An efficient synthesis of aryl a-keto esters

A new one-pot approach for the synthesis of aryl a-keto ester based on the diazo transfer and oxidation of diazo group is developed. 2005 Elsevier Ltd. All rights reserved. 1 3 Ar OMe O [O] Ar OMe O O Ar OMe N2 [O] Base ArSO2N3 a-Keto acids and esters have been important compounds as natural products and as the building blocks in organic synthesis. Over the past decades, various methods have been reported for the synthesis of such compounds. The most commonly applied synthesis of a-keto ester is the reaction of Grignard reagent to oxalyl chloride, ethyl a-oxo-1H-imidazole-1-acetate or diethyl oxalate. The drawbacks of these approaches are the strict anhydrous reaction condition, the functional group tolerance in the preparation of Grignard reagent, and in some cases the low yield of the reaction. A different but interesting approach is the oxidation of alkynyl derivatives. For example, Wu et al. reported a two-step (bromination and permangnate oxidation) reaction sequence that converts terminal alkynes to a-keto esters. Ruchirauat et al. have recently reported a novel synthesis of aryl a-keto esters based on the rearrangement of aryl cyanohydrin carbonate esters. The approaches through introduction of a keto group to a carbonyl group have also been applied to the synthesis of a-keto acid derivatives. For example, Wasserman et al. developed a method through the formation and singlet oxygen oxidation of enamino carbonyl intermediates. On the other hand, direct oxidation of aryl acetic esters with hydrogen peroxide or molecular oxygen in the presence of transition metal catalyst has recently been reported. Since aryl acetic esters are readily available starting materials, the direct oxidation approach has the advantages over other methods. However, this approach is sometimes limited to a narrow 0040-4039/$ see front matter 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2005.03.199 * Corresponding author. Tel.: +8610 6275 7248; fax: +8610 6275 1708; e-mail: [email protected] range of substrates. For example, in Nolte s system of N-hydroxyphthalimide/Co/O2 the benzylic oxidation works poorly for the arylacetic esters with electron withdrawing substituent in the para position and any substituent in the ortho position. One successful direct oxidation of arylacetic esters has been reported by Choudary et al., in which case the oxidant is tert-butylhydroperoxide (TBHP) and the catalyst is vanadium pillared montmorillonite. Under this condition, wide range of arylacetates with different substituents were smoothly transformed to the corresponding arylglyoxylic esters, with only one exception in which no oxidation occurs when the aryl group was o-nitrophenyl. The drawback of this approach is that the reaction has to be carried out at 70 C for a prolonged time (20–96 h). Here, we report a one-pot conversion of aryl acetic esters to aryl a-keto ester through diazo transfer, followed by oxidation with dimethyldioxirane generated in situ from acetone and Oxone (Scheme 1).