Ru(II)‐Catalyzed Hydroarylation of in situ Generated 3,3,3‐Trifluoro‐1‐propyne by C−H Bond Activation: A Facile and Practical Access to β‐Trifluoromethylstyrenes

Abstract

In this study, a practical and straightforward synthesis of β-(E)-trifluoromethylstyrenes by ruthenium-catalyzed C-H bond activation was developed. The readily available and inexpensive 2bromo-3,3,3-trifluoropropene (BTP), a non-ozone depleting reagent, was used as a reservoir of 3,3,3-trifluoropropyne. With this approach, the monofunctionalization of a panel of heteroarenes was possible in a safe and scalable manner (23 examples, up to 87% yield). Mechanistic investigations and density functional theory (DFT) calculations were also conducted to get a better understanding of the mechanism of this transformation. These studies suggested that 1) a cyclometallated ruthenium complex enabled the transformation, 2) this latter exhibited high efficiency in this transformation compared to the commercially available [RuCl2(p-cymene)]2 and 3) the mechanism proceeded through a bis-cyclometallated ruthenium intermediate for the carboruthenation step.

Copper-Catalyzed Synthesis of 4-CF3-1,2,3-Triazoles: An Efficient and Facile Approach via Click Reaction

“…We speculated that this process is not 1,3-dipolar cycloaddition of BTP with azide. Based upon experiments and the literature [ 81 , 82 , 83 , 84 ], a possible pathway was proposed as Scheme 3 . Firstly, BTP is converted to TFP by treatment with DBU as the base.…”

“…In contemplating possible methods to carry out these click reactions, we recognized that 2-bromo-3,3,3-trifluoropropylene (BTP) is a commercially available reagent [ 68 , 69 , 70 , 71 , 72 ], and that its [3+2]-cycloaddition reactions have been employed to produce CF 3 -substituted pyrazoles [ 73 , 74 , 75 , 76 ], -isoxazoles [ 77 ] and -pyrroles [ 78 ]. Particularly informative are the observations that BTP can be readily transformed to TFP by treatment with bases [ 79 , 80 , 81 , 82 , 83 ] like i -Pr 2 NLi and 1,8-diazabicyclo[5.4.0]undec-7-ene DBU, and that compared to gaseous TFP, BTP is an inflammable, storage-stable and easily handled liquid. Regrettably, it was inscrutably neglected to utilize BTP in click reactions to synthesize the 4-trifluoromethyl 1,2,3-triazoles.…”

Ruthenium-catalyzed hydroarylation reactions as the strategy towards the synthesis of alkylated arenes and substituted alkenes

“…Besset et al recently reported an important strategy for synthesizing this scaffolds by the in situ generation of 3,3,3-trifluro-1-propyne from inexpensive non-toxic 2-bromo-3,3,3-trifluropropene (BTP) and the Ru( ii )-catalyzed hydroarylation of this alkyne with the aryl species of our interest. 29 The reaction conditions were found to be optimum with 5 mol% [RuCl 2 ( p -cymene)] 2 as the catalyst, 2.0 equiv. t BuONa as the base and DMF as the solvent at 90 °C for 24 h with 3-methyl-2-phenyl pyridine as the model substrate.…”

Multi-substituted trifluoromethyl alkene construction via gold-catalyzed fluoroarylation of gem-difluoroallenes

“…[25][26][27] As such, the development of efficacious synthetic strategies for expedient assembly of sophisticated triuoromethyl alkenes, especially those that are not readily available by using the extant methods, has evoked enormous interest from multi-discipline. [27][28][29] In the context, the Witting-type olenation [30][31][32] and transition-metalcatalyzed cross-coupling reactions 26,27,[33][34][35] evolve to be the state of the art, despite the remaining issues such as strongly basic reaction conditions, volatile and expensive tri-uoromethyl reagents, and poor stereoselectivities. With our continuing interest in the uoroarylation of p systems, 15,21,36,37 we would like to report herein our latest advancement in this territory (Scheme 1d).…”