The [3+2] Annulation of CF3-Ketimines by Re Catalysis: Access to CF3-Containing Amino Heterocycles and Polyamides

Abstract

Transition metal catalyzed [3 + 2] annulation of imines with double bonds via directed C-H activation offers a direct access to amino cyclic motifs. However, owing to weak coordination and steric hindrance, trifluoromethylated ketimines have been an unaddressed challenge for TM-catalyzed annulations. Here, a rhenium-catalyzed [3 + 2] annulation of trifluoromethylated ketimines with isocyanates via C(sp 2 )-H activation has been disclosed. This approach provides an efficient platform for rapid access to a privileged library of CF 3 -containing iminoisoindolinones and polyamides by utilizing challenging CF 3 -ketimines as the annulation component. The capability of gram scale synthesis, the post-functionalization of the cyclization adduct, the derivation of complex natural molecules and the facile synthesis of polyamides highlight a diversity of synthetic potential of the current methodology.

Defluorinative Carboimination of Trifluoromethyl Ketones

“…B) Reaction conditions for step 2: step 1 was complete, then removal of Ag catalyst and toluene from the residue were added NaBH4 (2.5 equiv) and CH3OH (2 mL). containing azaheterocycles containing a quaternary carbon center (51). Moreover, the difluoromethyl ketone 83 and the dibromide 84 were obtained in high yield by the treatment of 3 with silica gel and hydrobromic acid, respectively (52).…”

Synthesis of β-CF3 β-Amino Esters with an Indane Backbone by Rhenium-Catalyzed [3+2] Annulation

“…We first investigated the model annulation reaction by coupling 2,2,2-trifluoro-N,1-diphenylethan-1-imine (1a) with methyl acrylate (2a) using the previously established reaction conditions to which isocyanates were exposed. 9 To our delight, the expected CF 3 β-amino ester (3a) was formed in 58% yield with 17% of imine recovered (Table 1). The subsequent screening of a variety of precatalysts such as Re, Mn, Ru, Fe, Rh, Pd, Cu, and W suggested that Re 2 (CO) 10 exhibited exclusive catalytic performance versus others.…”

“…Inspired by the leading works on the synthesis of β-fluoroalkylated β-amino acid derivatives (Scheme , top) starting from β-fluoroalkylated acrylates, fluoroalkyl imines, , fluorinated imidoyl chlorides, or α-trifluoromethyl N -tert-butanesulfinyl hemiaminals, and the fact that C–H activation has been emerged as a powerful means to provide fluorinated amino acid analogues, we then envisioned that transition metal-catalyzed annulation of CF 3 -ketimines with acrylates as the acceptor via C–H activation would generate cyclic β-CF 3 β-amino esters, which constitute an important precursor for fluorinated β-amino acid synthesis. The proposed strategy features the following advantages: (1) forging a trifluoromethylated quaternary carbon center, (2) no employment of an expensive fluorinating reagent, and (3) the easily accessible annulation partner trifluoromethylated ketimines.…”

“…We first investigated the model annulation reaction by coupling 2,2,2-trifluoro- N ,1-diphenylethan-1-imine ( 1a ) with methyl acrylate ( 2a ) using the previously established reaction conditions to which isocyanates were exposed . To our delight, the expected CF 3 β-amino ester ( 3a ) was formed in 58% yield with 17% of imine recovered (Table ).…”

Merging Imidazolidines with a Trifluoromethylated Tetrasubstituted Carbon through Tungsten Catalyzed 1,3-Dipolar Cycloaddition

“…However, owing to the normal challenging issues associated with the construction of a fully substituted carbon and the steric hindrance and electrostatic repulsions arising from the effect of the CF 3 group, the 1,3-dipole cycloaddition between acyclic trifluoromethylated ketimines and certain 1,3-dipoles remains unaddressed, although the CF 3 group has a strong electronic effect on the electrophilic character of dipolarophiles, which would deliver N -heterocycles bearing a CF 3 -tetrasubstituted carbon. As our continuous interest in the annulations of CF 3 -ketimines, we are presenting the first tungsten-catalyzed 1,3-dipole cycloaddition of acyclic CF 3 -ketimines with N -benzyl azomethine ylide, providing a range of novel trifluoromethylated imidazolidines with high efficiency (Scheme , bottom). These newly forged motifs with an imidazolidine backbone and a trifluoromethylated tetrasubstituted carbon might have potential biologically active profiles.…”