Notes
As expected, the reaction of 4 with 9 run after five
freeze-thaw cycles under otherwise the same conditions
as mentioned earlier indeed produced freelingyne (1) in
J . Org. Chem., Vol. 62, No. 24, 1997 8593
of p-TsOH (30 mg, 0.16 mmol) was stirred at 23 °C for 1 h. The
mixture was diluted with ether, washed with aqueous NaHCO
and NaCl, dried over MgSO , filtered, and concentrated. Flash
3
4
chromatography (75:25 pentane-ether) afforded 1.95 g (97%)
6
1% NMR yield along with the alkyne dimer 10 formed
1
of the title compound: H NMR δ 1.91 (s, 3 H), 2.7-3.0 (m, 1
in 20% yield based on 9. The stereoisomeric purity of 1
was >98%. Further improvement of the Pd-catalyzed
cross-coupling-lactonization tandem process and its ap-
plication to the synthesis of other γ-alkylidenebutenolides
are under investigation.
H), 4.10 (s, 2 H), 5.72 (s, 1 H), 6.4-6.5 (m, 1 H), 7.3-7.4 (m, 1
H), 7.59 (s, 1 H); 13C NMR δ 16.40, 66.45, 84.02, 88.24, 104.32,
107.79, 112.35, 142.69, 144.91, 149.76; IR (neat) 3356, 3150,
-
1
2
(
(
912, 2198, 1506, 1442, 1350, 1162 cm ; MS (EI, 70 eV) m/z
+
relative intensity) 162 (M , 58), 147 (38), 105 (80), 91 (100), 77
75).
(
E)-5-(3-F u r a n yl)-2-m eth yl-2-p en ten -4-yn a l (7). To a so-
lution of (E)-5-(3-furanyl)-2-methyl-2-penten-4-yn-1-ol (630 mg,
.9 mmol) in CH Cl
Exp er im en ta l Section
3
2
2
(25 mL) at 0 °C was added Dess-Martin
11
Gen er a l P r oced u r es. All reactions involving organometallic
periodinane (5.1 g, 12 mmol). After 1 h at 23 °C, silica gel (5
g) was added, and the solvent was removed in vacuo. Flash
chromatography (CH
1
13
reagents were conducted under dry Ar atmosphere. H and
NMR spectra were recorded in CDCl on a 300 MHz spectrom-
eter. NMR yields were determined using CH Br as an internal
C
3
1
2
Cl
2
) afforded 621 mg (100%) of 7: H NMR
2
2
δ 1.95 (s, 3 H), 6.45-6.5 (m, 1 H), 6.49 (s, 1 H), 7.40 (s, 1 H),
standard. GLC analysis was performed with a column packed
with SE-30 Chromosorb W using a TC detector. Unless other-
wise mentioned, commercially available reagents were used as
received. THF was distilled from sodium benzophenone ketyl.
13
7
1
2
.69 (s, 1 H), 9.45 (s, 1 H); C NMR δ 11.57, 87.36, 98.07, 106.99,
12.09, 128.56, 143.27, 146.36, 147.16, 193.63; IR (neat) 3150,
-1
818, 2716, 2206, 1686, 1380, 1200 cm ; MS (EI, 70 eV) m/z
relative intensity) 160 (M , 75), 131 (77), 103 (70), 92 (100), 77
72).
+
(
(
E)-3-Iod o-2-m et h yl-1-[(t et r a h yd r op yr a n yl)oxy]-2-p r o-
(
5
b
p en e. To a mixture of (E)-3-iodo-2-methyl-2-propen-1-ol (1.98
g, 10 mmol) and 3,4-dihydro-2H-pyran (1.9 mL, 20 mmol) in CH
Cl (20 mL) at 0 °C was added p-TsOH (190 mg, 1 mmol). The
resulting mixture was stirred for 1 h at 23 °C, diluted with ether,
washed with aqueous NaHCO and NaCl, dried over MgSO
filtered, and concentrated. Flash chromatography (95:5 pen-
(
3E)-1,1-Dibr om o-6-(3-fu r a n yl)-3-m eth yl-1,3-h exa d ien -5-
yn e (8). A mixture of Ph P (6.14 g, 23.4 mmol), CBr (3.88 g,
1.7 mmol), and K CO (540 mg, 3.9 mmol) in CH Cl was stirred
at 23 °C for 30 min. To this was added 7 (621 mg, 3.9 mmol)
in CH Cl (8 mL). After 20 min, silica gel (1 g) was added, and
the solvent was removed in vacuo. Flash chromatography
2
-
3
4
2
1
2
3
2
2
12
3
4
,
2
2
1
tane-ether) afforded 2.36 g (84%) of the title compound:
NMR δ 1.4-2.0 (m, 6 H), 1.85 (s, 3 H), 3.4-3.6 (m, 1 H), 3.75-
H
1
(
pentane) afforded 1.17 g (95%) of 8: H NMR δ 2.24 (s, 3 H),
5
.88 (s, 1 H), 6,47 (d, J ) 0.8 Hz, 1 H), 7.06 (s, 1 H), 7.39 (s, 1
3
2
6
1
.9 (m, 1 H), 3.9-4.05 (m, 1 H), 4.1-4.25 (m, 1 H), 4.60 (d, J )
.6 Hz, 1 H), 6.25 (s, 1 H); 13C NMR δ 19.15, 21.63, 25.31, 30.36,
1.98, 70.47, 78.14, 97.44, 144.49; IR (neat) 3058, 2942, 1622,
13
H), 7.65 (s, 1 H); C NMR δ 18.25, 88.65, 88.88, 89.63, 107.72,
1
2
3
12.26, 113.91, 138.64, 142.94, 143.80, 145.31; IR (neat) 3150,
-1
200, 1772, 1094 cm ; MS (EI, 70 eV) m/z (relative intensity)
16 (M , 7), 234 (9), 128 (91), 51 (100); HRMS (EI) calcd for
440, 1282, 1022 cm-1
.
+
(
E )-2-Me t h yl-1-[(t e t r a h yd r op yr a n yl)oxy]-2-p e n t e n -4-
yn e (5). To a solution of (E)-3-iodo-2-methyl-1-[(tetrahydropy-
ranyl)oxy]-2-propene (5.31 g, 18.8 mmol) in THF (20 mL) at 23
C was added ethynylmagnesium chloride (0.5 M in THF, 56.5
+
C
11
H
8
Br
2
O (M ) 314.9020, found 314.9008.
(
E)-6-(3-F u r a n yl)-3-m eth yl-3-h exen e-1,5-d iyn e (9). To a
solution of 8 (1.58 g, 5.0 mmol) in THF (20 mL) was added NaN-
SiMe (1.0 M in THF, 11.0 mL, 11.0 mmol, -100 °C, 10 min)
followed by n-BuLi (2.5 M in hexanes, 8.8 mL, 22.0 mmol, -100
°
(
3 2
)
9
mL, 28.2 mmol) followed by Pd(PPh
stirring for 1 h, the mixture was diluted with ether, washed with
aqueous NH Cl and NaCl, dried over MgSO , filtered, and
3 4
) (1.09 g, 0.94 mmol). After
19
°
C, 10 min). The reaction mixture was quenched at -100 °C
with MeOH, warmed to 23 °C, diluted with ether, washed with
aqueous NH Cl and NaCl, dried over MgSO , filtered, and
concentrated. Flash chromatography (pentane) afforded 713 mg
91%) of 9: 1H NMR δ 2.08 (s, 3 H), 3.17 (s, 1 H), 6.05 (s, 1 H),
.45 (d, J ) 1.8 Hz, 1 H), 7.39 (t, J ) 1.6 Hz, 1 H), 7.64 (s, 1 H)
4
4
concentrated. Flash chromatography (95:5 pentane-ether) af-
4
4
1
forded 3.18 g (94%) of 5: H NMR δ 1.4-2.0 (m, 6 H), 1.87 (s, 3
H), 3.04 (d, J ) 1.1 Hz, 1 H), 3.4-3.55 (m, 1 H), 3.75-3.85 (m,
(
1
(
3
2
(
H), 3.89 (d, J ) 14.2 Hz, 1 H), 4.14 (d, J ) 14.2 Hz, 1 H), 4.57
6
13
t, J ) 3.2 Hz, 1 H), 5.53 (s, 1 H); C NMR δ 16.63, 19.06, 25.26,
13
ppm; C NMR δ 20.14, 80.29, 85.19, 87.77, 90.00, 107.55, 112.26,
0.30, 61.81, 69.88, 80.82, 97.57, 104.32, 149.45; IR (neat) 3292,
1
17.00, 129.37, 142.94, 145.38 ppm; IR (neat) 3314, 2178, 1164
-
1
944, 2102, 1638, 1442, 1202, 1036 cm ; MS (CI, 70 eV) m/z
-1
+
cm ; MS (EI, 70 eV) m/z (relative intensity) 156 (M , 100), 139
+
relative intensity) 181 (M + 1, 28), 85 (100); HRMS (CI) calcd
+
(
5), 127 (49), 102 (25); HRMS (EI) calcd for C11
56.0575, found 156.0577.
(
(490 mg, 2.47 mmol) in CH Cl (20 mL) at 0 °C were added
2 2
Celite (1.1 g) and PCC (1.07 g, 4.8 mmol). The resulting mixture
was stirred at 0 °C for 4 h, filtered, washed with aqueous
3 4
NaHCO and NaCl, dried over MgSO , filtered, and concentrated
to afford crude (Z)-3-iodo-2-methylpropenal. This compound was
H
8
O (M )
+
for C11
E)-5-(3-F u r a n yl)-2-m eth yl-1-[(tetr a h yd r op yr a n yl)oxy]-
-p en ten -4-yn e (6). To a solution of 5 (3.288 g, 18.3 mmol) in
THF were added sequentially n-BuLi (2.5 M in hexane, 7.6 mL,
(4.28 g, 19
16 2
H O (M + 1) 181.1229, found 181.1223.
1
(
Z)-3-Iod o-2-m eth ylp r op en oic Acid (4).20 To a solution of
2
36
1
9 mmol, -78 °C, 20 min), a solution of dry ZnBr
2
mmol) in THF (10 mL) (-78 to 23 °C), 3-iodofuran (1.7 M in
THF, prepared by treatment of 3-bromofuran with 1.1 equiv of
n-BuLi in THF followed by iodinolysis with I
3.8 mmol), and Pd(PPh (1.06 g, 0.92 mmol). The resulting
mixture was stirred for 1 h at 23 °C, quenched with aqueous
NH Cl, diluted with ether, washed with aqueous NaCl, dried
over MgSO , filtered, and concentrated. NMR examination
indicated the formation of 6 in 82% yield along with unreacted
(16%). Chromatographic purification (95:5 pentane-ether)
2
in THF, 14.0 mL,
not characterized due to its rapid decomposition. To a mixture
1
8
2
3 4
)
of crude (Z)-3-iodo-2-methylpropenal in CH
PO ‚H O (104 mg, 0.75 mmol) in H O (2 mL), and H
.5 mL, 30 mmol) at 0 °C was added dropwise a solution of
NaClO (80%, 390 mg, 3.5 mmol) in H O (4 mL). The reaction
3
CN (3 mL), NaH
2
-
4
2
2
2 2
O
(30%,
4
3
4
2
2
mixture was extracted with ether. The aqueous layer was
acidified with 3 M HCl and extracted with ether. The combined
organic layers were dried over MgSO , filtered, and concentrated.
4
5
1
afforded its pure sample: H NMR δ 1.4-2.0 (m, 6 H), 1.92 (s,
3
1
(
H), 3.4-3.55 (m, 1 H), 3.75-3.9 (m, 1 H), 3.96 (d, J ) 14.0 Hz,
H), 4.20 (d, J ) 14.0 Hz, 1 H), 4.62 (t, J ) 3.2 Hz, 1 H), 5.74
The residue was chromatographed (50:50 pentane-ether) to
afford 298 mg (57%, two steps) of 4: 1H NMR δ 2.03 (d, J ) 1.1
s, 1 H) 6.42 (d, J ) 0.7 Hz, 1 H), 7.35 (s, 1 H), 7.58 (s, 1 H); 13
C
13
Hz, 3 H), 8.01 (d, J ) 1.1 Hz, 1 H), 11.63 (br s, 1 H); C NMR
NMR δ 16.84, 19.16, 25.33, 30.40, 61.91, 70.16, 83.89, 97.57,
δ 22.21, 86.08, 137.52, 171.11.
(
1
2
05.53, 107.90, 112.39, 142.66, 144.87, 147.26; IR (neat) 3146,
21
Z)-5-Ben zyliden e-3-m eth yl-5H-fu r an -2-on e (11). A mix-
-
1
942, 1442, 1350, 1202, 1022 cm ; MS (EI, 70 eV) m/z (relative
ture of PhCtCH (23 mg, 0.22 mmol), 4 (42 mg, 0.2 mmol), Pd-
PPh
0.11 mL, 0.8 mmol) in CH
+
intensity) 246 (M , 2), 162 (6), 145 (16), 85 (100); HRMS (EI)
(
3
)
4
(12 mg, 0.01 mmol), CuI (2 mg, 0.01 mmol), and Et
3
N
+
calcd for C15
E)-5-(3-F u r a n yl)-2-m eth yl-2-p en ten -4-yn -1-ol. A solu-
tion of 6 (3.05 g, 12.4 mmol) in MeOH (40 mL) in the presence
18 3
H O (M ) 246.1256, found 246.1257.
(
3
CN (5 mL) was degassed via five
3
a
(
(
19) Grandjean, D.; Pale, P.; Chuche, J . Tetrahedron Lett. 1994, 35,
529.
(20) Larock, R. C.; Zenner, J . M. J . Org. Chem. 1995, 60, 482.
(21) Scheeren, J . W.; Lange, J . Tetrahedron Lett. 1984, 25, 1609.
3
(
18) Negishi, E. In Aspects of Mechanism and Organometallic
Chemistry; Brewster, J . H., Ed.; Plenum Press: New York, 1978; p 285.