Organic Syntheses, Coll. Vol. 8, p.295 (1993); Vol. 66, p.60 (1988).
Caution! Organoaluminum compounds are pyrophoric. They must be kept and used with caution under a nitrogen atmosphere.
. An oven
-dried, 300-mL, two-necked, round-bottomed flask
equipped with a magnetic stirring bar
, a rubber septum inlet, and an outlet connected to a mercury bubbler
is flushed with nitrogen
, immersed in a water bath
kept at room temperature, and charged with 22.6 mL (125 mmol) of 1-decyne (Note 1)
and 80 mL of hexane (Note 2)
. To this flask is added dropwise, with stirring, 22.3 mL (125 mmol) of diisobutylaluminum hydride (Note 3)
using a syringe (Note 4)
. After the addition has been completed, the water bath is replaced with an oil bath
kept at 50–60°C, and the reaction mixture is stirred for 6 hr at this temperature (Note 5)
B. (5Z, 7E)-5,7-Hexadecadiene.
To a mixture of 21.0 g (100 mmol) of (Z)-1-hexenyl iodide (Note 6)
, 13.6 g (100 mmol) of zinc chloride (Note 7)
, and 1.15 g (1 mmol) of tetrakis(triphenylphosphine)palladium (Note 8)
in 100 mL of tetrahydrofuran (Note 9)
is added the solution of (E)-1-decenyldiisobutylalane
prepared as described above, while the reaction temperature is controlled with a water bath at room temperature. After the reaction mixture is stirred for 6 hr at room temperature, it is slowly transferred into a mixture of 300 mL of ice-cooled 3 N hydrochloric acid
and 100 mL of pentane
via a double-ended needle under a positive pressure of nitrogen
. The organic layer is separated, and the aqueous layer is extracted twice with 100 mL of pentane
. The combined organic layer is washed with 100 mL of water, followed by 100 mL of saturated aqueous sodium bicarbonate
, and then dried over anhydrous magnesium sulfate
. After filtration, the solvent is removed using a rotary evaporator
. Hydroquinone (30 mg)
is added and the residue is distilled (Note 10)
to give 14.3–15.8 g
based on (Z)-1-hexenyl iodide
] of (5Z,7E)-5,7-hexadecadiene
as a colorless liquid, bp 116–119°C (1 mm) (Note 11)
and (Note 12)
The submitters used 1-decyne from Farchan Laboratories, Inc.
without further purification. The checkers used the material purchased from Aldrich Chemical Company, Inc. and Tokyo Kasei Kogyo Company.
The submitters used neat diisobutylaluminum hydride obtained from Ethyl Corporation
. The checkers used the material from Aldrich Chemical Company, Inc.
The submitters used a 50-mL syringe with a Luer-lock and a long (≥6-in.) 18-gauge needle, the plunger of which was lightly greased with a silicone grease. For a larger-scale operation, it is advisable to use a septum-capped graduated cylinder and a double-ended needle in place of a syringe.
Zinc chloride available from Mallinckrodt, Inc.
was flame-dried under a slow stream of nitrogen
. The checkers used the material from Wako Pure Chemical Industries, Ltd. after heating under vacuum (1 mm).
was added to avoid polymerization of the diene product.
Gas chromatographic examination of the reaction mixture using a 2-ft column of 20% SE-30 on Chromosorb W
as an internal standard (200°C) indicates that (5Z,7E)-5,7-hexadecadiene
is formed in 86–90%
yield, based on (Z)-1-hexenyl iodide
. The product obtained by this procedure shows the following properties: nD23
1.4662; IR (neat) cm−1
: 1630 (w), 1370 (w), 978 (m), 943 (m), 720 (m); 1
H NMR [CCl4
Si] δ: 0.8–1.0 (m, 6 H), 1.15–1.5 (m, 16 H), 1.9–2.3 (m, 4 H) m, 5.15 (dt, 1 H, J
= 10, 8), 5.61 (dt, 1 H, J
= 14, 7) 5.92 (dd, 1 H, J
= 10, 11), 6.30 (dd, 1 H, J
= 11, 14).
can be prepared in the same manner as described except that (E)-1-hexenyl iodide
is used in place of its (Z
) isomer. The (E
) iodide is obtainable by treating (E)-1-hexenyldiisobutylalane
, prepared from 1-hexyne
and diisobutylaluminum hydride
, with iodine
) diene prepared by this procedure shows the following properties: nD23
1.4671; IR (neat) cm−1
: 1370 (w), 982 (m), 722 (m); 1
H NMR [CCl4
Si] δ: 0.89 (t, 6 H, J
= 6), 1.15–1.7 (m, 16 H), 1.8–2.2 (m, 4 H), 5.2–6.15 (m, 4 H): 13
C NMR [CDCl3
Si] δ: 13.93, 14.06, 22.34, 22.76, 29.40, 29.62, 31.16, 31.78, 32.03, 32.37, 32.72, 130.59, 132.19, 132.26.
The procedure described here is based on two reports by Negishi and his co-workers.5,6
The original procedure5
did not use zinc chloride
as the second catalyst and required ca. 5 mol% of Pd(PPh3)4
. The preparation of (E
)-1-alkenylalane via hydroalumination was first reported by Wilke and Müller.7
The procedure used here is essentially that which was described by Zweifel.8
The first highly stereoselective and satisfactory syntheses of conjugated dienes of general applicability are those based on organoboron chemistry reported by Negishi for (E,E
as well as by Zweifel for (Z,Z
The method described here represents the first highly selective and general cross-coupling procedure for preparing conjugated dienes.5,6
Subsequently, several variations of the above-described method have been published by Negishi and others. Some salient features of these investigations are as follows. First, palladium–phosphine complexes, such as Pd(PPh3
, are preferred to nickel complexes,5
which tend to reduce stereoselectivity. Second, all three possible stereoisomers may be prepared using this methodology. Third, in addition to Al, Zr,12
have been shown to participate in Pd-catalyzed alkenyl–alkenyl cross-coupling. Fourth, the reaction is markedly accelerated by the addition of zinc and cadmium halides, such as ZnCl2
, and CdCl2
at least in cases where organometals containing Al,6
are used. This and other observations suggest that alkenylzinc derivatives are probably the most reactive organometals in this reaction,6
although no systematic comparisons have been made so far. Otherwise, the choice of metal depends on the stereochemistry of the desired product the required chemoselectivity, and other factors. For example, (E
)-alkenyl metals are most directly available via hydroalumination,8
of alkynes. In cases where the use of such derivatives is desirable, Al. B. or Zr should be considered first. On the other hand, (Z
)-alkenyl metals are often readily available via carbocupration21
of alkynes, and they may be used directly or via formation of the corresponding (Z
Together with the organoboron procedures mentioned above, the Pd-catalyzed cross coupling procedures have been applied to the synthesis of a wide variety of insect pheromones, terpenoids, and carotenoids.
Chemical Abstracts Nomenclature (Collective Index Number);
hydrochloric acid (7647-01-0)
sodium bicarbonate (144-55-8)
zinc chloride (7646-85-7)
magnesium sulfate (7487-88-9)
calcium hydride (7789-78-8)
diisobutylaluminum hydride (1191-15-7)
(Z)-1-hexenyl iodide (16538-47-9)
5,7-Hexadecadiene, (Z, E)- (86883-79-6)
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