Trimethylsilylacetylene, reaction with

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]. 

The reaction chemistry of germyne 172 has been investigated. Reaction with diphenylacetylene produces the digermacyclobutadiene 179 (Equation (326)), while treatment with excess trimethylsilylacetylene affords the bicyclic compound 180 (Scheme 69), which results from the formation of a biradical intermediate.394... 

The synthesis of cyclic tetraselenadiynes could be achieved by a stepwise approach. Key steps were the reaction of the lithium salt of trimethylsilylacetylene 168 with a,ra-diselenocyanatoalkanes 169. By treating the bis-lithium salt of the resulting a,u -diselenaalkadiynes 170 again with 169, the cyclic tetraselenadiynes 172 resulted with methylene chains between the Se-C=C-Se units (Scheme 19) <2002JOC4290>. 

A catalytic amount of CuCl was found to activate alkynyl(trimethyl)silanes in the palladium-catalyzed coupling reaction with aryl triflates (Eq. 7) [12]. The catalytic cycle is considered to involve the transfer of an alkynyl group from an alkynylsilane to Cu(I) and then to palladium(II). A sequential palladium-catalyzed reaction of trimethylsilylacetylene gives unsymmetrical diarylacet-ylenes (Eq. 8). 

The reaction of ate complexes (24), formed from trialkylboranes and trimethyl-silylpropargyl phenyl ether, with a mixture of acetic acid and hexamethylphosphoric triamide (HMPT) gives trimethylsilylacetylenes (25) selectively (Eq. 54) whereas the corresponding trimethylsilylallenes (26) are selectively prepared by the reaction with sodium methoxide instead of acetic acid and HMPT (Eq. 54) In the latter, when primary alkylboranes are used, the corresponding allene derivatives are obtain in high purity, but secondary alkylboranes give reverse ratios of the isomer distribution. 

Trimethylsilylacetylene gave in reaction with AII3B a complicated mixture of products [eq. (3)]. Only compound 1 is produced by 1,1-organoboration. 1,2-Addition of... 

Glycals serve as activated sugars because of the inherent reactivity of the endocyclic enol ether. Consequently, they have been extremely useful substrates in their complementarity to native activated sugars. Additionally, they have been used to demonstrate versatility not directly available from other sugar derivatives. In a good example of the utility of allylsilanes and silylacetylenes in C-glycoside chemistry, Ichikawa et al. [91] demonstrated a preference for the a anomer in all cases. The results, shown in Scheme 7.17, included a demonstration that a characteristic nOe can be used to confirm the stereochemical outcome of the reaction with hw-trimethylsilylacetylene. 

As simple glycals are substrates for C-glycosidations, so are 1-substituted glycals. An example of C-glycosidations on substituted glycals was reported by Nicolau, etal.,7 and is illustrated in Scheme 2.3.40. In this study, reactions with allyltrimethylsilane and methyl trimethylsilylacetylene were explored. Utilizing titanium tetrachloride as the catalyst, yields in excess of 75% were obtained and the products exhibited the stereochemistry shown. 

Scheme 15.49. Palladium-catalyzed Sonogashira reaction with trimethylsilylacetylene.

In contrast, palladium(0)-catalyzed coupling of the requisite starting oxazole for the synthesis of hippadine 219 with trimethylsilylacetylene at 80°C did not afford the expected oxazole-alkyne 220 (Fig. 3.64). Instead, they isolated the tricyclic furan 221 derived from a Diels-Alder retro-Diels-Alder reaction in 77% yield. Thermolysis of 221 at 320°C effected an intramolecular Diels-Alder reaction with concomitant desUylation. Subsequent DDQ oxidation of this product (not shown) then provided hippadine. 

Copper Reactants. Application of the Pd/Cu-catalyzed cross-coupling, the Sonogashira reaction, with monosubstituted or protected acetylene gives rise to a variety of ethynyl-heteroarenes (Schenae 27). Reactions with trimethylsilylacetylene or phenylacetylene in... 

A similar approach was used by Knochel and coworkers for the first synthesis of unsubstituted b-SFs-indole (7) (12CEJ10234). They directly used unprotected 2-bromo-5-SF5-aniline (8) in reaction with trimethylsilylacetylene under Sonogashira cross-coupling conditions, which provided SFs-substituted 2-ethynyl(trimethylsilyl)aniline (9). Subsequent cychzation using KH in 1-methyl-2-pyrrolidinone afforded the b-SFs-indole (7) in 83% yield (Scheme 3). 

This methodology was also applied in the first enantioselective syntheses of (+)-dictyopterene A and C, isolated from Hawaian seaweed belonging to genus Dictyopteris and presenting physiological activities (Scheme 2). The key intermediate, allylic benzoate 7, was prepared in a few steps starting from trimethylsilylacetylene 6, with 85% enantiomeric excess. The Pd-catalyzed reaction of 7 in the presence of a catalytic amount of Pd(dppe)2 and sodium hydride as base led cleanly to cyclopropane 8, which was desul-fonylated, reduced, and oxidized to give a mixture of cis- and trans- (60 40) aldehydes. 

Reaction of Trimethylsilylacetylene/Acetylide with Electrophiles. Deprotonation of TMSA with n-BuLi or Grignard reagents produces nucleophilic acetylides, which can react with various electrophilic carbon centers such as carbonyls, alkyl halides, or epoxides. 

Reaction with Diazomethane to Form Silylated Cyclopropanes and Cyclohutanones. The reaction of (1) and diazomethane results in a mixture of products. Treatment of equimolar amounts of (1) with diazomethane at — 130°C leads to (trimethylsilyl)cyclopropanone in moderate yield (eq 12). The product obtained can then react with a second equivalent of diazomethane upon warming to — 78°C, resulting in ring expansion to a mixture of 2- and 3-(trimethylsilyl)cyclobutanones. Alternatively, these isomeric products may be obtained directly with 2 equiv of diazomethane. Treatment of the isomeric (trimethylsilyl)cyclobutanone mixture with methanol makes it possible to obtain pure 3-substituted isomer in 84% yield. This 3-(trimethylsilyl)cyclobutanone derivative can also be formed by a more elaborate route via the regioselective [2 + 2] addition of dichloroketene to trimethylsilylacetylene followed by hydrogenation and reductive removal of the two chlorine atoms. trimethylsilyidiazomethane has also been reported to react with (1) to form bis-silyl substituted cyclopropanones. ... 

The monoiodo derivative 74 was then converted to the ethynyl substituted phthalocyanine 76 by reaction with trimethylsilylacetylene ([Pd(PPh3)2Cl2], Cul, EtjN, THF, RT, 24 h) followed by desyUlation of 75 (TBAF, THF, 0 C-rt, 2 h, 65 %). Then 1,3-butadiyn bridged dimer 77 was obtained by copper catalysed Glaser homo-coupling reaction (CuCl, pyridine, rt, 3 days, 75 %) [62],... 

However, in this case the electron-rich 1-methoxypropyne was used as the monoalkyne. First, 108 was converted into yne-ynamide 109 by three steps, including a Sonogashira reaction with trimethylsilylacetylene and the ynamide formation based on the alkynyliodonium salt 105. Yne-ynamide 109 was then alkylated with iodopen-tane, and subsequent desilylation with TBAF provided the diyne 110 (44% yield over two steps). The key cyclotrimerization of diyne 110 with 1-methoxypropyne was carried out in toluene at room temperature in the presence of 10 mol % of Wilkinson s catalyst and afforded chemo- and regioselectively carbazole 111 (82% yield, isomer... 

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). 

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