Imidazole, Markovnikov addition

A basic ionic liquid, l-methyl-3-butylimidazolium hydroxide ([bmIm]OH) and l-butyl-3-methyl-methylimidazolium tetrafluoroborate ([bmim]BF4), has been introduced as a catalyst and reaction medium for the Markovnikov addition of imidazoles 116 to vinyl esters 115 under mild conditions to give imidazoesters 117 <06JOC3991 06TL1555>. A series of (nitroimidazolyl)succinic esters and diacids were prepared from the Michael-type addition of the nitroimidazole to the a,P-unsaturated ester <06S3859>. 

Imidazolide ionic liquids [l-butyl-3-methylimidazoline hexafluorophosphole (Bmin)]Im (2mol%) have been reported to catalyse Markovnikov addition of, for example, imidazole to vinyl acetate AcOCH=CH2 at room temperature in Ih. Experimental results showed that a hydrogen bond is not formed between [Bmimjim/imidazole and the vinyl ester, and its existence is not a prerequisite for the reaction to occur. 

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 FBr to l-trityl-4-vinyl-l/7-imidazole 756 occurs with Markovnikov regioselectivity to produce 757 (Scheme 186). Elimination of HBr (giving 758) followed by fluorobromination provides 759. The bromide is converted into azide 760, which is reduced to 3, 3-difluorohistamine 761. In contrast, functionalization of l-trityl-4-formyl-l/7-imidazole (cyanohydrin/DAST MeNOz) does not yield useful intermediates for the preparation of 761 <2001JOC4687>. The FBr addition/HBr elimination is compatible with hydroxyl (but not carboxyl) group 762, which is employed in the synthesis of 763 en route to P-fluorourocanic acids 764 <2002JOC3468>. 

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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