tosylate as a
colorless oil (640 mg). TLC Rf (20% EtOAc/petroleum ether)
) 0.54.
A mixture of the tosylate (640 mg, 1.12 mmol), Bu4NI (2.1
g, 5.6 mmol), NaSO2Ph (1.2 g, 3.25 mmol), and copper powder
(10 mg) was heated to reflux in 10 mL of THF. Additional
portions of NaSO2Ph (0.4 g) were added after 3 h and after 6
h. After a total of 18 h at reflux, the mixture was cooled and
then partitioned between water and EtOAc. The combined
organic extract was dried (Na2SO4) and concentrated. The
residue was chromatographed to give the sulfone 21 as a
colorless oil (544 mg, 84% from 20). TLC Rf (40% EtOAc/
petroleum ether) ) 0.56. 1H NMR (d): 7.88 (m, 2H), 7.64 (m,
1H), 7.52 (m, 1H), 7.33 (m, 5H), 5.07 (m, 3H), 4.54 (s, 2H),
4.18 (m, 2H), 3.45 (d, J ) 4.8 Hz, 2H), 3.07 (m, 2H), 2.21-
1.84 (m, 10H), 1.68 (s, 3H), 1.65 (s, 3H), 1.60 (s, 3H), 1.58
(s,3H). 13C NMR (d): u 142.9, 139.3, 138.2, 135.4, 131.3, 73.3,
72.7, 58.0, 39.6, 34.3, 26.7, 26.3; d 133.7, 129.3, 128.3, 127.9,
127.6, 127.5, 124.2, 123.6, 122.4, 80.2, 77.2, 39.7, 25.7, 17.7,
16.9. IR (cm-1) 2915, 1448, 1308, 1148, 1086. MS (m/ z): 536
(18), 395 (80), 243 (64), 203 (100). HRMS calcd for C33H44O4S
536.2960, obsd 536.2960. [R] ) +14.7° (c 3.04, CH2Cl2).
(S,R,R)-2-(2,6,10-Tr im et h yl-11-b r om o-1(E),5(E),9(E)-
t r id eca t r ien yl)-3-[(p h en ylsu lfon yl)m et h yl]-5-[(p h en yl-
m eth oxy)m eth yl]-2,3,4,5-tetr a h yd r ofu r a n (22). Selenium
dioxide (1.8 mg) and salicylic acid (11 mg) were dissolved in
0.7 mL of t-butyl hydroperoxide (4.4 M in CH2Cl2). The
resulting solution was added to the sulfone 21 (428 mg, 0.8
mmol) in a 25 °C water bath. After 3 h, the mixture was
partitioned between 10% aqueous NaOH and EtOAc. The
combined organic extract was dried (Na2SO4) and concen-
trated. The residue was chromatographed to give the allylic
alcohol as a colorless oil (174 mg), TLC Rf (30% EtOAc/
petroleum ether) ) 0.22, and recovered sulfone 21 (111 mg).
Triphenylphosphine (203 mg, 0.776 mmol) in 3 mL of CH2Cl2
was added dropwise over 10 min to a solution of the allylic
alcohol (332 mg, 0.6 mmol) and CBr4 (258 mg, 0.776 mmol) in
8 mL of CH2Cl2 at 0 °C. After 2 h at rt, 3 drops of methanol
were added. The reaction mixture was concentrated and
chromatographed to give the allylic bromide 12 as a light
yellow oil (281 mg, 50% yield from 21). TLC Rf (30% EtOAc/
petroleum ether) ) 0.56. 1H NMR (d): 7.86 (m, 2H), 7.63 (m,
1H), 7.52 (m, 1H), 7.32 (m, 5H), 5.57 (m, 1H), 5.04 (m, 1H),
4.54 (s, 2H), 4.15 (m, 2H), 3.96 (s, 2H), 3.45 (d, J ) 4.7 Hz,
2H), 3.07 (m, 2H), 2.28-1.76 (m, 10H), 1.74 (s, 3H), 1.64 (s,
3H), 1.58 (s, 3H). 13C NMR (d): u 142.5, 139.2, 138.1, 134.4,
131.8, 73.2, 72.6, 57.8, 41.7, 39.4, 38.5, 34.1, 26.6, 26.1; d 133.6,
131.0, 129.2, 128.2, 127.7, 127.5, 127.4, 124.1, 122.4, 80.1, 77.1,
39.6, 16.8, 15.8, 14.5. IR (cm-1) 2916, 1447, 1307, 1146, 1086.
MS (m/ z): 534 (20), 395 (68), 345 (18), 303 (33), 243 (100).
HRMS calcd for C33H43O4SBr (M - HBr) 534.2804, obsd
534.2469. [R] ) +15.5° (c 1.10, CH2Cl2).
(1R,14R,16R)-(2E,6E,10E)-16-(Hyd r oxym et h yl)-3,7,11-
tr im eth yl-16-oxabicyclo[12.3.0]h eptadeca-2,6,10-tr ien e (2).
LDA (2.6 mL, 0.2 M) was added to the allylic bromide 22 (230
mg, 0.37 mmol) in 9 mL of dry THF at -78 °C. After 2 h at
-78 °C, the mixture was slowly warmed up to rt over 14 h.
The reaction mixture was partitioned between H2O and EtOAc.
The combined organic extract was dried (Na2SO4), concen-
trated, and chromatographed to give a diastereomeric mixture
of the cyclized compound as a colorless oil (133 mg), TLC Rf
(20% EtOAc/petroleum ether) ) 0.44 and 0.48).
Sodium metal was added to a solution of the sulfone (133
mg, 0.25 mmol) in dry THF and EtOH (6 mL, 1:1 v/v) and
condensed ammonia (15 mL) at -78 °C until the solution was
dark blue. After 10 min at -78 °C, solid NH4Cl was added