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Org. Synth. 1995, 72, 180
DOI: 10.15227/orgsyn.072.0180
PREPARATION AND REACTIONS OF ALKENYLCHROMIUM REAGENTS: 2-HEXYL-5-PHENYL-1-PENTEN-3-OL
Submitted by Kazuhiko Takai1, Koichi Sakogawa, Yasutaka Kataoka, Koichiro Oshima, and Kiitiro Utimoto2.
Checked by Tadahiro Takemoto and Larry E. Overman.
1. Procedure
A. 1-Hexylethenyl triflate (Note 1). A dry, 300-mL, three-necked, round-bottomed flask is equipped with a magnetic stirring bar, nitrogen inlet, rubber septum, and a 100-mL, graduated, pressure-equalizing addition funnel that is sealed with a rubber septum. The flask is charged with 1-octyne (11 g, 0.10 mol, (Note 2)) and dry hexane (100 mL, (Note 3)). The contents of the flask are cooled to −30°C (dry ice-methanol). The addition funnel is charged with neat trifluoromethanesulfonic acid (TfOH, 4.9 mL, 55 mmol, (Note 4)) which is then added dropwise at −30°C to the stirring solution over a period of 30 min. The addition funnel is rinsed with dry hexane (10 mL). The dark brown solution is warmed to 0°C and stirred at 0°C for 10 min. Saturated sodium bicarbonate (NaHCO3) solution (20 mL) is introduced at 0°C to the reaction mixture. The organic layer is separated, washed with additional NaHCO3 solution (2 × 50 mL), and then dried over potassium carbonate. The solvent is removed with a rotary evaporator. The crude product is distilled using a short-path still to give 9.6–10.4 g (67–73%) of 1-hexylethenyl triflate (Note 5), bp 97–98°C at 19 mm.
B. 2-Hexyl-5-phenyl-1-penten-3-ol. A dry, 500-mL, four-necked, round-bottomed flask is equipped with a mechanical stirring bar, nitrogen inlet, rubber septum, and a 100-mL, graduated, pressure-equalizing addition funnel that is sealed with a rubber septum. In the flask are placed anhydrous chromium(II) chloride (CrCl2) (10 g, 80 mmol, (Note 6)) and anhydrous nickel(II) chloride (NiCl2) (52 mg, 0.40 mmol, (Note 7)) under an argon atmosphere. The flask is cooled to 0°C and dry, oxygen-free N,N-dimethylformamide (DMF, 250 mL, (Note 8)) is added to the flask with stirring. The salts are dissolved in a slightly exothermic process. The mixture is stirred at 0°C for 10 min. To the CrCl2-NiCl2 reagent at 25°C is added a solution of 3-phenylpropanal (2.7 g, 20 mmol, (Note 9)) in DMF (20 mL) by syringe. A solution of 1-hexylethenyl triflate (10 g, 40 mmol, (Note 5)) in DMF (60 mL) is added at 25°C through the addition funnel over a period of 5 min. The entire mixture is stirred at 25°C for 30 min. The reaction mixture is diluted with ether (200 mL), poured into ice-cooled water (400 mL), and extracted with ether (3 × 200 mL) repeatedly. The combined extracts are washed with aqueous sodium chloride solution (150 mL), dried over anhydrous sodium sulfate, and concentrated with a rotary evaporator (25°C, water bath). The crude product is distilled using a short-path still to give 4.0–4.6 g (82–94%) of 2-hexyl-5-phenyl-1-penten-3-ol, bp 109–111°C at 0.11 mm (Note 10) and (Note 11).
2. Notes
1. This procedure was reported by Stang and Summerville.3
2. 1-Octyne was distilled, bp 125–126°C.
3. Hexane was freshly distilled from sodium or calcium hydride.
4. Trifluoromethanesulfonic acid was distilled, bp 72–73°C at 20 mm.
5. The distilled triflate contained 3–9% of isomers, that were confirmed by capillary GLPC (Silicone OV-17, 50 m, 105°C, 1-hexylethenyl triflate: tR = 11.1 min; isomers: tR = 11.4 and 12.4 min) and 1H NMR analysis. Because the isomers did not interfere with the second reaction, the triflate was employed without further purification. Spectral data of the distilled triflate was as follows: IR (neat) cm−1: 2954, 2930, 2858, 1671, 1419, 1250, 1213, 1141, 943, 899, 703, 610; 1H NMR (CDCl3) δ: 0.89 (t, 3 H, J = 6.9), 1.2–1.4 (m, 6 H), 1.5–1.6 (m, 2 H), 2.34 (t, 2 H, J = 7.5), 4.93 (dt, 1 H, J = 3.5, 1.0), 5.08 (d, 1 H, J = 3.5), 1H NMR peaks of the impurities appeared at δ 2.05–2.20 and 5.18–5.55; 13C NMR (CDCl3) δ: 13.9, 22.4, 25.9, 28.3, 31.3, 33.8, 103.9, 118.5 (q, J = 320, CF3), 157.1.
6. Chromium(II) chloride (95% purity) was purchased from Aldrich Chemical Company, Inc., and used without further purification. The salt is easily oxidized and should be handled under an inert atmosphere.
7. Anhydrous nickel(II) chloride was purchased from Nacalai Tesque Co. and used without further purification. The salt is hygroscopic and should be handled under an inert atmosphere.
8. N,N-Dimethylformamide was refluxed in the presence of calcium sulfate under reduced pressure and distilled with nitrogen bubbling from a capillary, bp 76°C at 39 mm.
9. 3-Phenylpropanal was freshly distilled, bp 97–98°C at 12 mm.
10. The pot residue can be bulb-to-bulb distilled to give an additional 0.5–1 g of product to bring the combined yields to 94–95%. 2-Hexyl-5-phenyl-1-penten-3-ol has the following properties: Rf = 0.29 (ethyl acetate/hexane = 1/10); IR (neat) cm−1: 3340, 3024, 2924, 2854, 1647, 1600, 1497, 1456, 1017, 900, 741, 697; 1H NMR (CDCl3) δ: 0.88 (t, 3 H, J = 6.8), 1.2–1.4 (m, 8 H), 1.7–2.2 (m, 5 H), 2.62 (ddd, 1 H, J = 6.6, 9.6, 13.9), 2.74 (ddd, 1 H, J = 6.1, 9.6, 13.9), 4.10 (dd, 1 H, J = 5.1, 7.5), 4.87 (d, 1 H, J = 1.5), 5.04 (s 1 H), 7.1–7.4 (m, 5 H). 13C NMR (CDCl3) δ: 14.1, 22.6, 27.9, 29.2, 31.4, 31.7, 31.9, 37.0, 74.7, 109.3, 125.7, 128.3, 128.4, 142.0, 152.0.
11. The following ratio of reactants, aldehyde/alkenyl triflate/CrCl2/NiCl2 = 1/2/4/0.02 gave the best results. When the ratio of reagents was reduced to aldehyde/alkenyl triflate/CrCl2/NiCl2 = 1/1/2/0.01, the reaction proceeded slowly. When the reaction was carried out at 25°C for 2 hr, 65% of the 2-hexyl-5-phenyl-1-penten-3-ol was isolated and 14% (GLPC analysis) of the 3-phenylpropanal remained.
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
In the synthesis of a complex molecule, it is sometimes necessary to prepare an organometallic reagent under mild conditions. Because of the strong basicity and nucleophilicity of alkenyllithium and alkenylmagnesium compounds, only a few electrophilic functional groups are stable under the reaction conditions.4 In contrast, the alkenylchromium reagents described here react with aldehydes to give adducts in good to excellent yields in the presence of ketones, esters, amides, acetals, ethers, silyl ethers, and nitriles.5,6,7 The method is especially effective for highly oxygenated molecules.6 Intramolecular cyclization of iodo aldehydes leading to 13-membered lactones has also been reported.8
Addition of a catalytic amount of NiCl2 to CrCl2 is essential for the formation of alkenylchromium reagents.5,6,7 However, a substantial amount of 1,3-diene, the coupling product of the alkenyl iodide, is produced if a higher content of NiCl2 is employed.9,10
Reduction of alkenyl iodides and bromides to alkenylchromium reagents with CrCl2 proceeds smoothly under the same conditions.5,6,7 Several examples of the Grignard-type addition of alkenyl halides and triflates to aldehydes with the combination of CrCl2 and NiCl2 are shown in the Table. Iodoalkenes are more reactive than bromoalkenes (compare run 1 and 2). In the case of an α,β-unsaturated aldehyde, the 1,2-addition product is the main product (run 4). The alkenylchromium reagent adds to an aldehyde group selectively (runs 5–7), as do allyl-11 and alkynylchromium reagents.12 Steric interaction of substituents at a position cis to halogen causes cis-trans isomerization in some cases.10 For example, while the reaction of (E)- and (Z)-2-bromostyrene and benzaldehyde proceeded stereospecifically (runs 8 and 9), both (E)- and (Z)-2-iodo-1-phenyl-1-propene reacted with benzaldehyde to give (E)-1,3-diphenyl-2-methyl-2-propen-1-ol as the sole product (runs 10 and 11). The regiochemistry of double bonds is maintained during the coupling reaction. The CrCl2-NiCl2 system is also effective for the addition of iodobenzene to an aldehyde (run 12).7
TABLE
GRIGNARD-TYPE COUPLING BETWEEN ALKENYL HALIDES (OR TRIFLATES) AND ALDEHYDES, MEDIATED BY THE CrCl2-NiCl2 SYSTEMa

Run

Alkenyl Halide (or Triflate)

Aldehyde

Time hr

Product

Yield %


1

n-C8H17CHO

0.25

100

2

n-C8H17CHO

3

62

3

n-C8H17CHO

3

81

4

(E)-PrCH=CHO

4

64

5

1

87

6

2

78

7

PhCOMe

6

(recovery of PhCOMe, 87%)

8

PhCHO

1

82

9

PhCHO

1

78

10

PhCHO

3

91d

11

PhCHO

3

90d

12

Phl

n-C8H17CHO

3

83


aA mixture of an alkenyl halide (or alkenyl triflate, 2.0 mmol) and an aldehyde (1.0 mmol) was treated at 25°C with CrCl2 (4.0 mmol) and NiCl2 (0.02 mmol) in DMF. bProducts are isolated by column chromatography on silica gel. cThe reaction mixture was heated at 60°C. dThe absence of (Z)-isomer was confirmed by GLPC (Silicone SE-30) and NMR analysis.


References and Notes
  1. Department of Applied Chemistry, Faculty of Engineering, Okayama University, Tsushima, Okayama 700, Japan.
  2. Division of Material Chemistry, Faculty of Engineering, Kyoto University, Yoshida, Kyoto 606–01, Japan.
  3. Stang, P. J.; Summerville, R. H. J. Am. Chem. Soc. 1969, 91, 4600; Summerville, R. H.; Schleyer, P. v. R. J. Am. Chem. Soc. 1974, 96, 1110.
  4. Recently, functionalized alkenyllithiums could be prepared from the corresponding alkenyl iodides by transmetalation in THF:ether:pentane (4:1:1) at −100°C, Tucker, C. E.; Majid, T. N.; Knochel, P. J. Am. Chem. Soc. 1992, 114, 3983.
  5. Takai, K.; Tagashira, M.; Kuroda, T.; Oshima, K.; Utimoto, K.; Nozaki, H. J. Am. Chem. Soc. 1986, 108, 6048.
  6. Jin, H.; Uenishi, J.-i.; Christ, W. J.; Kishi, Y. J. Am. Chem. Soc. 1986, 108, 5644; Aicher, T. D.; Buszek, K. R.; Fang, F. G.; Forsyth, C. J.; Jung, S. H.; Kishi, Y.; Matelich, M. C.; Scola, P. M.; Spero, D. M.; Yoon, S. K. J. Am. Chem. Soc. 1992, 114, 3162.
  7. Takai, K.; Kimura, K.; Kuroda, T.; Hiyama, T.; Nozaki, H. Tetrahedron Lett. 1983, 24, 5281. In 1983 the authors/submitters purchased anhydrous CrCl2 from ROC/RIC Corp. (507-519 Main St., Belleville, NJ 07109) and used it without further purification. The effective lots contained ca. 0.5 mol% of Ni based on Cr.
  8. Schreiber, S. L.; Meyers, H. V. J. Am. Chem. Soc. 1988, 110, 5198.
  9. Kende, A. S.; Liebeskind, L. S.; Braitsch, D. M. Tetrahedron Lett. 1975, 3375; Zembayashi, M.; Tamao, K.; Yoshida, J.-i.; Kumada, M. Tetrahedron Lett. 1977, 4089.
  10. The cis-trans isomerization of the double bond could occur during oxidative addition of triflate to nickel(0), Semmelhack, M. F.; Helquist, P. M.; Gorzynski, J. D. J. Am. Chem. Soc. 1972, 94, 9234.
  11. Hiyama, T.; Okude, Y.; Kimura, K.; Nozaki, H. Bull. Chem. Soc. Jpn. 1982, 55, 561 and references cited therein.
  12. Takai, K.; Kuroda, K.; Nakatsukasa, S.; Oshima, K.; Nozaki, H. Tetrahedron Lett. 1985, 26, 5585.

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

oxygen-free N,N-dimethylformamide

CrCl2-NiCl2

NiCl2

CrCl2

(E)- and (Z)-2-bromostyrene

(E)- and (Z)-2-iodo-1-phenyl-1-propene

n-C8H17CHO

Phl

potassium carbonate (584-08-7)

ethyl acetate (141-78-6)

ether (60-29-7)

sodium bicarbonate,
NaHCO3 (144-55-8)

sodium chloride (7647-14-5)

sodium sulfate (7757-82-6)

nitrogen (7727-37-9)

benzaldehyde,
PhCHO (100-52-7)

calcium sulfate (7778-18-9)

nickel(0) (7440-02-0)

sodium (13966-32-0)

Iodobenzene (591-50-4)

N,N-dimethylformamide,
DMF (68-12-2)

hexane (110-54-3)

chromium(II) chloride (10049-05-5)

argon (7440-37-1)

calcium hydride (7789-78-8)

nickel(II) chloride (7718-54-9)

1-OCTYNE (629-05-0)

triflate

trifluoromethanesulfonic acid (1493-13-6)

3-phenylpropanal (104-53-0)

2-Hexyl-5-phenyl-1-penten-3-ol (187821-45-0)

1-Hexylethenyl triflate (98747-02-5)

(E)-1,3-diphenyl-2-methyl-2-propen-1-ol