Trimethylsilylacetylene, cross-coupling

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... 

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.

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... 

The cross-coupling of a resin-bound iodobenzoic acid 76 with trimethylsilylacetylene followed by TBAF desilylation provides a polymer-supported arylacetylene. Treatment with an aldehyde and a secondary amine in dioxane in the presence of CuCl catalyst results in the generation of resin-bound propargylamines. The final products 77 are cleaved from the resin and obtained in excellent yields and purity (Scheme 30) " ... 

The most commonly used protecting group for acetylenes is the trimethylsilyl (TMS) group.f Thus, commercially available trimethylsilylacetylene provides an excellent starting material for the synthesis of aryl and alkenyl acetylenes. Triisopropylsilyl groups are also useful for the step wise deprotection with TMS groups (Scheme 37). Cross-coupling of aryl or alkenyl halides with trimethylsilylacetylene proceeds in the presence of a Pd catalyst and Cul, followed by treatment with dilute aqueous or in... 

Substituents were also introduced on the pyridopyrimidinone ring via palladium-mediated cross-coupling reactions as outlined in Figure 2. Crosscoupling of 7-bromo-2-propoxy-3-propylpyridopyrimidinone la-1 (made by the method in Figure 1) with phenyl boronic acid, potassium cyanide or trimethylsilylacetylene (followed by desilylation with base) gave the phenyl, acetylenic and cyano substituted products la-2, la-3 and la-4, respectively. 

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). 

Poly[2,5-ethynylene-(thieno[3,2-h]thiophenediyl)ethynylene] (109) was constructed from dibromo-TT (56) via Sonogashira cross-coupling with trimethylsilylacetylene providing 69 then, after desilylation, chemical polymerization of 70 using CuCl and O2 gave 109 (Scheme 24) [18]. 

Dibromothiophene (14) can be converted into 2 in two steps in an overall yield of 39% (Scheme 32). Sonogashira cross-coupling with trimethylsilylacetylene provided 146. Transmetallation then addition of elemental sulfur gave the corresponding thiolate, thermal cyclization of which afforded thieno[3,4-b]thio-phene (2) as a colorless oil [55]. Using phenylacetylene instead of trimethylsilylacetylene led to 2-phenylthieno[3,4-h]thiophene in 19% yield from the dihalide [54]. 

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