Ruthenium(ii)-catalyzed synthesis of CF₃-isoquinolinones via C–H activation/annulation of benzoic acids and CF₃-imidoyl sulfoxonium ylides

Abstract

A ruthenium(II)-catalyzed C−H activation/annulation reaction of benzoic acids and CF3-imidoyl sulfoxonium ylides enabled by weak O-coordination has been achieved. A series of 3-trifluoromethylisoquinolinones were synthesized in 37-75% yields under redox-neutral...

Enantioselective Access to C-N Axially Chiral Isoquinolones via Dynamic Kinetic Transformation of Carbene Reagents: Unique Chiral Induction Enabled by Dual Role of the Catalyst

“…Our design boils down to development of new coupling reagents that are both bulky and reactive. To reconcile these seemingly contradictive criteria, we employed a bifunctional carbene reagent such as CF3-imidoyl sulfoxonium ylides (TFISYs) [57][58][59][60][61][62][63][64][65] bearing a proximal nucleophilic imine nitrogen as well as a bulkyl N-aryl group (Scheme 1c). Consequently, a secondary amide bearing an electrophilic directing group [66][67][68][69][70][71] was applied as the C-H substrate.…”

“…The absolution configuration of product 51 has been confirmed to be (R) by X-Ray crystallography (CCDC2211789). The CF3 group in the imidoyl sulfoxonium ylide was also successfully extended to C2F5 and other difluoalkyls(61)(62)(63)(64) with no loss of enantioselectivity (89-94% ee).In contrast, no reaction occurred when the CF3 was replaced by a Ph group, suggesting necessity of EWG-activation of the carbene reagent. The rotational barrier of representative products (3, 51 and 59) along the C-N axis has been determined, with the ∆ ranging from 28.7 to > 37 kcal/mol and a bulkier o-substituent results in higher barrier (Scheme 2).…”

Ruthenium-Catalyzed Hydroxyl-Directed peri-Selective C–H Activation and Annulation of 1-Naphthols with CF3–Imidoyl Sulfoxonium Ylides for the Synthesis of 2-(Trifluoromethyl)-2,3-dihydrobenzo[de]chromen-2-amines

“…12 They also demonstrated a ruthenium-catalyzed C−H activation/annulation of benzoic acids and TFISYs for the synthesis of 3-(trifluoromethyl)isoquinolinones. 13 Prompted by the above pioneering work about TFISYs and our ongoing work on the efficient synthesis of trifluoromethyl-containing heterocycles using trifluoromethyl synthons, 14 we herein present a ruthenium-catalyzed hydroxyl-directed peri-selective C−H activation and cascade annulation reaction of 1-naphthols with TFISYs, which provides facile access to 2-(trifluoromethyl)-2,3-dihydrobenzo[de]chromen-2-amines with high efficiency.…”

“…Competition experiments between differently substituted TFISYs or 1-naphthols suggested the preferential reactivity of electron-rich TFISYs and electron-deficient naphthols, which was consistent with the previously reported Ru­(II)-catalyzed peri -C–H activation reactions , and cascade annulations with TFISYs . On the basis of the mechanistic studies and previous reports of Ru­(II)-catalyzed directed C–H activation reactions, ,,, a plausible catalytic cycle was proposed (see Scheme S2 in the Supporting Information).…”

Formal [4+1] Annulation of Azoalkenes with CF3-Imidoyl Sulfoxonium Ylides and Dual Double Bond Isomerization Cascade: Synthesis of Trifluoromethyl-Containing Pyrazole Derivatives

“…The CF 3 -substituted imidoyl sulfoxonium ylides (TFISYs) are regarded as a kind of versatile trifluoromethyl-containing synthon and have been applied in the assembly of different trifluoromethyl-substituted heterocycles . Recently, Cheng and co-workers reported a series of synthetic methods using TFISYs with various coupling partners to lead to trifluoromethyl-substituted pyrroles, pyridines, and isoquinolinones . We envision that TFISYs could serve as an ideal C1 source to participate in the [4+1] annulation with azoalkenes for producing the biologically important trifluoromethyl-decorated pyrazole derivatives.…”