Rearrangements of Cycloalkenyl Aryl Ethers

Abstract

Rearrangement reactions of cycloalkenyl phenol and naphthyl ethers and the acid-catalyzed cyclization of the resulting product were investigated. Claisen rearrangement afforded 2-substituted phenol and naphthol derivatives. Combined Claisen and Cope rearrangement resulted in the formation of 4-substituted phenol and naphthol derivatives. In the case of cycloocthylphenyl ether the consecutive Claisen and Cope rearrangements were followed by an alkyl migration. The mechanism of this novel rearrangement reaction is also discussed.

Keywords: Claisen rearrangement; Cope rearrangement; naphthyl ethers; phenol ethers; reaction mechanism.

Scheme 1

Acid-catalyzed rearrangement of ethers 3.

Scheme 2

Ring-contraction rearrangement of compound 6c.

Figure 1

Free energy profiles for the Cope rearrangement reactions of compounds 4a, 4b and 4c. The letters designate the reaction intermediate and transition states as displayed in Figure 2. The final deprotonation step is indicated by the last dashed lines. Color code: dark grey line—4a; blue—4b; red—4c.

Figure 2

The mechanism of the proton-catalyzed Cope rearrangement. (A): the most stable protonated form; (B): suitable tautomeric form for Cope rearrangement; (C): first transition state (TS₁); (D): intermediate structure; (E): second transition state (TS₂); (F): protonated product state. Color code: green—carbon; red—oxygen; white—hydrogen.

Figure 3

Calculated PES (in kcal/mol) for compound 4a as a function of the breaking (horizontal axis) and forming CC bonds (vertical axis). The zero level is set to the most stable structure within the calculation domain. The most stable reactant and product regions are only partially shown at the upper left and lower right corners. TS and intermediate regions are indicated by white circles.

Scheme 3

Rearrangement of quinoline 12.