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Abnormal Claisen Rearrangement

Published Online: 15 SEP 2010

DOI: 10.1002/9780470638859.conrr001

Comprehensive Organic Name Reactions and Reagents

Comprehensive Organic Name Reactions and Reagents

How to Cite

2010. Abnormal Claisen Rearrangement. Comprehensive Organic Name Reactions and Reagents. 1:1–4.

Publication History

  1. Published Online: 15 SEP 2010

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Abstract

  1. Top of page
  2. General Description of the Reaction
  3. General Reaction Scheme
  4. Proposed Mechanisms
  5. Modification
  6. Applications
  7. Related Reactions
  8. Cited Experimental Examples
  9. References

The first example of abnormal Claisen rearrangement was reported by Lauer and Filbert in 1936. In contrast to the regular Claisen rearrangement (σ migration), the abnormal Claisen rearrangement usually occurs for allyl aromatic ethers. A similar reaction also occurs for the thermal rearrangement of cyclopropyl ketones to homoallylic ketones. The abnormal Claisen rearrangement is believed to proceed via two consecutive processes, i.e., the normal ortho Claisen rearrangement of γ-alkylallyl aryl ether to an o-(α-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, and ZrCl4) have limited ability to accelerate such reaction. 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.

1 General Description of the Reaction

  1. Top of page
  2. General Description of the Reaction
  3. General Reaction Scheme
  4. Proposed Mechanisms
  5. Modification
  6. Applications
  7. Related Reactions
  8. Cited Experimental Examples
  9. References

The first example of abnormal Claisen rearrangements was reported by Lauer and Filbert in 1936. 1 In contrast to the regular Claisen rearrangement ([3,3] σ migration), 2 the abnormal Claisen rearrangement 3 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 γ-alkylallyl aryl ether to an o-(α-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

3 Proposed Mechanisms

  1. Top of page
  2. General Description of the Reaction
  3. General Reaction Scheme
  4. Proposed Mechanisms
  5. Modification
  6. Applications
  7. Related Reactions
  8. Cited Experimental Examples
  9. References

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.

original image

Scheme 1. Concerted mechanism for abnormal Claisen rearrangement.

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Scheme 2. Stepwise mechanism for abnormal Claisen rearrangement.

7 Cited Experimental Examples

  1. Top of page
  2. General Description of the Reaction
  3. General Reaction Scheme
  4. Proposed Mechanisms
  5. Modification
  6. Applications
  7. Related Reactions
  8. Cited Experimental Examples
  9. References
original image

Reference 7.

Caution! The reaction becomes vigorous and exothermic when heated above 200°C, especially on a large scale. To a 25-mL round-bottomed flask 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 flask was gently heated to melt the solid and then placed in a Wood's metal bath at 165–170°C. After an induction period of a few minutes, the liquid in the flask darkened and evolved a gas. When the reaction was finished (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 (65:35:1) as the eluent to give the major normal Claisen rearrangement product and the first 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 (80:20:1) as eluent to give the second abnormal Claisen rearrangement product, i.e., 2,3-dihydroxy-4-allylbenzaldehyde (2) and other minor products.

original image

Reference 3a.

7.1 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 purified by column chromatography on silica gel (hexane-dichloromethane as eluent).

7.2 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 CH2Cl2 was added 200 μL 1.0 M SnCl4 in CH2Cl2 (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 μL 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 purified by silica gel column chromatography using hexane/CH2Cl2 (4:1) as the eluent to give 98% of the rearrangement product as detected by GC.

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

References

  1. Top of page
  2. General Description of the Reaction
  3. General Reaction Scheme
  4. Proposed Mechanisms
  5. Modification
  6. Applications
  7. Related Reactions
  8. Cited Experimental Examples
  9. References