Silylations heteroaromatic compounds

Yttrium-catalyzed cyclization/hydrosilylation was also applied to the synthesis of silylated heteroaromatic bicyclic compounds. Reaction of l-allyl-2-vinyl pyrrole (32, n = R = H) with phenylsilane catalyzed by [(Gp )2YMe]2 at room temperature for 6 h followed by oxidation gave the corresponding heterobicycle amine 33 in 90% yield as a 98 2 mixture of isomers (Equation (23)). It was noteworthy that selective conversion of 32 to 33 required initial... 

Table 1. Silylations of C-H bonds in aromatic and heteroaromatic compounds and of benzyl C-H bonds 6mol%...

Vinylsilanes can function as a silylating reagents for C-H bonds in heteroaromatic compounds (Scheme 5) [12]. The reaction of furan 7 with vinylsilane 8 using Ru3(CO)12 as a catalyst affords the /1-silylation product in 98 % yield. This silylation can be applied only to heteroaromatic esters, ketones, and amides. For this reaction, RuHCl(CO)(PPh3)3 also has catalytic activity. 

N-Acyliminium ion pools react with various carbon nucleophiles as summarized in Scheme 5.16. For example, allylsilanes, silyl enol ethers, Grignard reagents, and 1,3-dicarbonyl compounds serve as good nucleophiles. Aromatic and heteroaromatic compounds also react as nucleophiles with N-acyliminium ion pools to give Friedel-Crafts-type alkylation products.N-Acyliminium ions are known to serve as electron-deficient 4n components and undergo [4 -F 2] cycloaddition with alkenes and alkynes. Usually these reactions take place very quickly, and therefore N-acyliminium ion pools serve as effective reagents for flash chemistry. 

The sUylation of aromatic or heteroaromatic compounds can be performed via magnesiated or lithiated intermediates, which can be accessed by hydrogen-metal or halogen-metal atom exchange. Thus, C-4 silylation of imidazoles is achieved from4-iodo imidazoles (eq 45), while C-2 silylated oxazoles are prepared by addition of TMSOTf to the lithiated oxazole (eq 46) interestingly, for this reaction, the employment of TMSCl as electrophile... 

Heteroaromatic compounds are also suitable nucleophiles in the Michael additions to enals catalysed by prolinol silyl ethers. Hayashi and coworkers demonstrated that oxazolinones can add effectively to enals (Scheme S.lSa)." Indole also added effectively to a,p-unsaturated aldehydes (Scheme 8.13b). Also, enantioselective Michael addition of simple 3(2H)-furanones to a,(3-unsaturated aldehydes has been described (Scheme 8.13c). ... 

Summary Pure and mixed substituted indoyl-, pyrroyl-, and furanyl-silanes are formed in the reaction of heteroaromatic compounds with lithium alkyls and halosilanes (1-3). Chains of silyl-bridged molecules are available (7). The crystal structure of a lithium derivative (10) is presented and the 1,2-silyl group migration from nitrogen to carbon is proved. Formation of a 16-membered macrocycle (12) containing four indole molecules is described. 

A few sihcon-containing linkers have been synthesized on sohd phase and are used to tether diverse aryl moieties without former preloading of the linker. Elhnan et aL attached aromatic and heteroaromatic compounds directly to a sihcon-substituted support for the first time. The nature of the resin anchoring of those silyl hnkers has to be chosen carefully because cleaving conditions for the release of non-alcohohc compounds may induce destruction (and therefore release) of the sihcon hnker as well. Ellman et al. synthesized a heteroatom free, masked and therefore stable silyl hnker 650 starting from allylsilanes and bromo-substituted polystyrene that can be eas-... 

A wide range of nucleophilic substrates of different reactivity were trifluoromethylated with these reagents. The substrates include carbanions, activated aromatics, heteroaromatics, enol silyl ethers, enamines, phosphines, thiolate ions and iodide anions. " (Scheme 3.8) The least reactive substrates, such as triphenylphosphine, aniline and phenols, require the use of the most reactive dinitro derivative. Most of the reactions can be conveniently performed with the unsubstituted 5-trifluoromethyl dibenzothiophenium salt (35). The least reactive sulfonium salts are the acyclic sulfonium compounds which reacted only with the sodium thiolates.55,59... 

Only a few papers on silyl derivatives of heteroaromatics, e.g. indoles and pyrroles, have been published [1-7], After the synthesis of mono-, bis-, tris-, and tetralds(indol-l-yl)silanes and (pyrrol-l-yl)silanes, this chemistry is extended to furan compounds [7, 8]. A further interest is to couple the heterocycles with bridging silyl groups to obtain chains and cyclic molecules. 

Direct Silylation of Heteroarylcarbonyl Compounds. Under ruthenium catalysis vinyltrimethylsilane reacts to ortho silyl-ate heteroaryl carbonyl compounds directly in good yields (eqs 32 and 33). The reaction only works with heteroaromatic systems. The resulting aryltrimethylsilanes can be used to introduce electrophiles regioselectively through electrophilic desilyla-tion. The reaction also works with vinyltriethoxysilane, opening the possibility of silicon-based cross-coupling reactions. 

Shortly after Sadighi and Buchwald s 2003 report, Nolan reported that [(IPr)CuCl] could be used in the hydrosilylation of simple ketones, leading to the silylated alcohols in high yields. Subsequent work permitted the development of fine-tuned catalytic systems for different classes of carbonyl compounds. Hence, while [(IPr)CuCl] was found optimal for the 1,4-reduction of conjugated carbonyls and 1,2-reduction of simple ketones, [(ICy)CuCl] proved more efficient for hindered carbonyl substrates and [(SIMes)CuCl] turned out to be the best choice for heteroaromatic ketones (Scheme 11.1). Other NHC architectures e.g. six-membered diamino carbenes) and alternative... 

Trimethylsilyl [ C]cyanide is conveniently accessible from trimethylsilyl chloride, Na CN and Nal in the presence of lutidine or pyridine ". In carbon-14 synthesis it is normally generated in situ and used immediately in subsequent Lewis acid catalyzed chemical transformations. It is useful for some reactions in which alkah metal [ " C]cyanides normally fail, such as cyanide addition to acetals and aromatic and heteroaromatic aldehydes and ketones. Examples include the Znl2-catalyzed addition of TMS " CN to 2-furaldehyde followed by hydride reduction of the resultant silylated cyanohydrin to the aminoalcohol 96 " and the SnCLj-catalyzed formation of D-[l- " C]allonitrile 98, obtained from reaction of TMS " CN to the 0-acetylated hemiacetal 97 (Figure 7.26). Subsequent addition of H2Se to the nitrile group, cyclocondensation of the intermediate selenoamide in situ with ethyl bromopymvate and deprotection yielded 99, precursor to [2- " C]CI-935, a compound with... 

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