1

Abnormal Claisen Rearrangement

A. GENERAL DESCRIPTION OF THE REACTION The rst example of abnormal Claisen rearrangements was reported by Lauer and Filbert in 1936.1 In contrast to the regular Claisen rearrangement ([3,3] migration),2 the abnormal Claisen rearrangement3 usually occurs for the allyl aromatic ethers. A similar reaction also occurs for the thermal rearrangement of cyclopropyl ketones to homoallylic ketones.4 The abnormal Claisen rearrangement is believed to proceed via two consecutive processes, i.e., the normal ortho Claisen rearrangement of -alkylallyl aryl ether to an o-(-alkylallyl) phenol and the isomerization of the resulting phenol. In general, this type of abnormal Claisen rearrangement does not occur smoothly, except when in the presence of Lewis acids FeCl3 , even though other Lewis acids (e.g., HfCl4 , GaCl3 , ZrCl4 ) have limited ability to accelerate such reaction.3a It is reported that the abnormal Claisen rearrangement can be prevented by the application of 1,1,1,3,3,3-hexamethyldisilazane and N,O-bis(trimethylsilyl)acetamide.5

B. GENERAL REACTION SCHEME

O [3,3] R R R OH OH

Detectable Product

Major Product

Comprehensive Organic Name Reactions and Reagents, by Zerong Wang Copyright 2010 John Wiley & Sons, Inc.

ABNORMAL CLAISEN REARRANGEMENT

C. PROPOSED MECHANISMS Two kinds of mechanisms have been proposed for the abnormal Claisen rearrangement: the concerted process (Scheme 1)6 and the stepwise process consisting of two consecutive steps (Scheme 2).4 However, much experimental evidence is inconsistent with the stepwise mechanism.

SCHEME 1. Concerted mechanism for abnormal Claisen rearrangement.

SCHEME 2. Stepwise mechanism for abnormal Claisen rearrangement.

D. MODIFICATION N/A E. APPLICATIONS This reaction has certain applications in organic synthesis. F. RELATED REACTIONS This reaction is related to the Claisen Rearrangement. G. CITED EXPERIMENTAL EXAMPLES
OH O HO CHO 160170C OH HO + CHO 1 2 HO CHO

Reference 7.

CITED EXPERIMENTAL EXAMPLES

Caution! The reaction becomes vigorous and exothermic when heated above 200 C, especially on a large scale. To a 25-mL round-bottomed ask equipped with a magnetic stirring bar and an air condenser was added 5.06 g 3-hydroxy-2-(2-propenyloxy)benzaldehyde (28.43 mmol). The ask was gently heated to melt the solid and then placed in a Woods metal bath at 165170 C. After an induction period of a few minutes, the liquid in the ask darkened and evolved a gas. When the reaction was nished (detected by TLC) and cooled down, the mixture was triturated 10 times with boiling hexane. The dark, granular residue was dissolved in EtOAc and adsorbed on 10 silica. The mixture was separated by column chromatography using hexane/EtOAc/AcOH ([Link]) as the eluent to give the major normal Claisen rearrangement product and the rst abnormal Claisen rearrangement product, i.e., 2-allyl-3,4-dihydroxybenzaldehyde (1). The hexane extracts were evaporated and chromatographed on silica using hexane/EtOAc/AcOH ([Link]) as eluent to give the second abnormal Claisen rearrangement product, i.e., 2,3-dihydroxy-4-allylbenzaldehyde (2) and other minor products.

O O

H SnCl4 O

Ph

CH2Cl2, 78C

Reference 3a. General Procedure for the Preparation of Geranyl Phenyl Ether To a stirred suspension of 176 mg sodium hydride (60% in oil, 4.4 mmol) in 20 mL THF at room temperature under argon atmosphere was added 0.376 g phenol (4.0 mmol) in portions followed by a catalytic amount of hydroquinone. The mixture was stirred for 0.5 h. HMPA (2 mL) and 0.74 mL geranyl chloride (4.0 mmol) were successively added. The whole mixture was stirred for 1 day. After decomposition of excess sodium hydride with 0.5 mL methanol, the mixture was poured onto ice water and extracted with ether. The combined organic layers were dried, concentrated, and puried by column chromatography on silica gel (hexane-dichloromethane as eluent).

General Procedure for the Enantioselective Cyclization of Geranyl Phenol Ether Promoted by the BINOL-SnCl4 Complex To a solution of BINOL (0.22 mmol) in 4 mL distilled CH2 Cl2 was added 200 L 1.0 M SnCl4 in CH2 Cl2 (0.2 mmol) at 78 C under argon atmosphere. After the mixture was stirred for several minutes at the same temperature, 0.230 g geranyl phenyl ether (0.1 mmol) was added dropwise at 78 C. After the resulting mixture was stirred for 3 days at 78 C, 16 L pyridine (0.2 mmol) was added. Then the mixture was poured onto a saturated NaHCO3 solution and extracted with ether. The combined organic layers were dried over anhydrous MgSO4 and concentrated. The residue was puried by silica gel column chromatography using hexane/CH2 Cl2 (4:1) as the eluent to give 98% of the rearrangement product as detected by GC.

ABNORMAL CLAISEN REARRANGEMENT

Other references related to the abnormal Claisen rearrangement can be found in the literature.8

H. REFERENCES
1. Lauer, W. M. and Filbert, W. F., J. Am. Chem. Soc., 1936, 58, 1388. 2. See Claisen Rearrangement herein (P. 649). 3. (a) Nakamura, S.; Ishihara, K. and Yamamoto, H., J. Am. Chem. Soc., 2000, 122, 8131. (b) Patel, G. N. and Trivedi, K. N., J. Indian Chem. Soc., 1988, 65, 192. (c) Shah, R. R. and Trivedi, K. N., Curr. Sci., 1975, 44, 226. (d) Jain, A. C. and Gupta, R. K., Chem. Lett., 1974, 1353. (e) Mahey, S.; Seshadri, T. R. and Mukerjee, S. K., Indian J. Chem., 1973, 11, 1126. (f) Jain, A. C. and Jain, S. M., Indian J. Chem., 1972, 10, 971. (g) Hansen, H. J., Mech. Mol. Migr., 1971, 3, 177. (h) Jefferson, A. and Scheinmann, F., J. Chem. Soc., C, 1969, 243. (i) Marvell, E. N. and Schatz, B. S., Tetrahedron Lett., 1967, 67. (j) Roberts, R. M. and Landolt, R. G., J. Org. Chem., 1966, 31, 2699. (k) Jefferson, A. and Scheinmann, F., Chem. Commun. (London), 1966, 239. (l) Marvell, E. N.; Anderson, D. R. and Ong, J., J. Org. Chem., 1962, 27, 1109. (m) Habich, A.; Barner, R.; Roberts, R. M. and Schmid, H., Helv. Chim. Acta, 1962, 45, 1943. 4. (a) Roberts, R. M.; Landolt, R. G.; Greene, R. N. and Heyer, E. W. J. Am. Chem. Soc., 1967, 89, 1404. (b) Roberts, R. M. and Landolt, R. G. J. Am. Chem. Soc., 1965, 87, 2281. 5. Fukuyama, T.; Li, G. Q. and Peng, G., Tetrahedron Lett., 1994, 35, 2145. 6. Lauer, W. M.; Doldouras, G. A.; Hileman, R. E. and Liepins, R., J. Org. Chem., 1961, 26, 4785. 7. Kilenyi, S. N.; Mahaux, J. M. and Van Durme, E., J. Org. Chem., 1991, 56, 2591. 8. (a) Puranik, R.; Rao, Y. J. and Krupadanam, G. L. D., Indian J. Chem. Section B: Org. Chem., 2002, 41B, 868. (b) Schobert, R.; Siegfried, S.; Gordon, G.; Mulholland, D.; Nieuwenhuyzen, M., Tetrahedron Lett., 2001, 42, 4561. (c) Ito, H.; Sato, A. and Taguchi, T., Tetrahedron Lett., 1997, 38, 4815. (d) Palani, N. and Balasubramanian, K. K., Tetrahedron Lett., 1993, 34, 5001. (e) Grieco, P. A.; Clark, J. D. and Jagoe, C. T., J. Am. Chem. Soc., 1991, 113, 5488. (f) Shah, R. R. and Trivedi, K. N., Indian J. Chem., Section B: Org. Chem., 1981, 20B, 210. (g) Okely, H. M. and Grundon, M. F., J. Chem. Soc., Perkin Trans. I, 1981, 897. (h) Yagodin, V. G.; Bunina-Krivorukova, L. I. and Balyan, K. V., Zh. Org. Khim., 1970, 6, 2513. (i) Lauer, W. M. and Johnson, T. A., J. Org. Chem., 1963, 28, 2913.