Natural Products
hexane/EtOAc/NEt
FULL PAPER
3
200:20:6, #17–27 cyclohexane/EtOAc/NEt
200:40:6). Fractions #21–27 contained
2 (42.0 mg, 37%) and fractions #36–45 contained 16 (41.3 mg, 36%) as
3
200:30:6,
ing bath was removed and the solution stirred for another 15 min. The
solvent was evaporated in vacuo and the residue purified by flash chro-
matography (2 cm, cyclohexane, #5–18 cyclohexane/EtOAc 10:1, product
in #10–18) to afford the title compound (416 mg, 87%) as a brown solid.
#
28–45 cyclohexane/EtOAc/NEt
3
2
1
yellow oils, which rapidly turned brown. Analytic data for 16: H NMR
500 MHz, CDCl ): d=0.80–0.95 (m, 3ꢄSnCH CH CH CH ), superim-
poses 0.88 (t, Jvic =7.4, 3ꢄSnCH CH CH CH ), 1.30 (tq, both Jvic =7.4,
ꢄSnCH CH CH CH ), 1.40–1.57 (m, 3ꢄSnCH CH CH CH ), 1.83 (d,
OH,4’ =3.7, OH), AB signal, which is not completely resolved in the A
1
(
3
2
2
2
3
M.p. 368C; H NMR (300 MHz, CDCl ): d=0.06 [s, Si(CH ) ], 0.91 [s,
3
3 2
4
4
2
2
2
3
3 3 1,2 2 3,2
C(CH ) ], 4.26 (dd, J =3.9, J1,3 =2.3, 1-H ), 5.84 (dt, J =15.7, J3,1 =
3
2
2
2
3
2
2
2
3
3
2.3, 3-H), 6.40 (dt, J2,3 =15.7, J2,1 =3.9, 2-H); IR (CDCl ): n˜ =2955, 2930,
ꢁ
1
J
2055, 1730, 1255, 1135, 1065, 1010, 835 cm ; elemental analysis calcd
(%) for C H IOSi (346.0): C 45.09, H 5.53; found: C 45.47, H 5.71.
part (d
A
=2.39, d
B
=2.50, JAB =13.9, in addition split by JA,4’ =JA,6’ =7.1,
1
3
19
4
4
JA,7’ =1.0, JB,6’ =6.2, JB,4’ =5.0,
J
B,7’ =1.3, 5’-H
2
), 4.34 (m, 4’-H), 5.81 (d,
Z-5-[all-trans-14-(tert-Butyldimethylsiloxy)-4-hydroxy-2,6,12-tetradeca-
triene-8,10-diynylidene]-2(5H)-furanone (28) as a 50:50 mixture with the
J
1’,2’ =11.2, 1’-H), 5.93 (ddd, J6’,7’ =18.8, J6’,5’-H(A) =6.9, J6’,5’-H(B) =6.2, 6’-H),
4
6
.06 (ddd, J3’,2’ =15.4, J3’,4’ =5.8,
J
3’,1’ =0.7, 3’-H), one peak superimposed
5
0
-hydroxy isomer (iso-28): A mixture of [Pd(dba)
2
] (3.3 mg, 5.8 mmol,
4
4
by 6.11 (dt, J7’,6’ =18.9, J7’,5’-H(A) = J7’,5’-H(B) =1.2, 7’-H), 6.18 (d, J3,4 =5.4, 3-
H)*, 6.79 (ddd, J2’,3’ =15.5, J2’,1’ =11.3, Jallyl =1.4, 2’-H), 7.37 (d, J4,3 =5.2, 4-
H); elemental analysis calcd (%) for C23
.05 equiv) and AsPh (7.0 mg, 23 mmol, 0.2 equiv) was added to a so-
lution of diyne 27 (60 mg, 0.17 mmol, 1.5 equiv) and a 53:47 mixture of
the stannanes 16 and iso-16 (54.0 mg, 0.115 mmol) in THF (3 mL). After
3
38 3
H O Sn (480.2): C 57.40, H
7
.96; found: C 57.44, H 8.12.
2
4 h the solvent was evaporated in vacuo and the residue purified by
1
Analytic data for 22: H NMR (500 MHz, CDCl
3
; peak of contaminant at
CH ), superimposes 0.90 (t,
), 1.32 (tq, both vic =7.3, 3ꢄ
), 1.44–1.56 (m, 3ꢄSnCH CH CH CH ), 1.89 (d,
OH,4’ =2.8, OH), AB signal (d =2.41, d =2.59, JAB =13.7, in addition
split by JA,4’ =9.2, flanked by Sn isotope satellites as 1 incompletely re-
flash chromatography (2 cm, cyclohexane/EtOAc 3:1, #11–18 cyclohex-
ane/EtOAc 1:1, product in #16–18) to afford the title compounds as an
d=5.80): d=0.87–1.01 (m, 3ꢄSnCH
vic =7.3, 3ꢄSnCH CH CH CH
SnCH CH CH CH
2
CH
2
CH
2
3
1
J
2
2
2
3
J
inseparable 50:50 mixture (24.0 mg, 51%) as yellow oils; H NMR
2
2
2
3
2
2
2
3
(300 MHz, CDCl ): d=0.07 [s, Si(CH ) ], 0.91 (s, C(CH ) ], 2.42–2.57 [m,
3
3
2
3 3
J
A
B
5’-H (28), 4’-H2 (iso-28)], 4.25 (incompletely resolved dd, J14’,13’ =3.7,
J14’,12’ =1.8, 14’-H ), 4.31–4.45 [m, 4’-H (28), 5’-H (iso-28)], 5.78–5.90 and
5.96–6.42 (2 m ꢅ 2 H bzw. 5H; 3-H, 1’-H, 3’-H, 6’-H, 7’-H, 12’-H, 13’-H),
6.68 [dd, J2’,3’ =15.5, J2’,1’ =11.3, 2’-H (28)], 6.79 [incompletely resolved
2
4
2
3
3
solved d, JA,119Sn ꢀ JA,117Sn ꢀ60, JB,4’ =4.0, flanked by Sn isotope satellites
3
3
as 1 incompletely resolved dm,
J
B,119Sn ꢀ JB,117Sn ꢀ17, 5’-H
2
), 4.24 (m, 4’-
4
H), 5.36 [d, Jgem =2.6, each peak flanked by Sn isotope satellites as 2 in-
ddt, J2’,3’ ꢀ15.5, J2’,1’ ꢀ11.3, J2’,4’ ꢀ1.1, 2’-H (iso-28)], 7.37 [d, J4,3 =5.2, 4-
3
3
terlocked d,
J
7’-H(Z),119Sn =60.6,
J
7’-H(Z),117Sn =58.1, 7’-H(Z)]*, 5.82 (d, J1’,2’
=
H (28)*], partly superimposed by 7.38 [d, J4,3 =4.7, 4-H (iso-28)*]; *inter-
2
1
J
1.4, 1’-H), low-field peak is exactly on middle peak of 5.81 [ddd, Jgem
=
changeable; IR (CDCl
185, 1135, 1045, 975, 830 cm ; (m/z)=353.12091 ꢃ 5 mDa [M ], con-
firmed by HRMS (EI, 70 eV).
Z-5-[all-trans-14-(tert-Butyldimethylsiloxy)-2,4,6,12-tetradecatetraene-
3
): n˜ =2945, 2860, 1750, 1545, 1415, 1335, 1260,
4
4
7’-H(E),5’-H(A) = J7’-H(E),5’-H(B) =1.7, each peak flanked by Sn isotope satel-
ꢁ1
+
1
3
3
lites as 2 d,
J
7’-H(E),119Sn =132.7,
J
7’-H(E),117Sn =127.4, 1’-H, 7’-H(E)]*, 6.06
4
(
ddd, J3’,2’ =15.5, J3’,4’ =6.0, J3’,1’ =0.7, 3’-H), 6.18 (d, J3,4 =5.00, 3-H), 6.80
(
ddd, J2’,3’ =15.5, J2’,1’ =11.3, Jallyl =1.4, 2’-H), 7.37 (d, J4,3 =5.4, 4-H); *dis-
8
8
,10-diynylidene]-2(5H)-furanone (trans-29): At ꢁ788C Tf
7.8 mmol, 1.5 equiv) was added to a 50:50 mixture of the alcohols 28 and
(29.5 mg, 293 mmol, 5.0 equiv) in
(5 mL). After 25 min the solution was allowed to warm to ꢁ208C
within 2 h. The solution was directly submitted to flash chromatography
2 cm, cyclohexane/EtOAc 3:1). Fractions #4–9 contained 9.0 mg of se-
2
O (24.7 mg,
3
tinguishable by comparison with the
J
Sn,H coupling constants of vinyl-
3
3
[59]
stannans: JH(Z),Sn =50–75 Hz and JH(E),Sn =100–150 Hz; elemental anal-
iso-28 (24.0 mg, 58.5 mmol) and NEt
CH Cl
3
ysis calcd (%) for C23
38 3
H O Sn (480.2): C 57.40, H 7.96; found: C 57.34, H
2
2
8
.13.
[
3]
1
,4-Dichloro-2-butyne (23):
(
[30]
trans-2-Heptene-4,6-diyn-1-ol (25): Li (6.80 g, 1.00 mol, 6.0 equiv) and
a catalytic amount of Fe(NO ·9H O were dissolved in liquid NH
verely contaminated product(s) making a structural assignment impossi-
ble. Fractions #10–15 contained the title compound trans-29 (11.0 mg,
3
)
2
2
3
1
(
4
1000 mL). After stirring at ꢁ458C for 1 h 1,4-dichloro-2-butyne (23;
48%) as a yellow solid. H NMR [500 MHz, CDCl ; contains some con-
3
0.96 g, 333 mmol, 2.0 equiv) was added within 75 min. After 15 min epi-
taminant(s)]: d=0.07 [s, Si(CH ) ], 0.91 (s, C(CH ) ], 4.27 (dd, J
14’,13’
=3.8,
3
2
3
3
4
chlorohydrin (24; 15.42 mg, 0.1667 mol) was added within 40 min at the
same temperature. After 3.5 h NH Cl (18 g) was added and the NH was
allowed to evaporate overnight. H O (400 mL) was added and the aq.
phase extracted with tBuOMe (5ꢄ200 mL). The combined organic
phases were dried with MgSO and the solvent evaporated in vacuo. The
residue was purified by flash chromatography {5 cm, Al B [desacti-
2 7’,6’
J14’,12’ =2.4, 14’-H ), 5.77 (d, J =15.4, 7’-H), 5.89 (d, J1’,2’ =11.8, 1’-H;
completely superimposes and therefore only visible by the integral: J12’,13’
4
3
2
presumably up to 16 Hz, 12’-H), 6.18 (d, J3,4 =5.4, 3-H), 6.39 (dt, J13’,12’
15.7, J13’,14’ =4.0, 13’-H), 6.41–6.55 (m, 3’-H, 4’-H, 5’-H,), 6.78 (dd, J6’,7’
15.2, J6’,5’ =10.1, 6’-H), partly interlocked with 6.83 (dd, J2’,3’ =13.9, J2’,1’
=
=
=
4
2
O
3
11.8, 2’-H), 7.37 (d, J4,3 =5.2, 4-H); the H,H-correlation spectrum con-
vated with 10 vol.% HOAc (1.6m)], cyclohexane, #20–39 cyclohexane/
EtOAc 3:1, #40–49 cyclohexane/EtOAc 1:1, product in #32–49} to afford
the title compound [2.943 g, 17%, contaminated with 1.472 g EtOAc
firms the assignment by the following cross-peaks: 1) 14’-H (d=4.27) ,
2
13’-H (d=6.39) , 12’-H (d=5.89); 2) 7’-H (d=5.77) , 6’-H (d=6.78)
, amongst others 5’-H (d=6.41–6.55, together with 3’-H and 4’-H); 3)
1’-H (d=5.89) , 2’-H (d=6.83) , 3’-H (d=6.41–6.55, together with 4’-
[
30]
(
40 mol%=33 wt%); ref.: 21%] as a brown solid. Further removal of
the solvent led to complete decomposition of the product.
H and 5’-H); 4) 3-H (d=6.18) , 4-H (d=7.37); IR (CDCl ): n˜ =2930,
3
ꢁ1
trans-1-(tert-Butyldimethylsiloxy)-2-heptene-4,6-diyne (26): At 08C tBu-
2875, 1775, 1750, 1530, 1445, 1415, 1330, 1260, 1120, 1065, 1045, 835 cm
(m/z)=392.18077 ꢃ 5 mDa [M ] confirmed by HRMS (EI, 70 eV).
Z-5-(all-trans-14-Hydroxy-2,4,6,12-tetradecatetraene-8,10-diynylidene)-
;
+
Me
solution of heptendiynol 25 (849 mg, 8.09 mmol) and imidazole
1.099 g, 16.17 mmol, 2.0 equiv) in CH Cl (20 mL). After 2 h the solution
O (50 mL) and the aq. phase extracted with CH Cl
2
SiCl (50 wt% in toluene, 1.215 g, 8.10 mmol, 1.0 equiv) was added to
a
(
2
2
2(5H)-furanone (30): At 08C HF/pyridine complex (50 mL, 1.2 mmol,
44.7 equiv) was added to silyl ether trans-29 (10.5 mg, 26.8 mmol) in THF
(5 mL). After 2 h 15 min more HF/pyridine complex (100 mL, 2.4 mmol,
was poured on H
2
2
2
(
2ꢄ20 mL). The solvent was evaporated in vacuo and the residue puri-
fied by flash chromatography (2 cm, cyclohexane/EtOAc 30:1, product in
5–19) to afford the title compound (1.328 g, 75%) as a brown oil.
8
9.6 equiv) was added. Silica gel (ca. 200 mg) was added after 2 h 45 min
#
and the mixture stirred at 08C for 15 min. After filtration through a pad
of Celite, the solvent was evaporated in vacuo and the residue purified
by flash chromatography (2 cm, cyclohexane/EtOAc 3:1, #10–21 cyclo-
hexane/EtOAc 1:3, product in #16–21) affording an orange solid
1
H NMR (300 MHz, CDCl
3
): d=0.07 [s, Si(CH
s, 7-H), 4.25 (dd, J1,2 =3.8, J1,3 =2.3, 1-H
2
3
)
2
], 0.91 [s, C(CH
), 5.80 (dm, J3,2 ꢀ15.7, 3-H),
.43 (dt, J2,3 =15.8, J2,1 =3.9, 6-H); IR (CDCl ): n˜ =3305, 2955, 2930, 2885,
860, 2205, 1255, 1195, 1135, 1065, 1010, 835 cm ; elemental analysis
20OSi (221.1): C 70.85, H 9.15; found: C 70.62, H 8.89.
trans-1-(tert-Butyldimethylsiloxy)-7-iodo-2-heptene-4,6-diyne (27): At
788C BuLi (1.4m in hexane, 1.2 mL, 1.7 mmol, 1.2 equiv) was added to
a solution of enediyne 26 (300 mg, 1.37 mmol) in THF (10 mL). After
min I (423 mg, 1.64 mmol, 1.2 equiv) was added. After 25 min the cool-
3 3
) ], 2.40
4
(
6
2
3
ꢁ
1
(
5.0 mg). It contained aliphatic impurities, therefore the yield of the title
calcd (%) for C13
H
1
compound is < 67%; H NMR (300 MHz, CDCl
terial): d=4.27 (dd, J14’,13’ =4.6, J14’,12’ =1.8, 14’-H
3
; contains insoluble ma-
4
2
), 5.77 (d, J7’,6’ =15.1, 7’-
ꢁ
H), 5.90 (d, J1’,2’ =11.8, 1’-H; completely superimposes and therefore only
visible by the integral: J12’,13’ presumably up to 16 Hz, 12’-H), 6.19 (d,
J3,4 =5.2, 3-H), 6.37–6.58 (m, 3’-H, 4’-H, 5’-H, 13’-H), 6.73–6.90 (m, 2’-H,
5
2
Chem. Eur. J. 2005, 11, 1610 – 1624
ꢂ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1619