Cine Substitution in 2-Oxabicyclo[4.2.0]octanones
J . Org. Chem., Vol. 61, No. 12, 1996 4057
(MNH4+); HRMS calcd for C13H12O3N (M - C3H7NO) 216.0792,
2-P h en yl-4-(p h en ylth io)-3-h ep ten -7-olid e (31): mp 122
°C (CH2Cl2:petroleum ether); 1H NMR δ 7.30 (m, 5H), 5.88 (d,
J ) 6.5 Hz, 1H), 4.68 (d, J ) 6.5 Hz, 1H), 4.51 (m, 2H), 2.48
(m, 2H), 1.93 (m, 2H); 13C NMR δ 174.8 (s), 136.8, 136.6 (s),
123., 129.3, 128.7, 128.6, 127.8, 127.6 (d), 67.9 (t), 51.7 (d),
29.1 (t), 28.2 (t); IR (neat) 1730, 1610 cm-1; MS CI m/e 311
(MH+), 283 (MH+ - CO), 201 (M - PhSH); HRMS calcd for
C19H18O2S 310.10256, found 310.10263.
found 216.0786.
Rea ction of 5 w ith Na N3. Treatment of 0.2 g (0.85 mmol)
of 5 with 110 mg (2 equiv) of NaN3 and 0.1 g of LiClO4 in 10
mL of acetone for 0.5 h gave in 70% overall yield a mixture of
three products 19 in a ratio of 4:1:2.1 The products were
separated by chromatography (eluent 1:4 to 1:1 EtOAc:
hexane).
(Z)- an d (E)-Meth yl 7-h ydr oxy-2-ph en yl-4-(ph en ylth io)-
3-h ep ten oa te (29 a n d 30). This mixture was obtained as
an oil: 1H NMR δ 7.30 (m, 10H)*, 6.37 (dt, J ) 10, 0.5 Hz,
1H), 6.22 (d, J ) 11 Hz, 1H), 5.13 (d, J ) 10 Hz, 1H), 4.70 (d,
J ) 10 Hz, 1H), 3.68 (s, 3H)*, 3.54 (t, J ) 7 Hz, 2H), 3.52 (t,
J ) 7 Hz, 2H), 2.33 (m, 2H)*, 1.7 (m, 2H)* absorbance of the
two isomers; 13C NMR δ 173.5 (s), 172.9 (s), 138.6, 138.0, 136.4,
133.8 (s), 132.6, 131.6, 130.4, 130.1, 129.1, 129.0, 128.9, 127.9,
127.8, 127.4, 127.3, 126.7, 61.7 (t), 61.3 (t), 52.4 (q), 52.3 (q),
51.8 (d), 50.9 (d), 33.4 (t), 31.1 (t), 30.9 (t), 27.4 (t); IR (neat)
1730 cm-1; MS CI m/e 343 (MH+, 10), 311 (MH+ - MeOH, 5),
283 (MH+ - CO2Me, 100), 325 (MH+ - H2O, 23). Anal. Calcd
for C20H22O3S: C, 70.16; H, 6.48. Found: C, 69.87; H, 6.70.
7-syn s-P h en yl-7-a n ti-[2′-m et h oxy-5′-(a cet yloxy)-1′(Z)-
p en ten yl]-2-oxa -cis-bicyclo[3.2.0]h ep ta n -6-on e (33). Re-
fluxing 0.2 g (0.73 mmol) of 8e in 2 mL of dry benzene for 2 h
in the presence of 160 mg (3 equiv) of 4,5-dihydrofuran for 2
h followed by removal of the solvent left a brown residue.
Purification by chromatography (eluent 1:6 EtOAc:petroleum
2-P h en yl-3-tr a n s-(4′′-p h en yl-2′′-tr ia zolyl)-4-cis-a zid o-4-
(3′-h yd r oxyp r op yl)cyclobu ta n on e Hem ik eta l (19a ). Re-
crystallization from EtOAc-hexane gave 70 mg of white
crystals: mp 142 °C; 1H NMR δ 7.90 (s, 1H), 7.80 (m, 2H),
7.38 (m, 8H), 5.48 (d, J ) 10 Hz, 1H), 4.78 (d, J ) 10 Hz, 1H),
4.05 (dt, J ) 12, 6 Hz, 1H), 3.91 (dt, J ) 12, 7 Hz, 1H), 3.02
(OH), 2.04 (dt, J ) 14, 9 Hz, 1H), 1.71 (m, 1H), 1.62 (dt, J )
14, 3 Hz, 2H); 13C NMR δ 148.4 (s), 133.6 (s), 131.7 (d), 129.9
(s), 128.9, 128.7, 128.2, 127.60, 126.0, 96.8 (s), 66.2 (s), 63.7
(d), 62.1 (t), 48.9 (d), 23.9 (t), 19.2 (t); IR (neat) 3351, 2110
cm-1; MS CI m/e 389 (MH+), 361 (MH+ - N2), 346 (MH+
-
HN3), 146 (phenyltriazole). Anal. Calcd for C21H20O2N6: C,
64.93; H, 5.19; N, 21.64. Found: C, 64.6; H, 5.15; N, 21.16.
X-ray diffraction crystal data:10 C21H20O2N6 transparent, pris-
matic, 0.4 × 6.3 × 0.3 mm, triclinic, P1 (NO, 2), a ) 11.300(2)
Å, b ) 14.750(2) Å, c ) 5.605(1) Å, e`, a ) 91.19(2)°, b ) 99.25-
(2)°, c ) 81.54(2)°, from 25 reflections, T - 90 K, V ) 914.5(3)
A3, Z ) 2 Fw ) 388.428, Dc ) 1.41 g/mL, Eˆ ) 0.892 cm-1
.
4-Azid o-4-(3′-h yd r oxyp r op yl)-2-p h en yl-3-(4′′-p h en yl-2′′-
tr ia zolyl)cyclobu ta n on e Hem ik eta l (19b). Recrystallized
from EtOAc-hexane: mp 155 °C; 1H NMR δ 7.95 (s, 1H), 7.80
(m, 2H), 7.35 (m, 8H), 5.36 (d, J ) 10 Hz, 1H), 4.81 (d, J ) 10
Hz, 1H), 3.77 (m, 2H), 3.40 (OH), 2.45 (m, 2H), 2.2-1.9 (m,
2H); 13C NMR δ 148.7 (s), 134.0 (s), 131.8, (d), 130.1 (s), 128.8,
128.3, 128.0, 127.4, 94.9 (s), 69.4 (s), 61.1 (t), 59.8 (d), 54.4
(d), 25.3 (t), 22.1 (t); IR (neat) 2100 cm-1; MS CI m/e 361 (MH+
- N2), 146 (phenyltriazole).
4-Azid o-4-(3′-h yd r oxyp r op yl)-2-p h en yl-3-(4′′-p h en yl-1′′-
tr ia zolyl)cyclobu ta n on e Hem ik eta l (19c). Recrystallized
from EtOAc-hexane: mp 152 °C; 1H NMR (acetone-d6), δ 8.62
(s, 1H), 7.92 (m, 10H), 5.49 (d, J ) 11 Hz, 1H), 4.63 (d, J ) 11
Hz, 1H), 3.82 (td, J ) 11, 1.5 Hz, 1H), 3.72 (dm, J ) 11 Hz,
1H), 2.22 (m, 2H), 1.92 (m, 2H); 13C NMR δ 147.4 (s), 135.0
(s), 129.2 129.0, 128.5, 128.3, 127.6, 1259, 121.1 (d), 96.6 (s),
68.6 (s), 61.0 (t), 56.0 (d), 55.3 (d), 25.1 (t), 22.7 (t); IR (neat)
2100 cm-1; MS CI m/e 361 (MH+ - N2), 146 (phenytriazole).
Rea ction of 8a w ith Na N3. 4-Meth oxy-2-p h en yl-3-(4′-
p h en yl-2′-tr ia zolyl)-4-(3′-h yd r oxyp r op yl)cyclobu ta n on e
Hem ik eta l (27). Treatment of 50 mg (0.13 mmol) of 8a with
28 mg (2 equiv) of NaN3 and 0.1 g of LiClO4 in acetone for 3 h
afforded after workup a mixture of products. Chromatography
with 1:4 EtOAc:hexane afforded 15 mg of the major product
27 in 30% yield: mp 139-140 °C; 1H NMR δ 7.89 (s, 1H), 7.79
(m, 2H), 7.35 (m, 8H), 5.27 (d, J ) 10 Hz, 1H), 4.70 (d, J ) 10
Hz, 1H), 4.02 (s, OH), 3.95 (m, 2H), 3.60 (s, 3H), 2.0-1.6 (m,
4H); 13C NMR δ 148.0 (s), 134.1 (s), 131.3 (d), 128.9, 128.7,
128.4, 127.92, 127.1, 125.9, 94.7 (s), 79.7 (s), 65.9 (d), 60.9 (t),
52.0 (q), 48.3 (d), 19.1 (t), 18.5 (t); IR 3344, 1597, 1463; MS CI
m/e 378 (MH+), 346 (MH+ - MeOH), 146 (phenyltriazole).
Rea ction of 9b w ith Na N3. 2-(P h en ylth io)-5-p en ta n o-
lid e (25b). Treatment of 0.1 g (0.32 mmol) of 9b with 65 mg
(3 equiv) of NaN3 and 0.1 g of LiClO4 in acetone for 3 h afforded
a mixture of two products: phenyltriazole (24) identical to
authentic 24 prepared according to ref 18 (mp 141 °C (lit.18
143-145 °C)) and lactone 25b in a 1:1 ratio. Chromatography
of the mixture (eluent EtOAc:hexane 1:6) gave 30 mg of 25b
in 45% yield (oil): 1H NMR δ 7.45 (m, 2H), 7.34 (m, 3H), 4.40
(m, 2H), 3.92 (t, J ) 7 Hz, 1H), 2.4-1.8 (m, 4H); 13C NMR δ
169.5 (s), 133.4, 132.8 (s), 129.2, 127.6, 68.9 (t), 46.7 (d), 26.7
(t), 21.2 (t); IR 1730 cm-1; MS CI m/e 209 (MH+), 236 (MC2H5+),
181(MH+ - CO).
1
ether) afforded 143 mg of 33 as an oil in 65% yield: H NMR
(benzene-d6) δ 7.50 (m 2H), 7.20 (m, 3H), 4.52 (s, 1H), 4.47
(dd, J ) 5.5, 0.5 Hz, 1H), 3.86 (dt, J ) 11, 6.5 Hz, 1H), 3.78
(dt, J ) 11, 7 Hz, 1H), 3.62 (ddd, J ) 9, 5.5, 12 Hz, 1H), 3.50
(ddd, J ) 9, 8, 2.5 Hz, 1H), 3.38 (td, J ) 9.5, 6 Hz, 1H), 3.15
(s, 3H), 2.33 (m, 2H), 1.91 (ddm, J ) 12.5, 6 Hz, 1H), 1.66 (s,
3H), 1.60 (m, 1H), 1.40 (m, 2H); 13C NMR δ 209.0 (s), 170.0
(s), 163.2 (s), 139.8 (s), 128.4, 127.8, 126.9, 98.8 (d), 83.2 (d),
71.5 (s), 69.7 (t), 62.2 (d), 54.3 (q), 28.7 (t), 28.6(t), 26.1 (t),
20.5 (q); MS CI m/e 345 (MH+), 313 (M - MeOH), 285 (M -
AcOH); HRMS calcd for C20H24O5 344.1628, found 344.1537.
8-tr a n s-P h en yl-8-[2′-m eth oxy-5′-(a cetyloxy)-1′(E)-p en -
ten yl]-cis-bicyclo[4.2.0]oct-2-en -7-on e (34). Refluxing 0.2
g (0.73 mmol) of 8e in 10 mL of dry benzene, in the presence
of 175 mg (3 equiv) of 1,3-cyclohexadiene overnight, gave after
removal of the solvent a brown residue. Purification by
chromatography, eluent EtOAc:hexane 1:6, afforded 143 mg
of 34 as an oil in 55% yield: 1H NMR δ 7.30 (m, 5H), 5.72
(dddd, J ) 10.5, 5.5, 2.5, 1 Hz, 1H), 5.21 (dm, J ) 10.5 Hz,
1H), 4.95 (s, 1H), 3.93 (m, 1H), 3.76, 3.69 (dt, J ) 11, 6.5 Hz,
2H), 3.59 (s, 3H), 2.96 (ddt, J ) 9.5, 4, 2 Hz, 1H), 2.12* (m,
1H), 2.02 (m, 1H), 1.96 (s, 3H), 1.95 (m, 1H), 2.01 (m, 2H),
1.54 (m, 1H), 1.51, 1.28 (ddq, J ) 13.5, 9, 7 Hz, 2H); 13C NMR
δ 208.5 (s), 170.9 (s), 162.6 (s), 140.5 (s), 129.5 (d), 127.7, 127.5,
126.6 (d), 126.3, 102.5 (d), 69.7 (s), 64.1 (t), 54.6 (q), 53.8 (d),
40.4 (d), 25.3 (t), 21.3 (t), 20.8 (q), 18.6(t); IR (neat) 2930, 1763,
1736, 1641, 1239 cm-1; MS CI m/e 355 (MH+), 323 (MH+
-
MeOH). Anal. Calcd for C22H26O4: C, 74.54; H, 7.39.
Found: C, 74.23; H, 7.30. *The chemical shift was obtained
from a hetero COSY NMR experiment.
11-Acetoxy-1,8-dim eth oxy-6-ph en yl-5-(tr im eth ylsiloxy)-
1,5,7(E,Z,Z)-u n d ectr ien -3-on e (36). Ketone 36 was obtained
from 8e (0.22 g, 0.8 mmol) and 1.25 equiv of 35 by refluxing
in 1 mL of dry benzene for 4 h (46%) and chromatography
(eluent 1:4 to 1:2 EtOAc:hexane): 1H NMR (acetone-d6) δ 7.67
(d, J ) 12.5 Hz, 1H), 7.40 (m, 2H), 7.27 (m, 3H), 5.76 (d, J )
12.5 Hz, 1H), 5.23 (s, 1H), 3.87 (t, J ) 7.5 Hz, 2H), 3.46 (s,
2H), 3.75 (s, 3H), 3.60 (s, 3H), 2.09 (m, 2H), 1.93 (s, 3H), 1.67
(dt, J ) 7.5,6.5 Hz, 2H); 13C NMR δ 195.1 (s), 170.8 (s),163.5
(d), 160.2 (s), 145.1 (s), 130.7, 128.4, 126.7, 119.7 (s), 98.4 (d),
64.5 (t), 58.0(q), 54.9 (q), 48.5 (t), 28.5 (t), 26.6 (t), 20.7 (q), 0.7
(q).
6-Met h oxy-2′-[6′-a cet oxy-3′(Z)-m et h oxy-1′-p h en yl-2′-
h exen -1′-yl]-5,5-d ih yd r o-4-p yr a n on e (37). Hydrolysis of 36
with 1.2 equiv of CsF in CH2Cl2 followed by chromatography
(eluent 1:3 EtOAc:hexane) afforded dihydropyranone 37 in 45%
yield. The product is a mixture of diastereomers (two chiral
centers): 1H NMR δ 7.42 (m, 2H), 7.34 (m, 2H), 7.26 (m, 1H),
5.57, 5.48 (each d, J ) 0.5 Hz, 1H), 5.46, 5.48 (dd, J ) 3, 2 Hz,
Th er m olysis of Cyclobu ten on e 9b. A solution of 0.2 g
(0.6 mmol) of 9b in 5 mL of dry MeOH was refluxed for 4 h.
Removal of the solvent left an oil. Chromatography of the
residue (eluent 1:4 to 1:2 EtOAc:hexane) afforded 70 mg of
lactone 31 (35%) and 120 mg of a mixture of Z/E hydroxy esters
29, 30 (55%).