Concise Synthesis of Licochalcone A through Water-Accelerated [3,3]-Sigmatropic Rearrangement of an Aryl Prenyl Ether

Abstract

Claisen-Schmidt condensation of 4-(tetrahydropyran-2-yloxy)acetophenone with 2-methoxy-4-[(3-methylbut-2-en-1-yl)oxy]benzaldehyde gave a THP-protected chalcone ether. Removal of the THP group under mild acidic conditions gave the corresponding chalcone ether, which underwent a water-accelerated Claisen rearrangement under microwave irradiation or heating in a sealed tube in aqueous ethanol to give a good yield of licochalcone A, which has diverse biological activities; no product of deprenylation or abnormal Claisen rearrangement was formed. The abnormal Claisen rearrangement of γ-substituted allyl aryl ethers is known to be a problem in [3,3]-sigmatropic rearrangement reaction; this, however, was not detected in our water-accelerated system.

rearrangements - condensation - natural products - licochalcone A

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This compound has been reported to be an oily liquid (see ref. 12a), but we obtained it as a white solid.