Biaryl and Aryl Ketone Synthesis via Pd‐Catalyzed Decarboxylative Coupling of Carboxylate Salts with Aryl Triflates

Abstract

A bimetallic catalyst system has been developed that for the first time allows the decarboxylative cross-coupling of aryl and acyl carboxylates with aryl triflates. In contrast to aryl halides, these electrophiles give rise to non-coordinating anions as byproducts, which do not interfere with the decarboxylation step that leads to the generation of the carbon nucleophilic cross-coupling partner. As a result, the scope of carboxylate substrates usable in this transformation was extended from ortho-substituted or otherwise activated derivatives to a broad range of ortho-, meta-, and para-substituted aromatic carboxylates. Two alternative protocols have been optimized, one involving heating the substrates in the presence of Cu(I)/1,10-phenanthroline (10-15 mol %) and PdI(2)/phosphine (2-3 mol %) in NMP for 1-24 h, the other involving Cu(I)/1,10-phenanthroline (6-15 mol %) and PdBr(2)/Tol-BINAP (2 mol %) in NMP using microwave heating for 5-10 min. While most products are accessible using standard heating, the use of microwave irradiation was found to be beneficial especially for the conversion of non-activated carboxylates with functionalized aryl triflates. The synthetic utility of the transformation is demonstrated with 48 examples showing the scope and limitations of both protocols. In mechanistic studies, the special role of microwave irradiation is elucidated, and further perspectives of decarboxylative cross-couplings are discussed.

Methyl 2‐Furoate: An Alternative Reagent to Furan for Palladium‐Catalysed Direct Arylation

“…However, they obtained only 41 % yield for the coupling of 2‐furoic acid with bromobenzene. A similar result was obtained by Goossen in the presence of 4‐bromotoluene (yields 38–75 %) 10b,10c…”

Low‐Temperature Ag/Pd‐Catalyzed Decarboxylative Cross‐Coupling of Aryl Triflates with Aromatic Carboxylate Salts

“…Phenanthroline, which was the most effective ligand for copper, hampered the activity of silver. Better results were obtained with pyridine-type ligands, and near-quantitative yields were achieved with the sterically encumbered 2,6-lutidine (20 mol %) ( [13] Under these optimized conditions (5 mol % Ag 2 CO 3 , 3 mol % PdCl 2 , 9 mol % PPh 3 , 20 mol % 2,6-lutidine, 130 8C), we investigated the scope of the new protocol with regard to the potassium carboxylate in its coupling with 4-chlorophenyl triflate (2 a) ( Table 2). …”

“…[11] Larrosa et al independently discovered a similar protocol. [12] In addition, we were able to show that decarboxylative cross-couplings can be performed using aryl electrophiles with non-coordinating leaving groups such as triflates [13] or tosylates. [14] We reasoned that the low affinity of these ions to silver(I) might enable the crucial salt metathesis between silver sulfonate salts a and potassium carboxylates 1 (Scheme 1).…”

“…The use of sterically demanding ligands such as PA C H T U N G T R E N N U N G (o-Tol) 3 had an adverse effect on the decarboxylation step (Table 1, entries 6-11). Among the silver sources tested, silver carbonate gave the best results, but other silver salts may be used as well (Table 1, entries [12][13][14]. The reaction works best in aprotic solvents such as Nmethylpyrrolidone (NMP) or dimethylacetamide (DMAc).…”

The Aromatic Carbon–Carbon ipso‐Substitution Reaction

“…In the latter case, the carboxylic acid is a valid substitute for sensitive and costly organometallic reagents (organoboron, -tin, -zinc, -copper, -silicon, or -magnesium) that are usually employed for this purpose. [3] Most of the merit can be attributed to the group of Goossen, [77][78][79][80][81][82][83][84][85] which has introduced an advantageous decarboxylative cross-coupling methodology in which a carboxylic acid or its alkaline salt were converted into carbon nucleophiles by extrusion of CO 2 followed by coupling with haloarenes (ArÀX; X = I, Br, or Cl) or aryl triflates as electrophilic substrates. The original Pd-mediated decarboxylative cross-coupling reaction was accomplished by using stoichiometric amounts of a copper catalyst.…”