Multicomponent coupling alkyne termination

Several heterogeneous catalysts have been shown to effect related multicomponent couplings. These include cross-linked polymeric ionic liquid material-supported copper (Cu-CPSIL), silica-dispersed CuO (CuO/Si02), and imidazolium-loaded Merrifield resin-supported copper (Cu-PSIL), all of which can be used in water at room temperature to arrive at 1,4-disubstituted-1,2,3-triazoles from alkyl halides, NaNs, and terminal alkynes. Each can be filtered and reused several times with minimal loss of efficacy. Multistep flow synthesis, specifically including generation of underused vinyl azides and their subsequent click conversions to vinyl triazoles, has also been reported. ... 

Based on the aforementioned amination process, Xi developed a one-pot synthesis of 2-alkynylindoles 36 involving the multicomponent coupling of o-bromo-(2,2-dibromovinyl)ben-zenes 35, arylamines, and terminal alkynes. The reaction is proposed to proceed through a Pd-catalyzed Sonogashira coupling leading to a monoalkynylated product XIV, followed by an intermolecular Buchwald-Hartwig amination to XV and a... 

Lu has demonstrated that this aryl halide-mediated cydization can be coupled with the generation of the alkynylaniline derivative via Sonogashira coupling, providing a multicomponent route to build up indoles from anilides, terminal alkynes and aryl halides (Scheme 6.15) [19]. Similar approaches have been applied to the construction of benzofurans [20] and substituted fiirans [21]. 

An alternative approach to multicomponent heterocycle synthesis involves the use of palladium catalysis to construct keto-alkynes for cycloaddition reactions. Muller has demonstrated the power of this approach in the construction of a range of aromatic heterocycles. For example, the palladium-catalyzed coupling of acid chlorides with terminal alkynes provides a method to assemble 36. The trapping of this substrate can provide routes to aromatic heterocycles. As an example, the addition of amidines provides a multicomponent synthesis of pyrimidines (Scheme 6.69) [97]. This same substrate 36 is available via the carhonylative coupling of aryl halides with terminal alkynes, providing a four-component synthesis of pyrimidines (98j. 36 can also be employed in 1,3-dipolar cydoaddition reactions. For example, cydoaddition... 

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