Iridium‐Catalyzed Direct CH Amidation with Weakly Coordinating Carbonyl Directing Groups under Mild Conditions

Abstract

An iridium-catalyzed direct C-H amidation of weakly coordinating substrates, in particular of those bearing ester and ketone groups, under very mild conditions has been developed. The observed high reaction efficiency was achieved by the combined use of acetic acid and lithium carbonate as additives.

2.9 C—N Bond Formation by C—H Functionalization via Metal-Catalyzed Nitrene Insertion

“…Purification via MPLC provided the indole as a white solid. [39] OMe OEt 4-Tol 98 [39] OH OEt 4-Tol 93 [39] H [42] H Me 99 [42] H OMe 76 [42] H CF 3 91 [42] Me H 93 [42] (CH=CH) 2 99 [42] 2.9.2 Amination of C(sp 2 )-H Bonds…”

“…In the presence of an ortho-directing group, aryl C-H bonds can be successfully amidated intermolecularly with a range of azides, including sulfonyl (Scheme 20, Scheme 21, and Scheme 22), [37][38][39] aryl (Scheme 23), [40] alkyl (Scheme 24), [41] and acyl (Scheme 25) [42] azides catalyzed by either bis[dichloro(Å 5 -pentamethylcyclopentadienyl)rhodium(III)] [{Rh(Cp*)Cl 2 } 2 ] or bis[dichloro(Å 5 -pentamethylcyclopentadienyl)iridium(III)] [{Ir(Cp*)Cl 2 } 2 ] to give arylamines 66-71. The process is assisted by a number of directing groups and is tolerant of a range of aryl substitution in the substrate.…”

“…Conditions are also applicable to more weakly coordinating esters and ketones, with the addition of acetic acid and lithium carbonate to increase the coordinating efficiency of these substrates to give arylamines 68 (Scheme 22). [39] Notably, acyl azides are employed without observing the Curtius rearrangement, instead using the acyl azide as the nitrogen donor of an acyl amino group. Reported stoichiometric ratios of substrate to azide vary, depending upon the class of azide and substitution of the aryl ring.…”

“…Electron-donating and electron-withdrawing groups are tolerated at the R 1 position.Scheme 22Amidation of Arenes with Weak Directing Groups Using Sulfonyl Azides and Bis[dichloro(Å 5 -pentamethylcyclopentadienyl)iridium(III)][39] {Ir(Cp*)Cl 2 } 2 (4 mol%) AgNTf 2 (16 mol%) AcOH (15 mol%), Li 2 CO 3 (15 mol%) 1,2-dichloroethane, 50 o C, 12 h…”

Mild metal-catalyzed C–H activation: examples and concepts

“…127 The initial hypothesis presumed that the binding efficiency of weakly coordinating substrates toward a metal center could be improved in the presence of both base and acid additives. Although basic species are recognized to assist CMD C-H activation, they also coordinate strongly to the metal catalyst and can consequently outcompete substrate binding when weakly coordinating directing groups are employed.…”