Silicon or tin 4-metalated pyrazoles and isoxazoles are synthesized by silyl-or stannylcupration from 4-haloazoles. On the other hand, 5-metalated pyrazoles are prepared by reaction of 5-unsubstituted pyrazoles with LDA and subsequent treatment with chlorosilanes and chlorostannanes. Furthermore, starting from 5-unsubstituted 4-halopyrazoles and applying both methodologies, 4,5-dimetalated pyrazoles bearing silyl groups different from trimethylsilyl or tributylstannyl groups are obtained. Some regioselective ipso-substitutions are also studied.The easy and regioselective ipso-substitution of aryl silanes 1 and stannanes 2 has led to considerable interest in the development of methods which allow the introduction of the silyl and stannyl groups directly into aromatic substrates. We have focused our attention on the synthesis of silylated and stannylated 1,2-azoles because the greatest limitation of our earlier research into isoxazole and pyrazole chemistry was the difficulty in preparing a wide range of functionalized 1,2-azoles. The general procedure for making C-M (M = Si, Sn) bonds (coupling of R 3 MCl with the corresponding Grignard or lithio derivative) has been used for the synthesis of 4-trimethylsilyl-and 4-trimethylstannyl-3,5-dimethylisoxazoles. 3,4 Nevertheless, several attempts to prepare 5-trimethylsilyl-3,4-dimethylisoxazole by treatment of 3,4-dimethylisoxazole with BuLi or MeLi and Me 3 SiCl gave unsatisfactory results 4 because of the very low stability of the intermediate 5-lithioisoxazole. 5 This methodology has also been employed successfully in the synthesis of silyl or stannyl pyrazoles. Thus, Effenberger et al. 6 prepared 4-trimethylsilyl-1-methylpyrazole by silylation of the Grignard derivative from the 4-bromo-1-methylpyrazole and 5-trimethylsilyl-1-methylpyrazole by silylation of the 5-lithio derivative, resulting from lithiation of 1-methylpyrazole with BuLi, with chlorotrimethylsilane in good yields. However, when they started from 4-bromo-1-methylpyrazole and applied both procedures in this order for synthesizing 4,5-bis(trimethylsilyl)-1-methylpyrazole, the yield of the second step was very low (12%). More recently, 7 4-and 5-tributylstannyl-1-phenylpyrazoles were obtained by reaction of 4-and 5-lithio derivatives resulting from lithiation with BuLi of 4-bromo-1-phenylpyrazole and 1-phenylpyrazole, respectively, with tributylstannyl chloride. Other methods, such as 1,3-dipolar cycloadditions 8-10 to metalated alkynes have also been employed in the synthesis of silyl or stannyl pyrazoles and isoxazoles.In this paper we report an interesting alternative to silylation or stannylation of pyrazoles and isoxazoles. We have synthesized, in good yields, silicon and tin 4-metalated pyrazoles or isoxazoles and 5-metalated pyrazoles, as well as 4,5-dimetalated pyrazoles, bearing silyl groups different from the usual trimethylsilyl group. The 4-silyl and 4-stannyl pyrazoles and isoxazoles are obtained from 4-haloazoles by coupling with lithium silyl-or stannylcuprates and the 5-metalated pyrazole...
