Rhodium-Catalyzed sp² C–H Acetoxylation of N-Aryl Azaindoles/N-Heteroaryl Indolines

Abstract

A silver- and copper-free rhodium-catalyzed C-H acetoxylation reaction of azaindoles has been achieved at near ambient temperature employing PIDA as a nonmetallic acetoxy source. The method is highly selective, efficient, and scalable and requires acetic anhydride as the sole additive. The scope of the reaction has been successfully tested with a wide array of medicinally important heterocyclic scaffolds with diverse functional group tolerance. A series of kinetic experiments was conducted to gain detailed insight into the reaction mechanism. The methodology developed could be successfully expanded for C7-acetoxylation of indoline derivatives using pyrimidine as a detachable directing group for the synthesis of 7-hydroxyindole.

RhIII‐Catalyzed Directed Selective C7‐Hydroxylation and Acetoxylation of Indolines

“…On the basis of the above experimental results and previous reports,,, the plausible mechanism of C7‐acetoxylation and C7‐hydroxylation reactions of indolines is proposed (Scheme ). First, [Cp*RhCl 2 ] 2 is transferred to the active catalyst [Cp*Rh(OAc) 2 ] ( A ) in the presence of super stoichiometric acetate anion of PhI(OAc) 2 or Ac 2 O.…”

“…‐ Despite these attractive processes, all the reactions are limited to C−C, C−N, less commonly, C−S(Se) bond formation. There are only a few reports on the catalytic C‐7 acetoxylation of indolines and is no report on C‐7 hydroxylation of indolines up to now. C−O bonds are ubiquitous in natural products, pharmaceuticals, biologically active compounds, fragrances, and polymers .…”

“…C−O bonds are ubiquitous in natural products, pharmaceuticals, biologically active compounds, fragrances, and polymers . In the past decade, transition‐metal‐catalyzed chelation‐assisted C(sp 2) ‐O bond formation attracted much interest of researchers, some examples of chelation‐assisted C−H oxygenation have been reported by using palladium, less commonly, copper,, ruthenium, and rhodium ,. In 2017, Deb and coworkers had a simple probe using cationic Rh III catalyst on acetoxylation of indolines with prolong time and depressed yield .…”

“…In the past decade, transition‐metal‐catalyzed chelation‐assisted C(sp 2) ‐O bond formation attracted much interest of researchers, some examples of chelation‐assisted C−H oxygenation have been reported by using palladium, less commonly, copper,, ruthenium, and rhodium ,. In 2017, Deb and coworkers had a simple probe using cationic Rh III catalyst on acetoxylation of indolines with prolong time and depressed yield . Very recently, Koley and coworkers reported Cu(I)‐catalyzed site selective acyloxylation of indolines using O 2 as the oxidant .…”

Cobalt‐Catalyzed Directed sp2 C−H Acetoxylation of Arenes Employing Mn(OAc)3 ⋅ 2H2O as Acetoxy Source

“…We have recently reported a rhodium‐catalyzed mild C−H acetoxylation reaction as a part of a continuing research endeavour in transition metal catalyzed C−H functionalizations . Significant progress has been made exploiting various acetoxy sources such as Cu(OAc) 2 , AgOAc, PhI(OAc) 2 , AcOH etc.…”