2-Trimethylsilyl-2£/-indazole

Lithiation of 2-alkyl-2/f-indazoles proceeds straightforwardly and thus 3-substituted 2/f-indazoles can be obtained and comparable lithiations of 2-trimethylsilyl-indazoles, followed by removal of the silicon substituent, produce 3-substituted indazoles. 

A route to 3-trimethylsilyl-indazoles involves the interaction of lithium trimethylsilyldiazomethane with benzynes, generated in situ from a halo-benzene. ... 

Trimethylsilyl-indazole konnen durch Trifluormethansulfonsaure-trimethylsilylester oder Zinn(I V)-chlorid-induzierte Glykosylierung indiel-Ribosyl-lH-indazole iibergefuhrt wer-den530. 

When R = H, in all the known examples, the 3-substituted tautomer (129a) predominates, with the possible exception of 3(5)-methylpyrazole (R = Me, R = H) in which the 5-methyl tautomer slightly predominates in HMPT solution at -17 °C (54%) (77JOC659) (Section 4.04.1.3.4). For the general case when R = or a dependence of the form logjRTT = <2 Za.s cTi + b Xa.s (Tr, with a>0,b <0 and a> b, has been proposed for solutions in dipolar aprotic solvents (790MR( 12)587). The equation predicts that the 5-trimethylsilyl tautomer is more stable than the 3-trimethylsilylpyrazole, since experimental work has to be done to understand the influence of the substituents on the equilibrium constant which is solvent dependent (78T2259). There is no problem with indazole since the IH tautomer is always the more stable (83H(20)1713). 

In the case of indazoles the reaction of indazole, 5-nitroindazole or 6-nitroindazole with glycosyl halides and mercury(n) cyanide gives exclusively 2-glycosylindazoles (670), (673) and (675) (7QJHC1435). Similarly, the reaction of 1-trimethylsilyl derivatives of indazole, 3-cyanoindazole, 4-nitroindazole, 5-nitroindazole and 6-nitroindazole with 2,3,5-tri-O-acetyl-D-ribofuranosyl bromide gives only, or preferentially, the 2-ribofuranosyl derivatives (670)-(674) 7QJHC117, 70JHC1329). 

Diazo compounds have also been used as precursors in the preparation of pyrazoles and indazoles. The copper-promoted cycloaddition reaction of lithium acetylides 18 with diazocarbonyl compounds 19 provided a direct and efficient approach to the synthesis of pyrazoles 20 <07AG(I)3242>. A facile, efficient, and general method for the synthesis of 1-arylated indazoles 22 and A-unsubstituted indazoles 23 by the 1,3-dipolar cycloaddition of benzynes, generated from 21, with diazomethane derivatives has been reported <07AG(I)3323>. Reaction of diazo(trimethylsilyl)methylmagnesium bromide with aldehydes or ketones gave 2-diazo-2-(trimethylsilyl)ethanols, which were applied to the synthesis of di- and trisubstituted pyrazoles via [3+2] cycloaddition reaction with ethyl propiolate or dimethyl acetylenedicarboxylate <07S3371>. 

The reaction of diazo(trimethylsilyl)methane (1) with quinones leads mainly to indazoles, the products of a [3 + 2] cycloaddition between the diazo function and a C-C double bond followed by desilylation and oxidation.In contrast, 2-methyl-l,4-naphthoquinone and 2-methoxy-1,4-naphthoquinone require higher reaction temperatures, and no trace of a heterocyclic compound can be detected, rather the trimethylsilyl-substituted cyclopropanes 5 are formed as a mixture of diastereomers. 

A very useful alternative protection of indazoles is achieved using trimethylsilyl chloride in the presence of a hindered base, producing 2-trimethylsilylindazole it is the neutral indazole which is silylated by reaction at the imine nitrogen, the hindered base being present to deprotonate the initially formed salt. ... 

Als Zwischenprodukt bei der Synthese von 1-Glykosyl-lH-indazol (s. S. 840) werder 1-Tri-methylsilyl-lH- bzw. 2-Trimethylsilyl-2H-indazol durch Reaktion von Indazol mit Hexamethylsilazan hergestellt530 60f -f,n7. Der Angriffsort des Silicium-Atoms (N-l oder N-2) wurde nicht bestimmt606,607 bzw. als lH-Isomeres angegeben530. 

Arynes are novel reaction intermediates that react with dienes or 1,3-dipoles to give the corresponding cycloadducts. Recently, many researchers have reported the reaction of benzyne prepared from 2-(trimethylsilyl)phenyl triflate or benzenedia-zonium carboxylate with imines, aminobenzoate, 2-aminobenzophenones, azides, and diazo compounds, which provides various N-containing cycloadducts, such as acridines, acridones, triazoles, and indazoles. Formally, the reaction proceeds in a [2-1-2], [3-1-2], or [4-1-2] manner. Benzyne is an extremely reactive species because of the presence of a strained triple bond and undergoes polar and pericycHc reactions. The lifetime of benzyne in the gas phase has been estimated to around 20 ns (2 X 10" s) by mass spectroscopic techniques. Some spectroscopic properties of benzyne have been determined by Orville Chapman using matrix isolation techniques (Scheme 7.20). 

By employing ortho-(trimethylsilyl)aryl triflates as benzyne precursors, Jin and Yamamoto have reported the synthesis of indazoles under mild reaction conditions by the [3-1-2] cycloaddition of benzyne with diazomethane derivatives, followed by a 1,3-hydrogen shift (Scheme 12.54) [103]. Depending on the stoichiometry of the reagents and the reaction conditions, either 1-arylindazoles 194 or IH-inda-zoles 195 are readily produced in fair to good yields. 

Analogously, 2-diazo-2-(trimethylsilyl)ethanols react with benzynes from o-(trimethylsilyl)aryltriflates to furnish 3-substituted indazoles, [3 + 2] cycloadducts (eq 14). ... 

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