A comparative study on the photo-induced arylation of β-dicarbonyl compounds by arylazosulfides and its use in the synthesis of methyl labeled 2-arylpropionic acids

Abstract A comparative study on the arylation of β-dicarbonyl derivatives (acetylacetone, methyl acetoacetate and dimethyl malonate) by using the photo-induced decomposition of arylazosulfides is presented. The arylazosulfides used contained the aryl moieties related to Ketoprofen or Ibuprofen and the reaction was performed following the procedure reported by Dell'Erba et al. ( Tetrahedron , 1991 , 47 , 333). From the arylazosulfides assayed, only those bearing a carbonyl group attached to the benzene ring, i.e., 1 and 11 , afforded the corresponding arylation adducts in satisfactory yields. Concerning the β-dicarbonyl derivatives, condensation of acetylacetone in the case of 1 and of dimethyl malonate in that of 11 gave the best results. However, the further methylation of the aryl β-dicarbonyl adduct was clearly advantageous for the case of the 2-arylmalonate derivatives. The use of this synthetic strategy for the convenient preparation of Ketoprofen (23% overall yield, 7 steps from 3-nitrobenzophenone) and Ibuprofen (34% overall yield, 8 steps from 4-isobutyrylbenzene) isotopomers labeled at the methyl group at C-2 is also reported.