Pd-Catalyzed Cycloisomerization of (Z)-2-En-4-yn-1-ols
J . Org. Chem., Vol. 64, No. 21, 1999 7691
AcOEt, 74%): IR (neat) 3341, 2211, 1023 cm-1 1H NMR δ
(m, 1 H), 4.29 (dq, J ) 6.9, 1.1, 2 H), 2.35 (t, J ) 6.9, 2 H),
1.87-1.85 (m, 3 H), 1.59-1.36 (m, 4 H), 0.93 (t, J ) 7.3, 3 H);
MS m/e 152 (1, M+), 109 (100), 95 (44), 81 (65); 1h (pale yellow
oil, hexane/AcOEt from 98:2 to 80:20, 58%).
;
5.40-5.38 (m, 1 H), 4.35 (s, 2H), 2.34 (td, J ) 6.8, 2.0, 2 H),
2.26-2.16 (m, 2 H), 1.59-1.35 (m, 4 H), 1.06 (t, J ) 7.3), 0.92
(t, J ) 7.1, 3 H); MS m/e 166 (7, M+), 137 (18), 123 (92), 81
(100). 1m (pale yellow oil, 6:4 hexane/Et2O, 86%): IR (neat)
(Z)-3-P h en ylp en t-2-en -4-yn -1-ol 1e. The method of Mar-
shall27 and Magriotis28 applied to 3-phenylprop-2-yn-1-ol29 was
employed to prepare (Z)-3-iodo-3-phenylprop-2-en-1-ol. Cou -
p lin g P r oced u r e. To a stirred solution of the vinyl iodide (3.7
g, 14.2 mmol) in Et2NH (42 mL) were added Pd(PPh3)2Cl2 (0.20
g, 0.29 mmol) and CuI (0.29 g, 1.5 mmol). A solution of Me3-
SiCtCH (2.1 g, 21.5 mmol) in Et2NH (5.5 mL) was added
dropwise, and the resulting mixture was stirred at room
temperature for 4 h. After cooling to 0 °C, the mixture was
diluted with Et2O (50 mL) and quenched with 10% HCl. The
aqueous layer was extracted with Et2O, and the combined
organic layers were washed with brine and dried over Na2-
SO4. The solvent was removed under reduced pressure, and a
solution of KF (1.2 g, 20.7 mmol) in MeOH (25 mL) was added
to the residue. The reaction mixture was allowed to stir at
room temperature for 3 h, and then it was diluted with Et2O
(20 mL) and quenched with water (60 mL). The aqueous layer
was extracted with Et2O, and the combined organic layers were
washed with brine (3 × 10 mL), dried (Na2SO4), and evapo-
rated. Column chromatography (hexane/AcOEt from 9:1 to 8:2)
afforded pure 1e as a pale yellow oil (1.2 g, 53%): IR (neat)
1
3377, 2207, 1026 cm-1; H NMR δ 7.49-7.41 (m, 2 H), 7.37-
7.22 (m, 3 H), 5.91 (t, J ) 2.1, 1 H), 4.75 (s, 2H), 2.38 (td, J )
7.0, 2.1, 2 H), 1.60-1.35 (m, 4 H), 0.91 (t, J ) 7.3, 3 H); MS
m/e 214 (74, M+), 171 (96), 157 (70), 141 (72), 128 (100). 1o
(pale yellow oil, hexane/AcOEt from 9:1 to 7:3, 79% based on
3-phenylprop-2-yn-1-ol): IR (neat) 3359, 1489, 1027 cm-1; 1H
NMR δ 7.43-7.27 (m, 10 H), 4.65 (s, 2 H), 2.31 (q, J ) 7.3, 2
H), 1.07 (t, J ) 7.3, 3 H); MS m/e 262 (34, M+), 233 (100), 215
(51), 205 (70). 1p ′ (colorless liquid, bp ) 51-52 °C/1 × 10-2
mmHg, 88%): IR (neat) 3333, 2133, 1249, 843 cm-1; 1H NMR
δ 5.42 (t, J ) 1.9, 1 H), 4.38 (s, 2 H), 2.24 (qd, J ) 7.5, 1.9, 2
H), 1.06 (t, J ) 7.5), 0.19 (s, 9 H); MS m/e 182 (2, M+), 167
(68), 75 (100), 73 (75). 1q ′ (pale yellow oil, 95:5 hexane/
AcOEt, 87%): IR (neat) 3380, 2132, 1020, 845 cm-1; 1H NMR
δ 7.51-7.45 (m, 2 H), 7.41-7.29 (m, 3 H), 5.95 (s, 1 H), 4.82
(s, 2 H), 0.24 (s, 9 H); MS m/e 230 (31, M+), 215 (64), 141 (43),
73 (100).
Dep r ot ect ion of 1p ′ a n d 1q ′ w it h TBAF . To a stirred
solution of 1p ′ or 1q′ (22.6 mmol) in THF (100 mL) was added
tetrabutylammonium fluoride trihydrate (TBAF) (8.7 g, 27.5
mmol), and the mixture was allowed to stir at room temper-
ature for 3 h. The reaction was quenched with water (50 mL),
the aqueous layer was extracted with Et2O, and the combined
organic layers were washed with brine. After the layers were
dried over Na2SO4, the solvent was removed by distillation at
atmospheric pressure. A mixture of products resulting from
decomposition was recovered by distillation of the residue
under reduced pressure when R2 ) Et, and only very small
amounts (∼0.1 g, 4%) of pure (Z)-2-ethylpent-2-en-4-yn-1-ol 1p
could be isolated as a colorless liquid: bp 39-40 °C/1 mmHg;
3328, 3288 cm-1 1H NMR δ 7.65-7.58 (m, 2 H), 7.40-7.27
;
(m, 3 H), 6.63 (t, J ) 6.7, 1 H), 4.59 (d, J ) 6.7, 2 H), 3.41 (s,
1 H); MS m/e 158 (19, M+), 157 (41), 129 (100), 115 (74).
(Z)-Non -2-en -4-yn -1-ol 1k . The method of Marshall6b was
employed. To a solution of methyl (Z)-non-2-en-4-ynoate24 (4.2
g, 25.1 mmol) in dry ether (270 mL) at -78 °C was added
dropwise a 1 M solution of DIBALH in THF (55 mL, 55 mmol).
After being stirred at -78 °C for 1 h, the reaction was
quenched with water and warmed to room temperature. The
reaction mixture was diluted with Et2O and 10% HCl, and the
layers were separated. The organic layer was washed with
brine, dried (Na2SO4), and evaporated. Column chromatogra-
phy (hexane/AcOEt from 98:2 to 8:2) afforded pure 1k as a
colorless oil (3.3 g, 95%): IR (neat) 3331, 2215, 1020 cm-1; 1H
NMR δ 6.00 (dt, J ) 10.7, 6.3, 1 H), 5.61-5.54 (m, 1 H), 4.38
(dd, J ) 6.3, 1.5, 2 H), 2.34 (td, J ) 6.8, 2.0, 2 H), 1.58-1.36
(m, 4 H), 0.92 (t, J ) 7.3, 3 H); MS m/e 138 (1, M+), 95 (100),
81 (26), 67 (63).
1
IR (neat) 3354, 3293, 1024 cm-1; H NMR δ 5.39-5.36 (m, 1
H), 4.38 (s, 2 H), 3.10 (d, J ) 1.9, 1 H), 2.31-2.21 (m, 2 H),
1.07 (t, J ) 7.5, 3 H); MS m/e 110 (7, M+), 95 (11), 81 (100), 77
(22), 53 (94). On the other hand, column chromatography (9:1
hexane/CH2Cl2) of the residue obtained with R2 ) Ph afforded
directly furan 2q in 93% yield based on 1q′. Deprotection of
the triple bond of 1p ′ (1.0 g, 5.5 mmol) with TBAF (2.05 g, 6.5
mmol) in the absence of added solvent followed by transfer
distillation of the reaction crude gave furan 2p in 94% yield
based on 1p ′.
Cou p lin g betw een Alk -1-yn es a n d (Z)-3-Iod o-2-en -1-
ols. The method of Duboudin21,30 was employed to prepare
2-substituted or 2,3-disubstituted (Z)-3-iodo-2-en-1-ols starting
from propynyl alcohols. (Z)-2-Ethyl-3-iodoprop-2-en-1-ol was
obtained in 80% yield (lit.21 35%) and (Z)-2-phenylprop-2-en-
1-ol in 52% yield (lit.21 39%); crude (Z)-2-ethyl-3-iodo-3-
phenylprop-2-en-1-ol was used directly for the next step
without further purification. The method of Alami31 was
employed for the coupling. To a cooled (0 °C), stirred mixture
of Pd(PPh3)4 (2.9 g, 2.5 mmol) and CuI (0.95 g, 5 mmol) in
pyrrolidine (10 mL) was added a solution of the vinyl iodide
(50 mmol) in pyrrolidine (40 mL), followed by stirring for 5
min. A solution of R4CtCH (100 mmol) in pyrrolidine (10 mL)
was then added dropwise at 0 °C. After being stirred at 0 °C
(R4 ) TMS) or room temperature (R4 ) Bu, Ph) for 2 h (R2 )
Et, R4 ) Bu), 4 h (R2 ) Et, R4 ) TMS; R2 ) Ph, R4 ) Bu; R2
) Et, R3 ) R4 ) Ph), or 5 h (R2 ) Ph, R4 ) TMS), the reaction
mixture was diluted with Et2O and quenched at 0 °C with 10%
HCl. The aqueous layer was extracted with Et2O, and the
combined organic layers were washed with brine, dried (Na2-
SO4), and evaporated. The residue was purified by distillation
or column chromatography. 1l (pale yellow oil, 9:1 hexane/
Oxid a tion w ith Mn O2 follow ed by Gr ign a r d r ea ction .
Dixneuf’s procedure6g was employed. Crude aldehydes obtained
in the first step were reacted with the Grignard reagent
without further purification. Enynols 1c,d were purified as
described.6g Distillation under reduced pressure (83-84 °C/1
mmHg) afforded pure 1i as a pale yellow liquid (66% based
1
on 1f): IR (neat) 3348, 1455 cm-1; H NMR δ 5.57 (dq, J )
8.4, 1.5, 1 H), 4.47 (dt, J ) 8.4, 6.6, 1 H), 2.33 (t, J ) 6.9, 2 H),
1.83 (d, J ) 1.5, 3 H), 1.68-1.35 (m, 6 H), 0.91 (t, J ) 7.3, 6
H); MS m/e 179 (1, M+ - 1), 151 (31), 95 (100). Pure 1j (pale
yellow oil, 81% based on 1f) was recovered by column chro-
matography (9:1 hexane/Et2O): IR (neat) 3347, 2221, 1006
cm-1; 1H NMR δ 7.46-7.40 (m, 2 H), 7.39-7.31 (m, 2 H), 7.30-
7.22 (m, 1 H), 5.77 (distorted dq, J ) 8.7, 1.3, 1 H), 5.72
(distorted d, J ) 8.7, 1 H), 2.39 (t, J ) 6.9, 2 H), 1.86 (d, J )
1.3, 3 H), 1.63-1.39 (m, 4 H), 0.94 (t, J ) 7.2, 3 H); MS m/e
228 (3, M+), 213 (29), 185 (90), 171 (100), 105 (97). (Z)-Enynol
1n was isolated as a pale yellow oil (82% based on 1l) by
column chromatography (9:1 hexane/Et2O): IR (neat) 3364,
1
1461 cm-1; H NMR δ 5.32-5.27 (m, 1 H), 4.60 (dd, J ) 7.7,
6.4, 1 H), 2.28 (td, J ) 6.8, 2.1, 2 H), 2.24-1.92 (m, 2 H), 1.71-
1.30 (m, 6 H), 1.00 (t, J ) 7.3, 3 H), 0.88 (t, J ) 7.3, 3 H), 0.86
(t, J ) 7.3, 3 H); MS m/e 194 (1, M+), 165 (25), 151 (30), 109
(100).
Gen er a l P r oced u r e for Cycloisom er iza tion Rea ction s.
Reactions were carried out on a 3-10 mmol scale based on
(Z)-enynol 1. Solvent, substrate: PdI2 molar ratio, reaction
temperature and time, yield of furans 2 are indicated in Table
1. In a typical experiment, PdI2 and KI (2 mol per mol of pal-
ladium) were added to pure 1 or to a solution of 1 in dry DMA
(27) Marshall, J . A.; DeHoff, B. S. J . Org. Chem. 1986, 51, 863-
872.
(28) Kim, K. D.; Magriotis, P. A. Tetrahedron Lett. 1990, 31, 6137-
6140.
(29) Denis, J . N.; Greene, A. E.; Serra, A. A.; Luche, M. J . J . Org.
Chem. 1986, 51, 46-50.
(30) Duboudin, J . G.; J ousseaume, B. J . Organomet. Chem. 1979,
168, 1-11.
(31) Alami, M.; Ferri, F.; Linstrumelle, G. Tetrahedron Lett. 1993,
34, 6403-6406.