Palladium-Catalyzed Chemoselective Decarboxylative Ortho Acylation of Benzoic Acids with α-Oxocarboxylic Acids

Abstract

Palladium-catalyzed chemoselective decarboxylative cross coupling of benzoic acids with α-oxocarboxylic acids was realized via an arene sp(2) C-H functionalization process. This work represents the first example of transition-metal-catalyzed cross-coupling reactions with two acids acting in different roles. The synthetic utility of this method was confirmed by the synthesis of pitofenone, an antispasmodic used in the combined drug Spasmalgon.

The use of carboxylic acids as traceless directing groups for regioselective C–H bond functionalisation

“…30 Furthermore, they also revealed that, upon changing the reaction conditions, they could effect a carbonylation or hydroxylation sequence, followed by protodecarboxylation. The functionalisation conditions used were originally developed by the groups of Larrosa, 31 Ge, 32 and Yu 33 for the ortho-arylation, carbonylation and hydroxylation of benzoic acids respectively. The novelty of this report by Zhang is the removal of the directing group after the functionalisation to provide a range of para-substituted arenes in good to excellent overall yields.…”

Palladium-Catalyzed Environmentally Benign Acylation

“…Hz, CH 3 ) ppm. 13 , 2921, 2851, 1720, 1671, 1603, 1463, 1279, 1139, 1084, 1015, 935, 899, 857, 751, 710 cm -1 .. 1 =2981, 2851, 1715, 1669, 1604, 1351, 1311, 1278, 1106, 1079, 932, 714 cm -1 . 1 H NMR (CDCl 3 , 400 MHz): δ=8.04 (dd, 1H, J=7.8 and J=0.9 Hz), 7.65 (d,2H,J=8.3 Hz),7.58 (td,1H,J=7.3 and J=1.4 Hz), 7.57-7.51 (m, 1H) 7.33 (dd, 1H, J=7.5 and J=1.2 Hz), 7.20 (d,2H,J=8.3 Hz),4.97 (sep,1H,J=6.3 Hz), 2.38 (s, 3H), 1.01 (d,6H,J=6.3 Hz), ppm.…”

“…Notably, the present protocol proved to be efficient as it enables the synthesis of pitofenone 10ap in just two steps (Scheme 1). 13 nature of Ag + ions, it might be reasonable to form AgI while combining B with A. On the other hand, acceleration of the reaction in the presence of Ag 2 O might also be due to salt effect on [Pd]-catalysis.…”

Carboxylic Acids as Directing Groups for C−H Bond Functionalization

“…A Rh I –Rh III catalytic cycle is thought to first proceed through oxidative Rh insertion at the acyl−O bond of the anhydride, followed by intramolecular insertion of Rh at the proximal C−H bond and reductive elimination to yield ortho ‐acylbenzoates. In 2013, the ortho ‐acylation of benzoic acids was also achieved by Mao and Ge by using α‐oxocarboxylic acids and Pd(TFA) 2 as catalyst …”