Org. Synth. 1992, 70, 215
DOI: 10.15227/orgsyn.070.0215
ALKYNYL(PHENYL)IODONIUM TOSYLATES: PREPARATION AND STEREOSPECIFIC COUPLING WITH VINYLCOPPER REAGENTS. FORMATION OF CONJUGATED ENYNES. 1-HEXYNYL(PHENYL)IODONIUM TOSYLATE AND (E)-5-PHENYLDODEC-5-EN-7-YNE
[Iodine, 1-hexynyl(4-methylbenzenesulfonato-O)phenyl- and Benzene, (1-butyl-1-octen-3-ynyl)-, (E)-]
Submitted by Peter J. Stang and Tsugio Kitamura
1.
Checked by Kazuaki Ishihara and Hisashi Yamamoto.
1. Procedure
A. 1-Trimethylsilyl-1-hexyne (Note 1). A dry, 500-mL, three-necked, round-bottomed flask (equipped with a magnetic stirrer system) is fitted with one 50-mL and one 125-mL pressure-equalizing addition funnel and a reflux condenser. The top of the condenser is mounted with a T-piece connected at one end to an argon outlet and at the other end to an oil bubbler. The apparatus is purged with dry argon and the reaction is carried out under an argon atmosphere. The flask is charged with 16.4 g (0.20 mol) of 1-hexyne (Note 2) and 200 mL of tetrahydrofuran (THF, (Note 3)), and the mixture is cooled to approximately −70°C with a dry ice-2-propanol slush bath. The 125-mL dropping funnel is filled with 80 mL (0.20 mol) of 1.63 M butyllithium in hexane (Note 4) which is added over a period of 30 min to the stirred, cold (−70°C) 1-hexyne in THF. After addition is complete the flask is gradually warmed over a 3-hr period to −20°C, then recooled to −70°C with the dry ice-2-propanol slush bath. Chlorotrimethylsilane (Note 5), 25.3 mL (0.20 mol), is placed in the 50-mL dropping funnel and added over a period of 15 min to the stirred, cooled reaction mixture. After the addition is complete the slush bath is removed and the mixture is first stirred at room temperature for 16 hr, then heated under reflux for 1 hr (Note 6). The mixture is cooled to 0°C with an ice-water bath and then 50 mL of water is carefully added. The entire reaction mixture is transferred to a 1-L separatory funnel and extracted with 200 mL of pentane. The organic phase is separated, washed successively with three 100-mL portions of water followed by 100 mL of saturated sodium chloride solution and then dried over anhydrous magnesium sulfate. After filtration the solvent is distilled off through a 15-cm Vigreux column. The pale yellow residue is transferred to a 100-mL round-bottomed flask and distilled through a 15-cm Vigreux column to give 25.0–27.5 g (81–89%) of 1-trimethylsilyl-1-hexyne as a clear, colorless liquid, bp 149–156°C, that can be used as is in the subsequent step.
B. 1-Hexynyl(phenyl)iodonium tosylate. The center neck of a dry, 500-mL, three-necked, round-bottomed flask (equipped with a magnetic stirrer system) is fitted with a 50-mL pressure-equalizing addition funnel One side neck is fitted with a glass stopper and the other with a gas inlet to which is attached a T-piece connected to an argon supply and an oil bubbler. After the flask is purged with dry argon, it is charged with 22.0 g (0.10 mol) of finely ground iodosobenzene (Note 7), 200 mL of chloroform (Note 8) and 17.0 g (0.11 mol) of 1-trimethylsilyl-1-hexyne, and the entire mixture is cooled to 0°C with an ice-water bath. Boron trifluoride etherate (Note 9), 13.0 mL (0.11 mol), is added dropwise over a period of about 5 min to the stirred, cooled reaction mixture (Note 10). After the addition is complete the mixture is stirred at room temperature for about 16 hr (Note 11).
To a 1-L beaker are added 76.1 g (0.4 mol) of p-toluenesulfonic acid monohydrate (Note 12) and 400 mL of water. To this solution is carefully added 21.2 g (0.2 mol) of anhydrous sodium carbonate and then the entire solution is purged with argon for about 15 min to replace all air. This solution of sodium toluenesulfonate (NaOTs), along with the contents of the reaction flask, are placed in a 1-L separatory funnel and the mixture is vigorously shaken for a period of about 10 min (Note 13). The organic phase is separated and the aqueous phase is extracted with 50 mL of methylene chloride. The combined organic phases are dried over anhydrous magnesium sulfate, filtered and the solvent evaporated on a rotary evaporator. To the residual yellow-brown oil is added a mixture of 75 mL of diethyl ether and 75 mL of pentane resulting, after stirring, in fine white crystals. The powdery white crystals are filtered, washed with two 50-mL portions of a diethyl ether/pentane (1:1 v/v) mixture, air dried, then dried under reduced pressure. The resulting white crystalline solid, 27–34 g (60–75%), mp 77–80°C, (dec) is essentially pure and ready for most uses (Note 14).
C. (E)-5-Phenyldodec-5-en-7-yne.
CAUTION: Dimethyl sulfide is a volatile, very smelly irritant. This reaction must be conducted in a hood!
A dry, 100-mL, three-necked, round-bottomed flask (equipped with a magnetic stirrer system) is fitted with a 25-cm Liebig condenser, a 25-mL pressure-equalizing dropping funnel topped off with a gas-inlet, and a glass stopper. After the flask is purged with argon, it is charged with 0.90 g (37.5 mmol) of magnesium turnings and 15 mL of anhydrous ether. To the dropping funnel is added a solution of 4.0 mL (37.5 mmol) of 1-bromobutane (Note 15) in 20 mL of anhydrous ether. This solution is added to the reaction flask at such a rate (approximately 1 hr) that after the Grignard reaction is initiated a gentle reflux is maintained. After the addition is complete the mixture is stirred for an additional 30 min.
The center neck of a dry, 250-mL, three-necked, round-bottomed flask (equipped with a magnetic stirrer system) is fitted with a 50-mL pressure-equalizing dropping funnel topped off with a rubber septum and an argon inlet. The side necks are fitted with a glass stopper and a rubber septum, respectively. The apparatus is purged with argon and to the flask are added 7.7 g (37.5 mmol) of copper(I) bromide-dimethyl sulfide complex (Note 16), 60 mL of anhydrous ether, and 38 mL of dimethyl sulfide (Note 17). The mixture is cooled to −70°C with a dry ice-2-propanol slush bath. The previously prepared butyl Grignard reagent is transferred to the addition funnel via a double-ended needle with a positive argon pressure. The Grignard reagent is added dropwise, over a 30-min period, to the cooled reaction mixture (Note 18). After the addition is complete the reaction is maintained between −40°C to −50°C for 2 hr, then recooled to −70°C. Phenylacetylene (Note 19), 4.1 mL (37.1 mmol), is slowly added via a syringe through the rubber septum. After addition, the reaction mixture is maintained at −30°C to −25°C for 2 hr (Note 20), then recooled to −70°C and 6.8 g (15 mmol) of the previously prepared iodonium tosylate is added, in the solid form, through the side neck, over a positive argon pressure. The stirring reaction mixture is gradually warmed to room temperature and stirred for an additional 12 hr at room temperature. The mixture is poured into a 1-L beaker containing 200 mL of saturated ammonium chloride solution and stirred vigorously. The undissolved materials are filtered off and the organic phase is separated. The aqueous phase is extracted with three 50-mL portions of ether. The combined organic phase are washed with 100 mL of water followed by 100 mL of saturated sodium chloride solution, and dried over anhydrous magnesium sulfate and filtered. The solvent is removed on a rotary evaporator in the hood and the residual oil chromatographed (4 × 50 cm column) on alumina (600 g, (Note 21)). The column is successively eluted with 1 L of hexane, 750 mL of 10% dichloromethane-hexane, 500 mL of 20% dichloromethane-hexane and 250 mL of 30% dichloromethane-hexane. The fractions are analyzed by TLC on silica gel (Note 22) using 10% dichloromethane-hexane as eluent and the product-containing fractions (Note 23) are combined. The solvent is evaporated on a rotary evaporator and the residual yellow-brown oil (5.8 g) (Note 24) is distilled under reduced pressure, bp 135–143°C (3–4 mm), to give 2.3 g of crude product. Redistillation under reduced pressure affords 1.9–2.1 g (53–58%) of product as a pale yellow liquid, bp 143–144°C (1 mm) (Note 25).
2. Notes
1.
Many 1-trimethylsilylalkynes are commercially available from Aldrich, Petrarch and other vendors of silicon compounds. Alternatively they are readily made from 1-alkynes and
chlorotrimethylsilane as described in part A.
2.
1-Hexyne was obtained from Tokyo Kasei Kogyo Co., Ltd. or Aldrich Chemical Company, Inc. and used without purification.
3.
Tetrahydrofuran was obtained from Wako Pure Chemical Industries, Ltd., and distilled from
potassium benzophenone ketyl immediately before use.
4.
Butyllithium in hexane (2.6 M) was obtained from Mitsuwas Pure Chemical or Aldrich Chemical Company, Inc. and a freshly opened sample was used without assay or purification.
5.
Chlorotrimethylsilane was obtained from Shin-ETSU Silicon Chemicals or PCR Research Chemicals, Inc., and distilled prior to use.
6.
During this period copious amounts of a white precipitate
(LiCl) is formed.
7.
Iodosobenzene was purchased by the checkers from Tokyo Kasei Kogyo Co., Ltd. and dried under reduced pressure prior to use.
8.
Chloroform was distilled from
phosphorus oxide (P2O5) and passed through an alumina column prior to use.
9.
Boron trifluoride etherate (98%) was obtained from Wako Pure Chemical Industries, Ltd., or MC and B Manufacturing Chemists, and distilled from granular
calcium hydride prior to use.
10.
The pale yellow suspension turns to a deeper yellow suspension during addition.
11.
Iodosobenzene is a polymer and depolymerizes as it reacts, forming a clear, yellow-light brown, homogeneous solution during the course of the reaction. It is not ready for work-up until a clear homogeneous solution is obtained.
12.
p-Toluenesulfonic acid monohydrate was obtained from Wako Pure Chemical Industries, Ltd., or MC and B Manufacturing Chemists, and used without further purification.
13.
Care must be taken to release periodically the pressure formed. It is advisable to chill both solutions prior to mixing and shaking.
14.
The spectral properties of
1-hexynyl(phenyl)iodonium tosylate are as follows: IR (nujol) cm
−1: 2185 (m, C≡C), 1225 (s), 1175 (m), 1145 (vs), 1115 (m), 1025 (m), 1000 (s), 985 (m, sh), 807 (m), 730 (m), 675 (s); FAB-MS m/z 285 (n, BuC≡CIPh
+);
1H NMR (CDCl
3) δ 0.73–0.92 (m, CH
3), 1.12–1.58 (m, CH
2CH
2), 2.30 (s, ArCH
3), 2.30–2.50 (m, CH
2), 6.98–7.60 (m, ArH), 7.92–8.05 (m, ArH).
15.
1-Bromobutane was obtained from Wako Pure Chemical Industries, Ltd., or Eastman Kodak Company, and distilled through a
10-cm Vigreux column prior to use.
16.
Copper(I) bromide-dimethyl sulfide complex, (CuBr·SMe2), 99%, was obtained from Aldrich Chemical Company, Inc. and purified prior to use as follows:
10 g of CuBr·SMe2 was dissolved in
20 mL of dimethyl sulfide and triturated with
30 mL of pentane. The resulting white crystals were filtered, washed with three
20-mL portions of pentane and dried under reduced pressure.
17.
Dimethyl sulfide, 99+%, anhydrous, was obtained from Tokyo Kasei Kogyo Co., Ltd., or Aldrich Chemical Company, Inc.18.
The white suspension turned to an orange suspension during the course of the addition.
19.
Phenylacetylene was obtained from Tokyo Kasei Kogyo Co., Ltd., or Farchan Laboratories and distilled through a 15-cm Vigreux column prior to use.
20.
During this period the color changed from orange through brown to black.
21.
Unactivated alumina from J. T. Baker Chemical Company was used.
22.
TLC
silica gel 60F254 sheets were obtained from Merck & Company, Inc.23.
The desired product appears as the second spot on TLC with an R
f = 0.42–0.45 with
10% dichloromethane-hexane.
24.
The major by-product is
5,8-diphenyldodeca-5,7-diene, which can be separated by distillation.
25.
GC analysis of the product on a 10% UCW-982 Chromosorb W column (0.25 in × 6 ft) at 200°C showed a single isomer with a purity of 99%. The spectral properties of the product are as follows: IR (neat) cm
−1: 3070 (m, sh), 3050 (m), 3015 (m), 2950 (vs), 2925 (vs), 2855 (s), 2200 (w), 1595 (m), 1570 (w), 1490 (m), 1465 (s), 1442 (s), 1375 (m), 1325 (m), 847 (m), 752 (vs), 690 (vs), MS (EI) m/z: 240 M
+, 57%, 141 (100%), 105 (53%);
1H NMR (CDCl
3) δ 0.81–1.00 (m, CH
3), 1.21–1.59 (m, CH
2CH
2), 2.30–2.46 (m, CH
2), 2.67–2.84 (m, CH
2), 5.74 (t, J = 2, C=CH), 7.14–7.51 (m, ArH):
13C NMR (300 MHz, CDCl
3) δ 13.52 (CH
3), 13.81 (CH
3), 19.35 (CH
2), 21.91 (CH
2), 22.50 (CH
2), 30.50 (CH
2) 30.96 (CH
2), 31.70 (CH
2), 78.93 (C≡C), 95.47 (C≡C), 107.42 (C=CH), 125.78, 127.44, 128.24, 140.52 (aromatic), 151.88 (C=CH).
Handling and Disposal of Hazardous Chemicals
The procedures in this article are intended for use only by persons with prior training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011 www.nap.edu). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see Chapter 8 of Prudent Practices.
These procedures must be conducted at one's own risk. Organic Syntheses, Inc., its Editors, and its Board of Directors do not warrant or guarantee the safety of individuals using these procedures and hereby disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedures herein.
3. Discussion
The only known alternative procedure for the preparation of alkynyl(phenyl)iodonium arylsulfonates, the latest member of the family
2 of polyvalent iodine compounds, involves the reaction of [hydroxy(tosyloxy)iodo]benzene, PhIOH·OTs, with terminal alkynes as first reported by Koser
3 and elaborated by us.
4 This procedure has a number of shortcomings. Formation of the desired alkynyliodonium salt is usually accompanied by a related vinyl species, R(TsO)C=CHIPh·OTs, that both decreases the yields and causes purification problems. Furthermore, when the alkyl substituent of the starting alkyne is small, such as CH
3, n-Pr, n-Bu, etc., this procedure gives either no product
3 or low yields
4 at best.
The present procedure, similar to that of Fujita
5 for the preparation of alkynyl(phenyl)iodonium tetrafluoroborates, RC≡CIPh·BF
4, is simpler, much more general and in most cases gives significantly better yields.
6 Table I gives yields of alkynyl(phenyl)iodonium sulfonates prepared by this procedure.
TABLE I
ALKYNYL(PHENYL)IODONIUM SULFONATES
|
|
Starting Alkyne
|
Product
|
Yields (%)
|
M.P. (dec.) °C
|
|
|
CH3C≡CH
|
CH3C≡CIPh·OTs
|
62
|
123–125
|
|
EtC≡CH
|
EtC≡CIPh·OTs
|
81
|
108–110
|
|
n-PrC≡CH
|
n-PrC≡CIPh·OTs
|
89
|
93–95
|
|
Me3SiC≡CSiMe3
|
Me3SiC≡CIPh·OTs
|
70
|
107–109
|
|
PhC≡CH
|
PhC≡CIPh·OTs
|
61
|
128–1334
|
|
t-BuC≡CH
|
t-BuC≡CIPh·OTs
|
67
|
118–1244
|
|
Alkynyl(phenyl)iodonium sulfonates are stable, microcrystalline substances that can be stored and used indefinitely with little or no decomposition. They have been employed in the formation of aryl (2-furyl)iodonium tosylates,
7 alkynyl sulfonate,
4 carboxylate
8 and phosphate
9 esters, tricoordinate vinyliodinane species,
10 and alkylidenecarbene-iodonium ylides.
11The stereoselective formation of conjugated enynes has been reported
12 via the coupling of vinylcopper reagents with alkynyl(phenyl)iodonium tosylates. A representative example of this process is described in part C of the present procedure. This method
12 affords stereoisomerically pure 1,1-disubstituted conjugated 1,3-enynes with a trisubstituted olefin component with complete control of olefin geometry. The simplicity of the procedure, mild reaction conditions, reasonable yields (46–94%) and total stereocontrol
12 should make this an attractive alternative and complement to the known
13,14 Pd-catalyzed olefin-alkyne couplings for the synthesis of this important class of aliphatic compounds.
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
potassium benzophenone ketyl
(LiCl)
CH3C≡CH
CH3C≡CIPh·OTs
EtC≡CH
n-PrC≡CH
n-PrC≡CIPh·OTs
Me3SiC≡CSiMe3
PhC≡CH
PhC≡CIPh·OTs
t-BuC≡CH
t-BuC≡CIPh·OTs
Iodine, 1-hexynyl(4-methylbenzenesulfonato-O)phenyl-
ether,
diethyl ether (60-29-7)
ammonium chloride (12125-02-9)
chloroform (67-66-3)
magnesium turnings (7439-95-4)
sodium chloride (7647-14-5)
sodium carbonate (497-19-8)
1-bromobutane (109-65-9)
Pentane (109-66-0)
methylene chloride,
dichloromethane (75-09-2)
Phenylacetylene (536-74-3)
magnesium sulfate (7487-88-9)
dimethyl sulfide (75-18-3)
butyllithium (109-72-8)
Tetrahydrofuran,
THF (109-99-9)
Iodosobenzene (536-80-1)
hexane (110-54-3)
1-Hexyne (693-02-7)
argon (7440-37-1)
boron trifluoride etherate (109-63-7)
calcium hydride (7789-78-8)
CHLOROTRIMETHYLSILANE (75-77-4)
phosphorus oxide (1314-56-3)
p-toluenesulfonic acid monohydrate (6192-52-5)
1-Trimethylsilyl-1-hexyne (3844-94-8)
1-Hexynyl(phenyl)iodonium tosylate (94957-42-3)
(E)-5-Phenyldodec-5-en-7-yne,
Benzene, (1-butyl-1-octen-3-ynyl)-, (E)- (111525-79-2)
sodium toluenesulfonate
iodonium tosylate
5,8-diphenyldodeca-5,7-diene
copper(I) bromide-dimethyl sulfide complex (54678-23-8)
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