Computational rationalization of the selective C–H and C–F activations of fluoroaromatic imines and ketones by cobalt complexes

Abstract

While selective C-H and C-F activations of fluoroaromatic imines and ketones with transition metal complexes supported by PMe3 have been successfully achieved in recent publications, insight into the molecular mechanism and energetics of those reactions is still lacking. Focusing on three typical substrates, 2,6-difluorobenzophenone imine (A) and 2,6-difluorobenzophenone (B), and 2,4'-difluorobenzophenone (C), the present work theoretically studied their C-H and C-F cyclometalation reactions promoted by the activator Co(PMe3)4 or CoMe(PMe3)4. It is found that reaction A + Co(PMe3)4 favors the C-F activation, reaction A + CoMe(PMe3)4 prefers the C-H activation, whereas both the C-H and C-F activation pathways may be viable for reactions B + CoMe(PMe3)4 and C + CoMe(PMe3)4. The experimentally observed C-H and C-F cyclometalation products have been rationalized by analyzing the thermodynamic and kinetic properties of two activation pathways. From calculated results combined with the experimental observations, we believe that three factors, i.e. the oxidation state of the metal center in the activators, the anchoring group of substrates, and substituted fluoroatom counts of the aromatic ring in substrates, affect the selectivity of C-H and C-F activations of fluoroaromatic ketones and imines. Calculated results are enlightening about the rational design of activators and substrates of fluoroaromatic imines and ketones to obtain the exclusive C-H or C-F bond activation product.

Copper‐Catalyzed Deoxygenative C‐2 Amination of Quinoline N‐Oxides

“…[7] With O-benzoylhydroxylamines as the electrophilic reagents, [8] Cu II -catalyzed direct C-H bond amination of quinoline N-oxides at C2-position has been achieved by Li and Wu et al (Scheme 1d). [9] To cleave the N-O bond, however, the additional reductant such as PCl 3 is still required in these examples. Recently, Zhao and co-workers have developed a new method for the preparation of 2-aminoquinolines by H-phosphonate.…”

New Perspectives in the Indole Ring Functionalization using 2‐Indolylmethanols

“…Te rtiary 2-indolylmethanols 33 react with cyclic enaminones 34 in the presenceo fp entafluorobenzoic acid leading to compounds 36 showing amarked preference for C-3r ing addition (Scheme 9). [17] Thes teric hindrance around the exocyclic electrophilic site is probably responsible for the observed regioselectivity in these reactions.A ctivationo ft he nucleophile 34 is probably providedb yh ydrogenb onding of the NH with the acyl oxygeno ft he catalyst. This assumption seems confirmed by the reducedy ield obtained in this reactionu sing N,N-disubstituted enaminones 34.…”

Recent Advances in Pd‐Catalyzed Cross‐Coupling Reaction in Ionic Liquids

“…Guided by this, we successfully accomplished a cascade annulation/alkynylation se-quence involving 2-alkynylanilines and terminal alkynes and catalyzed by NHC-Pd species (NHC = N-heterocyclic carbene) 40 to afford free (NH)-3-alkynylindole derivatives 41 in [C 2 OHmim]Cl (Scheme 20). [42] The newly developed NHC-Pd II catalytic system efficiently catalyzed the cascade annulation/ alkynylation sequence at 60°C over 8 h in the open air. The free (NH)-3-alkynylindole derivatives were obtained in yields of up to 89 % with 1 mol-% catalyst loading.…”