Remote meta C–H bond functionalization of 2-phenethylsulphonic acid and 3-phenylpropanoic acid derivatives

Abstract

This discovery illustrates selective meta C-H bond activation from multiple non-equivalent C-H bonds present in medicinally relevant arylethanesulfonic acid and the 2-arylpropanoic acid moiety using weakly coordinating nitrile as a directing group. Transformation of the meta olefinated compounds to important organic molecules has been demonstrated. Efforts were made to obtain mechanistic detail of the meta C-H bond functionalization reaction.

Accessing Remote meta‐ and para‐C(sp2)−H Bonds with Covalently Attached Directing Groups

“…[31] phenethyl sulfonate (R = H) meta-olefination [32] aryl alcohol and acid (R = OMe) meta-olefination [33] aryl sulfonates (R = OMe) meta-silylation meta-germanylation [34] benzylsulfonyl esters phenylacetic acids meta-olefination [36] benzyl sulfonyl esters meta-olefination [41] benzyl sulfonates meta-cyanation meta-alkylation [43] [44] aryl sulfonates meta-cyanation meta-alkylation meta-alkenylation [43] [44] [44] phosphonate benzyl phosphonates meta-olefination meta-acetoxylation meta-hydroxylation [37] Angewandte Chemie Reviews…”

“…Thep otential of this procedure was demonstrated by sequential ortho-and meta-olefination of phenethylamine derivatives (31)(32)(33)(34)(35)(36). Finally,the directing group was removed under acid hydrolysis to afford meta-substituted phenylethylamine 37.…”

“…[32] Both carbonyl and sulfonyl linkers proved useful for tethering the substrate to the director. [32] Both carbonyl and sulfonyl linkers proved useful for tethering the substrate to the director.…”

Carboxy Group as a Remote and Selective Chelating Group for C−H Activation of Arenes

“…To examine our hypothesis, we synthesized the hydrocinnamic amide 1 a H as the substrate and chose olefination as the model reaction (Table ). After screening a series of reaction conditions, we were very glad to obtain 18 % yield of remote selective, meta ‐olefinated products using Pd(OAc) 2 in HFIP (hexafluoroisopropanol) at 80 °C for 24 h (entry 1) . Notably, only traces of olefination products at the o 1 ‐ and p ‐positions of the target phenyl ring were obtained ( m : o 1 =91:9 and m : p= 95:5, see the Supporting Information for the synthesis of the isomers).…”

“…With the optimized reaction conditions in hand, we examined the scope of this protocol with hydrocinnamic acid derivatives and related arenes (Table ) . Good yield of the isolated product was obtained with the model substrate using either ethyl or n ‐butyl acrylate ( 2 a F and 2 b F ), and the reaction was compatible with substrates bearing substituents at the ortho ‐, meta ‐, and para ‐positions ( 2 c F – g F ) with generally good meta ‐selectivity.…”