Palladium-Catalyzed Decarboxylative ortho-Acylation of Anilines with Carbamate as a Removable Directing Group

Abstract

An efficient palladium-catalyzed decarboxylative ortho-acylation of anilines with α-oxocarboxylic acids has been realized by using carbamate as a directing group (DG). The reaction proceeds smoothly with high regioselectivity to afford diverse acylation products of aniline derivatives in moderate to good yields under mild conditions. This transformation exhibits broad substrate scope and highly functional group tolerance. In addition, the employed DG can be easily removed to give the corresponding 2-amino aromatic ketones. Importantly, several transformations of the synthesized ortho-acylated anilines into several synthetically valuable products have been demonstrated for their utilities.

Pd‐Catalyzed Decarboxylative Ortho‐Aroylation of 2‐Aryl‐quinazolinone Comprising Intrinsic Directing Group with α‐Oxocarboxylic Acids

“…Based on the results of these experiments with support of literature, [5–13] plausible reaction mechanism involving cyclopalladation/radical intermediate has been proposed (Scheme 5). Pd(OAc) 2 may be transformed to Pd(TFA) 2 .…”

“…Based on the results of these experiments with support of literature, [5][6][7][8][9][10][11][12][13] plausible reaction mechanism involving cyclopalladation/radical intermediate has been proposed (Scheme 5). In conclusion, we have proposed a palladium catalyzed decarboxylative aroylation of 2-aryl-quinazolinone with oxocarboxylic acids to generate diaryl ketones.…”

“…[3] Ge et al reported decarboxylative acylation of acetanilides and 2-phenylpyridines with α-oxocarboxylic acids (1) via Pd-catalyzed directing group assisted CÀ H activation. [4] Consequent of these initial work, differentdirecting groups such as benzamide, [5] carbamates, [6] Ophenyl carbamates, [7] O-methyl ketoximes, [8] azobenzenes, [9] azoxybenzenes, [10] N-nitroso, [11] N-sulfoximine [12] and some other [13] have been successfully applied for directing group assisted decarboxylative CÀ H acylation (Scheme 1a). In most of the reports, directing groups either needs to be pre-built-in and so disconnected afterward.…”

α-Keto Acids: Acylating Agents in Organic Synthesis

“…Intermediate III undergoes then a reductive elimination to give the product 51or and Pd(0), which is reoxidized to Pd(II) by (NH 4 ) 2 S 2 O 8 (Scheme 73). 146 Recently, Wang and co-workers 147 have disclosed the Pd(II)-catalyzed decarboxylative ortho-acylation of C−H sp 2 bonds using carbamates 99 as a removable directing group and α-keto acids 1 as acylating agents. This approach involves the stirring of a mixture of 99 and aryl-substituted glyoxylic acid 1 (1.8 equiv) in the presence of Pd(OAc) 2 (10 mol %) as the catalyst, (NH 4 ) 2 S 2 O 8 (2 equiv) as the oxidant, and p-toluenesulfonic acid (PTSA, 0.75 equiv) as an additive in DCE as the solvent at 45 °C for 24 h. Under these conditions, a diversity of 36 ortho-acylated aniline carbamates 51 were obtained in poor to very good yields.…”

Pd(II)-Catalyzed C-H Acylation of (Hetero)arenes—Recent Advances

“…A bimetallic palladium 6-membered cyclopalladated complex could be obtained and used as catalyst for this reaction. Recently, carbamates have also been used as directing groups for the acylation with α-oxoacids 8 ( Scheme 9 b) obtaining 32 in moderate to good yields [ 35 ]. Carbamate directing group could be easily removed obtaining amine 33 that could be derivatized to various heterocyclic systems, such as quinazoline or phenylquinoline.…”