CC Coupling Reactions of Superstrong CF₃ Groups with C(sp²)–H Bonds: Reactivity and Synthetic Utility of Zero‐Valent Niobium Catalyst

Abstract

It was found that zero-valent niobium is an efficient catalyst for the intramolecular C-C coupling reactions of o-aryl and o-alkenyl alpha,alpha,alpha-trifluorotoluene derivatives. The superstrong C-F bonds of CF3 groups and neighboring C(sp2)-H bonds were doubly activated, and fluorenes and indenes were obtained in good yields. The niobium fluorocarbenoid species is proposed to be the key intermediate.

Niobium‐Catalyzed Activation of Aryl Trifluoromethyl Groups and Functionalization of CH Bonds: An Efficient and Convergent Approach to the Synthesis of N‐Heterocycles

“…[7,9,10] The slow addition of LiAlH 4 was necessary to achieve high yields of fluorenes such as 16. When the reaction was performed in an aromatic solvent, intermolecular C À C bond formation occurred to produce mixtures of mono-and diarylated fluorenes 18 and 19.…”

“…[16] The mechanism for this transformation was proposed to occur through a carbenoid reactive intermediate (Scheme 7). [9,11] The niobium catalyst is generated by reduction using sodium aluminum hydride. This species defluorinates the aryl trifluoromethyl group to afford fluorinesubstituted carbenoid 28, which reacts with the proximal CÀ H bond to afford indoline 29.…”

“…[*] T. G. Akiyama and co-workers discovered that CF 3 groups could be reduced by zero-valent niobium complexes. [7][8][9] The required niobium catalyst was generated through exposure of NbCl 5 to an excess of lithium aluminum hydride. While hydro-defluorination of a,a,a-trifluorotoluene derivatives was efficient, the functional group tolerance of the method appeared limited to nonreducible substituents (Scheme 4).…”

Expedient Synthesis of N‐Fused Indoles: A CF Activation and CH Insertion Approach

“…Insertion reactions of a niobium fluorocarbenoid center, which is generated from a CF 3 group attached to an aromatic nucleus, into a C(sp 2 )ÀH bond were developed recently by our group. [11][12][13] Scheme 3 shows precursors which were prepared in good yields mainly by the Buchwald amination reaction (see the Supporting Information for details). [10] Notably, CF 3 groups, which would generate the key carbenoid centers, were not affected by the CÀN coupling conditions.…”

Niob‐katalysierte Aktivierung von Aryltrifluormethylgruppen und Funktionalisierung von C‐H‐Bindungen: ein effizienter, konvergenter Ansatz zur N‐Heterocyclensynthese

“…[7,9,10] [11] Arylamine wie 20 werden von niedervalentem Niob reduziert, wobei Gemische des Indolins 21 und des Indols 22 erhalten werden [Gl. (1)].…”