Trimethylsilylacetylene

Rhodium-catalyzed transannulation of 7-halo pyridotriazole with trimethylsilylacetonitrile leads to the generation of imida-zopyridine as depicted in equation eq 34. The mechanism proposed involves generation of a Rh-carbenoid, which upon reaction with TMSCH2CN leads to the corresponding imidazopyridine in 70% yield. 

Related Reagents. r-Butyl Trimethylsilylacetate N,N-T i-methyl-2-(trimethylsilyl)acetamide Ethyl Lithio(trimethylsilyl)-acetate Ethyl 2-(Methyldiphenylsilyl)propanoate Ethyl Trimethylsilylacetate Lithioacetonitrile 

Haruta, R. Ishiguro, M. Furuta, K. Mori, A. Ikeda, N. Yamamoto, H., Chem. Lett. 1982,1093. 

Form Supplied in colorless transparent liquid supplied in ampules. 

Handling, Storage, and Precautions once transferred from the ampule to a sample bottle, it can be stored for long periods without loss of purity and material if stored cold. It is a flammable liquid classified as an irritant. Use in a fume hood. 

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To a solution of ethylnagnesium bromide in 350 ml of THF, prepared from 0.5 mol of ethyl bromide (see Chapter 11, Exp. 6) was added in 10 min at 10°C 0.47 mol of 1-hexyne (Exp. 62) and at 0°C 0.47 mol of trimethylsilylacetylene (Exp. 31) or a solution of 0.60 mol of propyne in 70 ml of THF (cooled below -20°C). With trimethyl si lylacetylene an exothermic reaction started almost immediately, so that efficient cooling in a bath of dry-ice and acetone was necessary in order to keep the temperature between 10 and 15°C. When the exothermic reaction had subsided, the mixture was warmed to 20°C and was kept at that temperature for 1 h. With 1-hexyne the cooling bath was removed directly after the addition and the temperature was allowed to rise to 40-45°C and was maintained at that level for 1 h. 

Monosubstitution of acetylene itself is not easy. Therefore, trimethylsilyl-acetylene (297)[ 202-206] is used as a protected acetylene. The coupling reaction of trimethylsilylacetylene (297) proceeds most efficiently in piperidine as a solvent[207]. After the coupling, the silyl group is removed by treatment with fluoride anion. Hexabromobenzene undergoes complete hexasubstitution with trimethylsilylacetylene to form hexaethynylbenzene (298) after desilylation in total yield of 28% for the six reactions[208,209]. The product was converted into tris(benzocyclobutadieno)benzene (299). Similarly, hexabutadiynylben-zene was prepared[210j. 

Reaction of an acid chloride with trimethylsilylacetylene produces an a,P-ethynyl ketone, which on treatment with substituted hydrazines yields a mixture of 1,5- and 1,3-substituted pyrazoles (34). The ratio is dependent on the reaction conditions (eq. 3). 

It should be noted that a considerable acceleration of the reaction for low-reactive 4-iodopyrazoles is observed for substrates in which acceptor substituents at the pyrazole nitrogen atom additionally play the role of protecting group. Thus, it has been shown (88M253) that iV-phenacyl- and iV-p-tosyl-4-iodopyrazoles interact with phenylacetylene, 2-methyl-3-butyn-2-ol, and trimethylsilylacetylene at room temperature for 3-24 h in 70-95% yields (Scheme 56). 

Norbornadienes, norbornenones and their homologs have been prepared [23, 24] by cycloaddition of cyclopentadiene (21) and cyclohexadiene (22) with l-benzenesulfonyl-2-trimethylsilylacetylene (23) and l-ethoxy-2-carbomethox-yacetylene (24). Both were efficient dienophiles in the cycloaddition processes and dienophile 23 acted as an effective acetylene equivalent (Scheme 2.12). Norbornanes and their homologs can also be attained by Diels-Alder reaction... 

In 2001 the first microwave-enhanced Sonogashira protocol including examples of heteroaromatic skeleta appeared. Trimethylsilylacetylene could be efficiently introduced on electron-rich and electron-deficient heteroaromatics as exemplified by thiophene and pyridine, respectively (Scheme 49) [68]. 

In this approach [92], the glycosyl /3-azides were prepared according to literature procedure [93] and the acetylenes were synthesized in excellent yields via previously reported Pd-catalyzed microwave-assisted Sonogashira crosscoupling protocol with trimethylsilylacetylene, followed by desilylation upon treatment with TEAR... 

In 1980 Sonogashira reported a convenient synthesis of ethynylarenes - the Pd-catalyzed cross-coupfing of bromo- or iodoarenes with trimethylsilylacetylene followed by protiodesilylation in basic solution [15]. Prior to this discovery, formation of terminal acetylenes required manipulation of a preformed, two-carbon side chain via methods that include halogenation/dehydrohalogenation of vinyl- and acetylarenes, dehalogenation of /1,/1-dihaloalkenes, and the Vils-meier procedure [ 14]. With the ready availability of trialkylsilylacetylenes, the two-step Sonogashira sequence has become the cornerstone reaction for the construction of virtually all ethynylated arenes used in PAM and PDM synthesis (vide infra). 

With internal alkynes such as diphenylacetylene and 2-but3me, the perhydroge-nated products were formed in the presence of complex 5 via the corresponding cri-2-alkene as an intermediate (Scheme 5). In case of terminal alkynes such as trimethylsilylacetylene, the desired product was not formed. 

Palladium(O) or readily reduced paUadium(II) complexes were the most efficient catalysts, giving higher yields than analogous Pt catalysts. The Markovnikov product was formed with high regioselectivity. In dialkynes, both C=C bonds could be hy-drophosphorylated, while the C=C double bond in a cyclohexenyl alkyne subshtuent did not react. With trimethylsilylacetylene, unusual anti-Markovnikov selectivity was observed. 

Trimethylsilylacetylene is an exception, giving the anti-Markovnikov product. Internal alkynes also underwent the reaction, as observed without phosphinic acid (Scheme 5-23, Eq. 2). 

The reaction of trimethylsilylacetylene with triallylborane in CDCI3 proceeds stepwise and involves 1,1- and 1,2-allylboration <1968IZV1923, 1999JOM(580)234>. Vinylborane 116 readily cyclizes into compounds 117 and 118 (Scheme 49). 

The series of wide-bite-angle, bulky ligands derived from a cyclobutene scaffold gave Pd complexes (117) showing appreciable activity in the cross-coupling of reactive aryl bromides with trimethylsilylacetylene. A considerable shift of electron density to the phosphorus atoms, probably arising from alternative aromatic canonical structures, may account for the ligand properties.422... 

This reaction is extended to the intramolecular ring closure of the intermediate radical 224 with olefinic or trimethylsilylacetylenic side chains [121]. Cu(BF4)2 is also effective as an oxidant (Scheme 89) [122]. Conjugate addition of Grignard reagents to 2-eyclopenten-l-one followed by cyclopropanation of the resulting silyl enol ethers gives the substituted cyclopropyl silyl ethers, which are oxidized to 4-substituted-2-cyclohexen-l-ones according to the above-mentioned method [123]. (Scheme 88 and 89)... 

Scheme 203 provides a methodology for the conversion of aryl bromides onto 4-aryl-l,2,3-triazoles. In the given example, palladium-copper catalyzed substitution of the bromine atom in indole 1226 by trimethylsilylacetylene provides intermediate 1227. Hydrolysis of the trimethylsilyl protecting group releases terminal alkyne 1228, isolated... 

Trimethylsilylacetylenic ketones are transformed in thioketones with HMDST,73,74 in the presence of TfOTMS, and thioketones trapped with different dienes. 

The coupling of trimethylsilylacetylene with 2,5-diiodo-l,3,4-trimethylpyrrole (121) affords the corresponding bis-acetylene after cleavage of the TMS groups [85]. 

Tischler and Lanza effected coupling of several substituted o-chloro- and o-bromo-nitrobenzenes with trimethylsilylacetylene to give the o-alkynylnitrobenzenes 213 [213], Further manipulation affords the corresponding indoles 214 in good to excellent yield. 

Halopyridines, like simple carbocyclic aryl halides, are viable substrates for Pd-catalyzed crosscoupling reactions with terminal acetylenes in the presence of Pd/Cu catalyst. The Sonogashira reaction of 2,6-dibromopyridine with trimethylsilylacetylene afforded 2,6-bis(trimethylsilyl-ethynyl)pyridine (130), which was subsequently hydrolyzed with dilute alkali to provide an efficient access to 2,6-diethynylpyridine (131) [106]. Extensions of the reactions to 2-chloropyridine, 2-bromopyridine, and 3-bromopyridine were also successful albeit at elevated temperatures [107]. 

Regioselective mono-acetylenation of 2,5-dibromopyridine with trimethylsilylacetylene afforded 2-trimethylsilylethynyl-5-bromopyridine (132) [108, 109]. The regioselectivity was in contrast to the lithiation of 2,5-dibromopyridine in which the 5-position was more reactive. 

Using NaOH as the base, diarylacetylenes have been synthesized from either 2-methyl-3-butyn-2-ol [121] or trimethylsilylacetylene [122], In both cases, NaOH unmasked the protections after the first coupling reaction, revealing the additional terminal alkynyl functionality. Therefore, coupling the adduct 141, derived from 2-iodothiophene and 2-methyl-3-butyn-2-ol, with 2-iodobenzothiophene provided diarylacetylene 142 [121], Analogously, dithienylacetylene (143) was obtained when 2-iodothiophene and trimethylsilylacetylene were subjected to the same conditions [122],... 

Iodobenzothiazole was coupled with trimethylsilylacetylene to give adduct 93 which was readily desilylated to furnish 2-ethynyl-l,3-benzothiazole (94) [52],... 

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