SYNTHESIS
July 1998
1017
Undeca-2,5-diyn-1-ol (2c): Rf 0.78 (Et2O/petroleum ether 4:6).
1H NMR: δ = 0.87 (3H, t, J = 4.96 Hz), 1.22–1.59 (6H, m), 2.12 (2H,
m), 3.17 (2H, quint, J = 2.26 Hz), 4.24 (2H, bs).
13C NMR: δ = 9.7, 15.3, 18.6, 22.1, 28.3, 31.0, 50.9, 73.3, 78.3, 80.5,
81.1.
1H NMR: δ = 0.87 (3H, t, J = 6.70 Hz), 1.27–1.69 (10H, m), 2.14 (4H,
m), 2.31 (2H, t, J = 7.35 Hz), 3.11 (4H, bs), 3.65 (3H, s).
13C NMR: δ = 9.7, 13.9, 18.2, 18.6, 22.1, 24.1, 24.4, 26.9, 27.2, 36.2,
54.4, 79.3, 79.9 (2C), 80.6 (2C), 80.8, 176.8.
IR (film): ν = 2260, 1733, 1215 cm–1.
IR (film): ν = 3381, 2860, 2209 cm–1.
MS (70 eV): m/z (%) = 107 (23), 95 (99), 93 (25), 79 (100), 77 (82),
55 (56), 43 (22).
Methyl (6Z,9Z,12Z)-Octadeca-6,9,12-trienoate (6):
Nickel acetate tetrahydrate (3.0 g, 12 mmol) was dissolved in 95%
EtOH (130 mL) and placed under H2. 1 M NaBH4 in abs EtOH
(12 mL) was added at r.t., followed, after 30 min, by ethylenediamine
(3.2 mL, 48 mmol) and triyne 5 (3.48 g, 12 mmol) diluted in EtOH
(20 mL). The reaction was monitored by TLC, and quenched by ad-
dition of Et2O (100 mL) and filtration through a pad of Celite. The or-
ganic extract was washed with brine, dried (MgSO4), and
concentrated. Flash chromatography of the residue (Et2O/petroleum
ether 5:95 to 50:50) afford pure Z,Z,Z-triene (65% yield); Rf 0.73
(Et2O/petroleum ether 1:9).
Methyl 10-Hydroxydeca-5,8-diynoate (2d): Rf 0.14 (Et2O/petroleum
ether 4:6).
1H NMR: δ = 1.79 (2H, quint, J = 7.35 Hz), 1.92 (1H, t, J = 2.26 Hz),
2.20 (2H, m), 2.42 (2H, t, J = 7.39 Hz), 3.16 (2H, quint, J = 2.24 Hz),
3.66, (3H, s), 4.24 (2H, bs).
13C NMR: δ = 9.3, 17.7, 23.5, 32.5, 50.3, 51.3, 74.3, 78.5, 79.3, 79.5,
173.6.
IR (film): ν = 3444, 2860, 1735, 1215 cm–1.
MS (70eV): m/z (%) = 69 (85), 51 (21), 41 (100), 37 (10).
1H NMR: δ = 0.81 (3H, t, J = 6.79 Hz), 1.18–1.30 (8H, m), 1.55–1.70
(2H, m), 1.98–2.11 (4H, m), 2.29 (2H, t, J = 7.26 Hz), 2.78 (4H, t, J
= 5.34 Hz), 3.65 (3H, s), 5.27–5.41 (6H, m).
Methyl 11-Hydroxyundeca-6,9-diynoate (2e): Rf 0.12 (Et2O/petro-
leum ether 4:6).
13C NMR: δ = 14.2, 22.6, 24.5, 25.6, 26.8, 27.1, 29.0, 29.4, 29.7, 31.2,
34.2, 50.1, 127.5, 128.1, 128.2, 128.4, 129.4, 130.2, 173.4.
IR (film): ν = 1738, 1658, 1259 cm–1.
1H NMR: δ = 1.42–1.82 (4H, m), 2.17 (2H, m), 2.32 (2H, t, J = 7.40
Hz), 3.15 (2H, quint, J = 2.28 Hz), 3.65 (3H, s), 4.24 (2H, t, J = 2.20
Hz).
MS (70 eV): m/z (%) = 116 (12), 113 (27), 112 (14), 101 (30), 87 (66),
84 (17), 74 (45), 67 (39), 59 (100), 57 (32), 56 (16), 55 (77), 44 (20),
43 (71), 42 (21), 41 (62), 39 (28).
13C NMR: δ = 9.2, 17.8, 23.6, 27.6, 33.0, 49.9, 51.1, 78.6 (2C), 79.1,
79.7, 173.6.
IR (film): ν = 3406, 2878, 1734, 1215 cm–1.
(6Z,9Z,12Z)-Octadeca-6,9,12-trienoic Acid (γ-Linolenic Acid):
To a 0°C solution of methyl ester 6 in THF (80 mL) was added drop-
wise 0.5 N aq LiOH (134 mL). After 30 min, the mixture was brought
to r.t. and stirred for 12 h. The solution was acidified to pH 2 with 1 N
HCl, and extracted with Et2O. The combined Et2O extracts were dried
(MgSO4) and concentrated to furnish γ-linolenic acid (98% yield); Rf
0.43 (Et2O/petroleum ether 4:6).
Methyl 14-Hydroxytetradeca-9,12-diynoate (2f): Rf 0.21 (Et2O/petro-
leum ether 4:6).
1H NMR: δ = 1.21–1.78 (10H, m), 2.18 (2H, m), 2.30 (2H, t, J = 7.34
Hz), 3.16 (2H, quint, J = 2.30 Hz), 3.61 (3H, s), 4.22 (2H, t, J = 2.30
Hz).
13C NMR: δ = 9.8, 15.1, 24.7, 28.3, 28.5, 28.7 (2C), 28.9, 34.0, 50.5,
51.5, 78.6, 79.0, 80.1, 80.8, 174.5.
1H NMR: δ = 0.86 (3H, t, J = 6.79 Hz), 1.13–1.30 (8H, m), 1.55–1.70
(2H, m), 1.93–2.06 (4H, m), 2.28 (2H, t, J = 7.24 Hz), 2.78, (4H, t, J
= 5.34 Hz), 5.17–5.43 (6H, m).
IR (film): ν = 3442, 2931, 2364, 1736 cm–1.
13C NMR: δ = 14.1, 22.6, 24.6, 25.6, 26.9, 27.2, 29.1, 29.4, 29.7, 31.6,
34.2, 127.6, 128.1, 128.2, 128.4, 129.6, 130.4, 173.6.
3-Hydroxymethyl-6-methoxyhexa-1,2-dien-4-yne (3a): Rf 0.14 (Et2O/
petroleum ether 4:6).
1H NMR: δ = 3.35 (3H, s), 4.06 (2H, t, J = 2.15 Hz), 4.27 (2H, bs),
4.75 (2H, t, J = 2.81 Hz).
IR (film): ν = 1725, 1654 cm–1.
13C NMR: δ = 57.1, 59.5, 65.9, 77.1, 84.7, 91.1, 91.3, 210.1.
IR (film): ν = 3288, 2361 2337, 1926 cm–1.
We are indebted to the “Service des Molécules Marquées” (Dr J.-P.
Noel and Dr A. Vandais, CEA Saclay) for analyses and to the CNRS
and MESR for financial support.
Methyl 11-Bromoundeca-6,9-diynoate (4):
To a solution of methyl 11-hydroxyundeca-6,9-diynoate (2e) (22.3 g,
107.2 mmol) and CBr4 (49.8 g, 150.1 mmol) in CH2Cl2 (360 mL) at
0°C was added under argon PPh3 (39.4 g, 150.1 mmol) over a period
of 1 h. After 5 min the mixture was brought to r.t. and stirred for 1 h.
CH2Cl2 was evaporated then the residue was diluted with Et2O and
filtered through a pad of Celite and concentrated. Chromatography
(Et2O/petroleum ether 1:9 to 4:6) provided the diyne 4 in 92% yield;
Rf 0.57 (Et2O/petroleum ether 4:6).
(1) Beerthuis, R. K.; Nugteren, D. H.; Pabon, H. J. J.; Van Dorp, D.
A. Rec. Trav. Chim. 1968, 87, 461.
Kunau, W. H. Angew. Chem., Int. Ed. Engl. 1976, 15, 61.
Guarnieri, M.; Johnson, R. M. Adv. Lipid Res. 1970, 8, 115.
(2) Coleman, R. Biochim. Biophys. Acta 1973, 300, 1.
(3) Viala, J.; Santelli, M. J. Org. Chem. 1988, 53, 6121.
Viala, J.; Santelli, M. Synthesis 1988, 395.
(4) Viala, J.; Munier, P.; Santelli, M. Tetrahedron 1991, 47, 3347.
(5) Sandri, J.; Viala, J. J. Org. Chem. 1995, 60, 6627.
(6) Sprecher, M. Prog. Chem. Fats Other Lipids 1978, 15, 219.
(7) Nicolaou, K. C.; Ladduwahetty, T.; Elisseou, E. M. J. Chem.
Soc., Chem. Commun. 1985, 1580.
1H NMR: δ = 1.46–1.77 (4H, m), 2.17 (2H, m), 2.31 (2H, t, J =
7.36 Hz), 3.18 (2H, quint, J = 2.33 Hz), 3.65 (3H, s), 3.89 (2H, t, J =
2.36 Hz).
13C NMR: δ = 8.5, 13.5, 16.9, 22.6, 26.6, 32.0, 49.9, 71.9, 73.9, 79.1,
80.5, 172.1.
IR (film): ν = 2260, 1734, 1215, 750 cm–1.
(8) Similar results have been reported, see Morel, J. M.; Gaudin, C.
Tetrahedron Lett. 1991, 32, 5749.
Methyl Octadeca-6,9,12-triynoate (5):
(9) Mori, K.; Takeuchi, T. Liebigs Ann. Chem. 1989, 453.
Ward, J. P.; Van Dorp, D. A. Recl. Trav. Chim. Pays Bas 1965,
85, 117.
This was prepared from methyl 11-bromoundeca-6,9-diynoate (4)
and hept-1-yne in a similar manner as for the general procedure, but
the mixture was stirred overnight at 40°C. Workup and chromatogra-
phy (Et2O/petroleum ether 1:9 to 4:6) afforded the triyne in 89%
yield; Rf 0.40 (Et2O/petroleum ether 1:9).
Pleshakov, M. G. J. Gen. Chem. USSR (Engl. Transl.) 1960, 30,
2955.