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Org. Synth. 1995, 72, 95
DOI: 10.15227/orgsyn.072.0095
REARRANGEMENT OF trans-STILBENE OXIDE TO DIPHENYLACETALDEHYDE WITH CATALYTIC METHYLALUMINUM BIS(4-BROMO-2,6-DI-tert-BUTYLPHENOXIDE)
[Oxirane, 2,3-diphenyl-, trans- to Benzeneacetaldehyde, α-phenyl-]
Submitted by Takashi Ooi, Keiji Maruoka, and Hisashi Yamamoto1.
Checked by Catherine Gasparski and Larry E. Overman.
1. Procedure

Caution! Trialkylaluminum compounds are pyrophoric and must not be allowed to come into contact with air or moisture. These compounds should only be handled by individuals trained in their proper and safe use.

A. 4-Bromo-2,6-di-tert-butylphenol. A dry, 1-L, three-necked, round-bottomed flask is fitted with a gas inlet, rubber septum, pressure-equalizing dropping funnel, magnetic stirring bar, and a gas outlet tube that is connected to a gas trap containing 0.5 M sodium hydroxide (NaOH). The flask is charged with 103.2 g (500 mmol) of 2,6-di-tert-butylphenol (Note 1) and flushed with argon, after which 200 mL of dry dichloromethane (Note 2) is added. The dropping funnel is charged with 28.2 mL (550 mmol) of bromine and 20 mL of dry dichloromethane. The reaction vessel is immersed in an ice-water bath, stirring is initiated, and bromine in dichloromethane is added over 1 hr. The reaction mixture is stirred at 0°C for 10–20 min (Note 3). Then 60 mL of saturated aqueous sodium sulfite is added slowly at 0°C and stirring is continued at room temperature until the light orange color of bromine is discharged, The mixture is poured into a 1-L separatory funnel containing 400 mL of saturated aqueous sodium bicarbonate (Note 4). The heavier organic layer is separated and the aqueous layer is extracted with two 75-mL portions of dichloromethane. The combined extracts are dried over sodium sulfate and concentrated with a vacuum rotary evaporator. The residue is recrystallized twice from ethanol-water (first with 130 mL of ethanol and 18 mL of water, then with 110 mL of ethanol and 11 mL of water) to furnish 109 g (76% yield) of 4-bromo-2,6-di-tert-butylphenol (Note 5) as light yellow crystals, mp 83–85°C. Pure 4-bromo-2,6-di-tert-butylphenol is reported to melt at 81–82°C.2
B. Diphenylacetaldehyde. A dry, 1-L, three-necked, round-bottomed flask is equipped with a gas inlet, rubber septum, pressure-equalizing dropping funnel, and a magnetic stirring bar. The flask is charged with 3.42 g (12 mmol) of 4-bromo-2,6-di-tert-butylphenol and flushed with argon, after which 600 mL of freshly distilled dichloromethane is added. The mixture is stirred, degassed under vacuum, flushed with argon, and 3 mL (6 mmol) of a 2 M hexane solution of trimethylaluminum (Me3Al, (Note 6)) is injected through the septum to the flask at room temperature. The resulting solution is stirred at this temperature for 1 hr to give methylaluminum bis(4-bromo-2,6-di-tert-butylphenoxide) almost quantitatively (Note 7). The reaction vessel is cooled to a temperature of −20°C in a dry ice/o-xylene bath (Note 8). Then 11.8 g (60 mmol) of trans-stilbene oxide (Note 9) is dissolved in 25 mL of dry dichloromethane, transferred to the dropping funnel, and added over 15–20 min at −20°C. The mixture is stirred at −20°C for 4 hr. After addition of 1.01 g (24 mmol) of sodium fluoride, 324 μL (18 mmol) of water is injected dropwise at −20°C (Note 10). The entire mixture is vigorously stirred at −20°C for 5 min and at 0°C for 30 min. The contents of the flask are filtered with the aid of three 50-mL portions of dichloromethane (Note 11),(Note 12),(Note 13),(Note 14),(Note 15). The combined filtrates are concentrated to ca. 100 mL under reduced pressure with a rotary evaporator. Silica gel (35 g) is added and the remainder of the dichloromethane is removed using a rotary evaporator. The residue is layered on a column of silica gel (500 g, column diameter: 9.5 cm) (Note 12) and eluted (ether/dichloromethane/hexane, 1:2:20 to 1:1:10 as eluants) to give 10.3 g (87%) of diphenylacetaldehyde as a colorless oil (Note 16) and (Note 17).
2. Notes
1. 2,6-Di-tert-butylphenol was obtained from Nacalai Tesque Co. and used without any purification.
2. Solvent grade dichloromethane was dried and stored over Linde type 4 Å molecular sieves.
3. The reaction is conveniently followed by TLC (silica gel, 10:1:1 hexane-CH2Cl2-ether).
4. The extractive workup is performed carefully to avoid vigorous evolution of carbon dioxide gas.
5. The product has the following spectral properties: 1H NMR (200 MHz, CDCl3) δ: 1.39 (s, 18 H, 2 t-Bu), 5.15 (s, 1 H, OH), 7.24 (s, 2 H, Ar-H).
6. Neat trimethylaluminum was obtained from Toso-Akzo Chemical Company Ltd. (Japan) and used as a 2 M hexane solution. The checkers used similar material obtained from Aldrich Chemical Company, Inc.
7. During this operation, nearly 2 equiv of methane gas are evolved per 1 equiv of trimethylaluminum.
8. o-Xylene is recommended as refrigerant in place of carbon tetrachloride.
9. trans-Stilbene oxide was obtained from Aldrich Chemical Company, Inc., and used without any purification.
10. To avoid excessive foaming on hydrolysis water should be added carefully by syringe.
11. The sodium fluoride-water workup offers an excellent method for large-scale preparations, and is generally applicable to product isolation in the reaction of organoaluminum compounds.3
12. The checkers report that GLC analysis (Note 13) at this point shows that the product is contaminated with ca. 4% of trans-stilbene oxide and <1% of the Tischenko product (Note 14).
13. Gas chromatography conditions are as follows: Supelco fused silica capillary SPB-1 column (30 m, 0.32-mm ID, 0.25 micrometers df), 100°C initial temperature, 280°C final temperature, 10°C/min. The following retention times were obtained: diphenylacetaldehyde (6.7 min), trans-stilbene oxide (7.4 min), Tischenko product (18.2 min).
14. The Tischenko product, Ph2CHCO2CH2CHPh2, has the following properties: mp, 95–98°C, 1H NMR (300 MHz, CDCl3) δ: 4.35 (t, 1 H, J = 7.5), 4.70 (d, 2 H, J = 7.5), 4.92 (s, 1 H), 7.11–7.40 (m, 20 H); 13C NMR (75 MHz, CDCl3) δ: 49.7, 57.2, 67.4, 126.8, 127.1, 128.2, 128.47, 128.53, 138.3, 140.8, 172.2; HRMS (CI, isobutane) Calcd for C28H24O2: 393.1854 (MH); Found: 393.1829; IR (CCl4) cm−1: 3094–2906, 1737, 1600, 1494, 1450, 1144.
15. Merck Kieselgel 60 (Art. 9385) was used. The checkers found that loading the column in this way avoids precipitation of a by-product during column elution. The chromatography removes a few percent of remaining epoxide and 4-bromo-2,6-di-tert-butylphenol.
16. The product is >99% pure by capillary GLC analysis (Note 13) and has the following spectral characteristics: 1H NMR (200 MHz, CDCl3) δ: 4.92 (d, 1 H, J = 2.6, CH), 7.20–7.49 (m, 10 H, 2 Ph), 9.98 (d, 1 H, J = 2.6, CHO).
17. The rearrangement is considerably faster when the reaction solution is more concentrated. If 480 mL of dichloromethane is used, the rearrangement is complete within 20 min at −20°C. However, the checkers found that the crude product is contaminated with 3–10% of the Tischenko product (Note 14), which is difficult to remove by chromatography. This by-product can be removed by vacuum distillation (bp 136–144°C, 2 mm). Using this combined purification procedure, the checkers obtained 9.6 g (81%) of diphenylacetaldehyde of >99% purity by capillary GLC analysis (Note 13).
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
This catalytic procedure illustrates a general method for preparing a wide range of carbonyl compounds by the selective rearrangement of epoxides under the influence of the exceptionally bulky, oxygenophilic methylaluminum bis(4-bromo-2,6-di-tert-butylphenoxide) (MABR) as catalyst.4 The advantages of catalytic versions include economy, ease of large-scale preparation and isolation, and the synthetic potential for in situ derivatization of the carbonyl products. Use of a sodium fluoride-water (NaF-H2O) workup3 further simplifies the experimental operation. As revealed in Tables I and II, the amount of the catalyst varies from 5 to 20 mol% depending on the epoxy substrates. Yields when MABR is used stoichiometrically are also included for comparison. Certain epoxy substrates require stoichiometric MABR. Neither epoxides derived from monsubstituted olefins nor from certain internal dialkyl-substituted olefins can be rearranged by MABR, however, even using two equivalents.
TABLE I
MABR-CATALYZED REARRANGEMENT OF EPOXIDES

Epoxide

MABR (mol %)

Product

Yield (%)


200

93

10

95

200

98

10

96

5

91

200

87

10

90

5

84

200

94

20

58

200

96

20

0

200

73

20

0


TABLE II
MABR-CATALYZED REARRANGEMENT OF CHIRAL EPOXY SILYL ETHERS

Epoxy Silyl Ether

MABR (mol %)

β-Siloxy Aldehyde

Yield (%)


200

99

20

82

10

74

200

98

20

79

10

68

200

87

20

74

10

71

200

88

20

77


The MABR-promoted rearrangement, when applied to optically active epoxy substrates, has been shown to proceed with rigorous transfer of the epoxide chirality. Accordingly, used in combination with the Sharpless asymmetric epoxidation of allylic alcohols,5 this rearrangement represents a new approach to the synthesis of various optically active β-siloxy aldehydes, useful intermediates in natural product synthesis (Table II).4,6
The stronger coordination of a carbonyl oxygen than an epoxide oxygen to an aluminum reagent requires the stoichiometric use of MABR at low temperature. The key element of the present modification is the use of a higher reaction temperature (though still at or below 0°C) than the previously reported conditions7 in order to induce dissociation of the aluminum reagent-carbonyl complex, thereby allowing regeneration of MABR as catalyst for further use in the catalytic cycle of the reaction. The facile dissociation of the organoaluminum-carbonyl complex as well as the smooth rearrangement of epoxides is apparently ascribable to the exceptional bulkiness of MABR compared to other ordinary Lewis acids.8 The less bulky methylaluminum bis(4-bromo-2,6-diisopropylphenoxide) was found to be totally ineffective for the rearrangement of the tert-butyldimethylsilyl ether of epoxy geraniol.

References and Notes
  1. Department of Applied Chemistry, Faculty of Engineering, Nagoya University, Chikusa, Nagoya 464–01, Japan.
  2. Ley, K.; Muller, E.; Mayer, R.; Scheffler, K. Chem. Ber. 1958, 91, 2670.
  3. Yamamoto, H.; Maruoka, K. J. Am. Chem. Soc. 1981, 103, 4186.
  4. Maruoka, K.; Nagahara, S.; Ooi, T.; Yamamoto, H. Tetrahedron Lett. 1989, 30, 5607; Maruoka, K.; Ooi, T.; Nagahara, S.; Yamamoto, H. Tetrahedron 1991, 47, 6983.
  5. Hill, J. G.; Sharpless, K. B.; Exon, C. M.; Regenye, R. Org. Synth., Coll. Vol. VII 1990, 461; Gao, Y.; Hanson, R. M.; Klunder, J. M.; Ko, S. Y.; Masamune, H.; Sharpless, K. B. J. Am. Chem. Soc. 1987, 109, 5765.
  6. Maruoka, K.; Sato, J.; Yamamoto, H. J. Am. Chem. Soc. 1991, 113, 5449.
  7. Maruoka, K.; Ooi, T.; Yamamoto, H. J. Am. Chem. Soc. 1989, 111, 6431.
  8. Parker, R. E.; Isaacs, N. S. Chem. Rev. 1959, 59, 737; Rickborn, B.; Gerkin, R. M. J. Am. Chem. Soc. 1971, 93, 1693; Milstein, D.; Buchman, O.; Blum, J. Tetrahedron Lett. 1974, 2257; Rao, A. S.; Paknikar, S. K.; Kirtane, J. G. Tetrahedron 1983, 39, 2323.

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

methylaluminum bis(4-bromo-2,6-di-tert-butylphenoxide) (MABR)

Dry Ice

ethanol (64-17-5)

ether (60-29-7)

sodium sulfite (7757-83-7)

sodium hydroxide (1310-73-2)

sodium bicarbonate (144-55-8)

bromine (7726-95-6)

sodium sulfate (7757-82-6)

oxygen (7782-44-7)

carbon tetrachloride (56-23-5)

carbon dioxide (124-38-9)

methane (7782-42-5)

dichloromethane (75-09-2)

sodium fluoride (7681-49-4)

hexane (110-54-3)

argon (7440-37-1)

Diphenylacetaldehyde,
Benzeneacetaldehyde, α-phenyl- (947-91-1)

trimethylaluminum (75-24-1)

trans-Stilbene oxide,
Oxirane, 2,3-diphenyl-, trans- (1439-07-2)

Methylaluminum bis(4-bromo-2,6-di-tert-butylphenoxide) (118495-99-1)

4-Bromo-2,6-di-tert-butylphenol (1139-52-2)

2,6-di-tert-butylphenol (128-39-2)

o-Xylene (95-47-6)

Methylaluminum bis(4-bromo-2,6-diisopropylphenoxide)

tert-butyldimethylsilyl ether

epoxy geraniol