Synthesis of ortho-Substituted Arylacetic Esters and Related Compounds by Means of Sommelet-Hauser Rearrangement of Sulfur Ylides

Abstract

The rearrangement of a series of dimethylsulfonium α-substituted benzylides, e.g., 8, in ethanol has been examined. The ylides 8a, b generated in situ by treatment of the sulfonium salts 7a, b with 1, 8-diazabicyclo[5.4.0]undec-7-ene (DBU) in ethanol at room temperature, afforded the o-(methylthiomethyl)phenylacetic esters 10a, b as a result of the Sommelet-Hauser rearrangement of the tautomeric ylides 9a, b. By contrast, the ylide 14 possessing a furan ring was stable at room temperature, but, on heating in ethanol, gave the rearranged product 15. The ylide 22 stabilized by an acetyl group provided three rearranged products, 23, 24, and 25, in boiling ethanol. Treatment of the sulfonium salts 30a, b with DBU at room temperature afforded the corresponding rearranged products 31a, b. The sulfonium salt 34a prepared from 33a, on treatment with sodium ethoxide, gave the rearranged product 36a, which was then S-methylated and treated with DBU to give the 1, 2, 3-trisubstituted benzene 37a. This method was applied to the synthesis of the fenoprofen analog 39 from 39 from 33b, c.