Structure-Selectivity Relationship in Ruthenium-Catalyzed Regio- and Stereoselective Addition of Alkynes to Pyrazoles: An Experimental and Theoretical Investigation Uttam Kumar Das, Subhajit Mandal, Anakuthil Anoop,* and Manish Bhattacharjee* Department of Chemistry, Indian Institute of Technology, Kharagpur 721 302, India * S Supporting Information ABSTRACT: Ruthenium(II) complexes, [Ru(dppe)(PPh 3 )- (CH 3 CN) 2 Cl][BPh 4 ] {dppe = diphenylphosphinoethane} (1) and [Ru(dppp) 2 (CH 3 CN)Cl][BPh 4 ](2) {dppp = diphenyl- phosphinopropane}, are efficient catalysts for vinylation of pyrazoles by alkynes. While the 1-catalyzed reaction is trans- selective, the corresponding 2-catalyzed reaction is cis-selective. The experimental results have been rationalized by density functional theory calculations. ■ INTRODUCTION N-Vinyl azoles have attracted great attention over the past few years because of their use in the synthesis of polymeric materials that show catalytic as well as photorefractive properties. 1 Some of the compounds also show antifungal activities. 2 It has been shown in the literature that palladium 3 and mercury 4 complexes can catalyze vinylation of azoles by vinyl bromide. However, both methods require extreme conditions. More recently, coupling of vinyl bromide/iodide and amines mediated by copper(I) in the presence of ligands and a large amount of bases such as Cs 2 CO 3 5 have been developed, and the same method has been used for vinylation of azoles. 1a,d,6 Most of these methods either require harsh conditions or a long reaction time. Moreover, some of these methods require high catalyst loading. A recent report deals with copper(I)-catalyzed reactions with only 5 mol % of catalyst loading, but in most of the cases, only vinyl iodide was found to be effective. 7 Moreover, in almost all the reported methods, only (E)-vinyl products were obtained. It may be noted that coupling of vinyl bromide/iodide with amines is not an atom economical, environmentally friendly, and economical method because a large amount of alkali halide is produced and vinyl halides are expensive. It was reported that Ru 3 (CO) 10 can catalyze vinylation of azoles by alkynes; however, a mixture of products was obtained. 8 In a recent report, the authors found that Ag(NO 3 )/Ag(OTf) can catalyze single and double addition of pyrazole to alkynes. However, for single addition, the catalyst loading is high and the reaction conditions are harsh (130 °C, PhCl). 9 Azole addition to terminal alkynes is one type of hydro- amination that affords a number of possible products. Selectivity of the reaction is a central issue. Gooßen and co-workers reported that [(cod)Ru(met) 2 ]affords (E)-enamides from terminal alkynes and secondary amides in the presence of a tri-n-butylphosphine (P(n-Bu) 3 ) ligand, but the stereoselectivity changes to the corresponding (Z)-enamides when a bulkier ligand such as bis(dicyclohexylphosphino)methane is used. 10 Often, the nature of the substrate determines the regio- and stereoselectivity of a reaction. Control of regio- and stereo- selectivity by the nature of the catalyst is not very common. So, catalyst-controlled product stereoselectivity is a challenge. Thus, selectivity is one of the challenging aspects in the addition reaction of terminal alkynes. We have been interested in the synthesis and catalytic activities of ruthenium phosphine com- plexes with hemilabile ligands, where coordinatively unsaturated species can be generated in solution. 11 Recently, in a preliminary communication, we reported the synthesis and structure of [Ru(dppe)(PPh 3 )(CH 3 CN) 2 Cl][BPh 4 ] {dppe = diphenylphos- phinoethane} (1) and showed that 1 can catalyze the addition of terminal alkynes to azoles in a highly regiospecific as well stereo- selective manner, and primarily (E)-addition products were obtained. 12 In another recent report, we described the synthesis and structure of [Ru(dppp) 2 (CH 3 CN)Cl][BPh 4 ] {dppp = diphenylphosphinopropane} (2), which can catalyze the oxidative coupling of terminal alkynes in the presence of a catalytic amount of Ag(NO 3 ). 13 We were interested in exploring this catalyst-structure-dependent stereospecificity of the reaction so that the (Z)-addition product can be obtained. Herein, we report the structure-selectivity relationship in the vinylation of pyrazoles by alkynes catalyzed by [Ru(dppe)- (PPh 3 )(CH 3 CN) 2 Cl][BPh 4 ] 1 and [Ru(dppp) 2 (CH 3 CN)Cl]- [BPh 4 ] 2. Details of the 1-catalyzed reaction are described here. In addition, the experimental results have been rationalized by Received: June 11, 2014 Published: October 13, 2014 Article pubs.acs.org/joc © 2014 American Chemical Society 9979 dx.doi.org/10.1021/jo502151z | J. Org. Chem. 2014, 79, 9979-9991