Pyrrole Markovnikov addition

Gunnoe has also reported examples of catalytic aromatic alkylation using a ruthenium complex and olefins. With propylene and other terminal olefins, a 1.6 1 preference for anti-Markovnikov addition was seen. The proposed mechanism involved olefin insertion into the metal-aryl bond followed by a metathesis reaction with benzene to give the alkylated aromatic and a new metal-phenyl bond (Equation (26)). DFT calculations supported the proposed non-oxidative addition mechanism. The work was extended to include catalytic alkylation of the a-position of thiophene and furan. With pyrrole, insertion of the coordinated acetonitrile into the a-C-H bond was observed. Gunnoe has also summarized recent developments in aromatic C-H transformations in synthesis using metal catalysts. ... 

Examples of palladium- and rhodium-catalyzed hydroaminations of alkynes are shown in Equations 16.90-16.92 and Table 16.9. The reaction in Equation 16.90 is one of many examples of intramolecular hydroaminations to form indoles that are catalyzed by palladium complexes. The reaction in Equation 16.91 shows earlier versions of this transformation to form pyrroles by the intramolecular hydroamination of amino-substituted propargyl alcohols. More recently, intramolecular hydroaminations of alkynes catalyzed by complexes of rhodium and iridium containing nitrogen donor ligands have been reported, and intermolecular hydroaminations of terminal alkynes at room temperature catalyzed by the combination of a cationic rhodium precursor and tricyclohexylphosphine are known. The latter reaction forms the Markovnikov addition product, as shown in Equation 16.92 and Table 16.9. These reactions catalyzed by rhodium and iridium complexes are presumed to occur by nucleophilic attack on a coordinated alkyne. 

Using the binuclear ruthenium(II) catalyst [RuBr2(CO)2(PPh3)]2 Wai Yip Fan succeeded to achieve the alkenylation of pyrroles with terminal alkynes under mild conditions at 50°C. This catalyst leads to the reverse regioselectivity for hydroheteroarylation of alkynes and the dialkenylation of pyrrole can be controlled. The mechanism likely involves an electrophilic activation of the alkyne by the Ru (II) species favouring the nucleophilic Markovnikov addition of pyrrole to the alkyne internal carbon [(Eq. 78)] [162]. 

An efficient protocol for Markovnikov-type addition of N-hclcrocycles (imidazole, pyrazole, pyrrole, etc.) to the electron-rich double bond of vinyl esters using ionic liquid as a catalyst has been reported.40... 

Addition of primary amine to a 1,4- or 1,5-diyne could be accomplished using titanium complex Ti(NMe2)2(dpma), resulting in an imine-yne that can undergo cyclization to the pyrrole derivatives. The Markovnikov hydroamina-tion products of 1,4-pentadiyne could undergo 5-endo-dig cyclization to yield a 2-methylpyrrole. Meanwhile, Markovnikov hydroamination of 1,5-hexandiyne would yield an imine-yne that could undergo 5-exo-dig cyclization to a 2,5-dimethylpyrrole [314] (Scheme 14.135). 

The cesium hydroxide-promoted addition of benzimidazole to phenylacetylene proceeded with exclusive anti-Markovnikov regioselectivity and complete stereoselectivity for the formation of the Z-isomer (Scheme 3.132) [142]. Similar reactivity was obtained for pyrrole and imidazole however, acyclic secondary amines such as diphenylamine or phenytmethylamine afforded mixtures of the stereoisomers. It should be noted that these additions were still regioselective for the anti-Markovnikov product. In related work, the base-assisted synthesis of enamines through the addition of indole derivatives to TMS-protected alkynes has been achieved using KOH as the promoter (Scheme 3.133) [143]. 

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