Coupling trimethylsilylacetylene

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. 

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... 

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. 

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],... 

Initially, 31 was obtained as the Sonogashira adduct of 2-chloro-3,6-diisobutylpyrazine and trimethylsilylacetylene. Interestingly, 31 underwent an additional Sonogashira coupling with 2-chloropyrazine (13) to afford unsymmetrical 1,2-bispyrazinylacetylene 32 in excellent yield [26], Here, desilylation occurred in situ, and the resulting terminal alkyne was then coupled with 13. 

Coupling of excess (Z)-l,2-dichloroethene (217) with propargyl alcohol first led to the enyne 218, which, when subjected to a second Pd-catalyzed coupling step with trimethylsilylacetylene, provided the mixed diacetylene 219. With all carbon atoms assembled, the allene function was generated by first producing the (unprotected) hydrazine derivative 220, which on treatment with either diethyl azodicarboxylate (DEAD) or 4-methyl-l,2,4-triazoline-3,5-dione (MTAD) under anaerobic conditions at 0 °C yielded the hydrocarbon 27. According to mechanistic studies, the latter process leads first to a mixture of ( )- and (Z)-diazenes. Sigmatropic elimination of... 

Although the Sonogashira reaction is normally performed with a copper cocatalyst, a copper-free, one-pot procedure for direct coupling with l-aryl-2-trimethylsilylacetylenes has been developed <2005T2697>. The procedure uses a mixture of palladium acetate and tri(o-tolyl)phosphine as catalyst in the presence of tetra- -butylammonium chloride... 

Coupling of/r-Bromonitrobenzene with Trimethylsilylacetylene in the Presence of Catalytic Amounts of PdfPPhj) and CuJ... 

The palladium catalysed coupling of trimethylsilylacetylene and the iodopyridone derivative shown in 3.57. led to the formation of the corresponding ethynylpyridine. The absence of the spontaneous ring closure to furo 2,3-/)]pyndinc might be attributed to the preference of the pyridone form over the hydroxypyridine form. Addition of a copper catalyst and base, however, led to the closure of the fiiian ring (3.57.),73 The same approach was utilised in the functionalization of uracil based nucleosides.74... 

Besides serving as a platform for the construction of the pyrrole ring (see Chapter 3.), the Sonogashira coupling is also effective in functionalising the same system. Trimethylsilylacetylene was used as a surrogate to introduce acetylene groups into the 2 and 5-positions of pyrrole (6.43.), 2,5-diiodo-... 

The Sonogashira coupling of halopyridines was also achieved by other means. Resin bound bromopyridine derivatives, for example, underwent smooth coupling with acetylenes as well as with arylboronic acids and aryltin reagents.44 The advantageous effect of microwave irradiation on the coupling of halopyridines and trimethylsilylacetylene was also reported.45... 

Although the Sonogashira-coupling of heterocycles is usually limited to their bromo and iodo derivatives, in certain cases the cross-coupling might also be achieved on activated chloro compounds. The chloro derivative shown in 8.23. was coupled with trimethylsilylacetylene.32 In another example the imidoyl chloride subunit of the 5-chloro-1,4-benzodiazepine derivative shown in 8.27. coupled efficiently with phenylacetylene to give the expected disubstituted acetylene derivative.15... 

Figure 4.7. Infrared spectra used to monitor cross-coupling and deprotection reactions on resin-bound phenylacetylene oligomers. Observation of a null at 3311 and 2156 cm-1 corresponds to complete acetylene coupling and trimethylsilylacetylene deprotection, respectively.

Oxidative coupling of terminal acetylenes in the presence of copper(I) catalysts is the best method of preparing symmetrically substituted butadiyne derivatives,5 and has been applied to the coupling of trimethylsilyl-acetylene. Better yields are obtained using the Hay procedure in which the catalyst is the TMEDA complex of copper(I) chloride.7 The procedure submitted here is an improved version of Walton and Waugh s synthesis of BTMSBD by the Hay coupling of trimethylsilylacetylene.2 BTMSBD has also been prepared by... 

The reaction of 5-iodothiophene-2-carbaldehyde with 2-propynylthio-phene gave a mixture of products (94JCS(P1)1245). Also, the reaction of t lenyl-trimethylsilylacetylene with 5-iodothiophene-2-carbaldehyde did not give any interesting result. In fact, with the expected coupling product 169, the authors obtained a product deriving from the desilylation reaction 170 and from the isomerization of the acetylene 171. In fact, the irradiation of 2-thienyl-trimethylsilylacetylene gave 3-thienyl-trimethylsilylacetylene. 

TMS group is used for protection of terminal alkynes. However, alkynylsilanes themselves can be used for the coupling with aryl and alkenyl triflates using Pd-CuCl as a catalyst [74], Thus the internal alkyne 160 is prepared by stepwise reactions of two different triflates 157 and 159 with trimethylsilylacetylene (134) via 158. 

Coupling of vinyl bromides with alhynesThe P-bromide of ethyl (Z)-2,3-dibromopropenoate (1) couples selectively with trimethylsilylacetylene in the presence of Cul, Pd(0), and a base to provide the bromoenyne 2 in 86-90% yield. 

Scheme 14 Aryl coupling of trimethylsilylacetylene via a palladium-catalyzed Sonogashira protocol...

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