Cu-Catalyzed Arylation of Bromo-Difluoro-Acetamides by Aryl Boronic Acids, Aryl Trialkoxysilanes and Dimethyl-Aryl-Sulfonium Salts: New Entries to Aromatic Amides

Abstract

We describe a mechanism-guided discovery of a synthetic methodology that enables the preparation of aromatic amides from 2-bromo-2,2-difluoroacetamides utilizing a copper-catalyzed direct arylation. Readily available and structurally simple aryl precursors such as aryl boronic acids, aryl trialkoxysilanes and dimethyl-aryl-sulfonium salts were used as the source for the aryl substituents. The scope of the reactions was tested, and the reactions were insensitive to the electronic nature of the aryl groups, as both electron-rich and electron-deficient aryls were successfully introduced. A wide range of 2-bromo-2,2-difluoroacetamides as either aliphatic or aromatic secondary or tertiary amides were also reactive under the developed conditions. The described synthetic protocols displayed excellent efficiency and were successfully utilized for the expeditious preparation of diverse aromatic amides in good-to-excellent yields. The reactions were scaled up to gram quantities.

Mechanochemical Ni‐Catalysed Arylation of ortho‐Hydroxyarylenaminones: Synthesis of Isoflavones

“…-/24 h model ortho-hydroxyarylenaminone by corresponding aryl bromide and thus the formation of the desired model isoflavone 4 a (Table 1, Entries 13,16,17). We identified the nitrogen-containing ligands (Scheme S5, L1, L2) which visibly contributed to the efficiency of this synthetic protocol.…”

“…Unexpectedly, when we switched our attention to cucurbit[n]urils [16] supramolecular entities capable to encapsulate small molecules, we observed an increase of the overall yields (Table 1, Entries 25-31). In the case of other supramolecular compounds [17] like calix [4]arene (L8) calix [5]arene (L9) the title reaction experienced a failure. The best outcome for the direct Ni-catalysed arylation of the model ortho-hydroxyarylenaminone by corresponding bromo compound was seen when we took ortho-hydroxyarylenaminone (1.0 mmol, 1.0 equiv.…”

Mechanochemical Defluorinative Arylation of Trifluoroacetamides: An Entry to Aromatic Amides

“…Carbamoylation reactions employing trihaloacetamides − as carbamoyl surrogates, via loss of CX 3 , have been scarcely studied. In particular, trifluoroacetamides are preferred over the other trihaloacetamides for their bench stability and preparation feasibility.…”

Mechanochemical arylative detrifluoromethylation of trifluoromethylarenes

“…In view of our expertise in fluorine chemistry, 32–35 herein we wish to report a mechanochemically enabled direct arylative detrifluoromethylation of trifluoromethylarenes. Our concept depicted in Scheme 1 proposes the in situ defluorinative conversion of ArCF 3 into ArCN (step A) and the subsequent decyanative arylation in a one-pot fashion (step B).…”

“…26 Since the Suzuki-Miyaura coupling is the most performed C-C bond formation reaction in both academia and industry, 27,28 expanding this powerful coupling reaction to efficiently involve benzonitrile remains highly sought after. [29][30][31] In view of our expertise in fluorine chemistry, [32][33][34][35] herein we wish to report a mechanochemically enabled direct aryla-tive detrifluoromethylation of trifluoromethylarenes. Our concept depicted in Scheme 1 proposes the in situ defluorinative conversion of ArCF 3 into ArCN (step A) and the subsequent decyanative arylation in a one-pot fashion (step B).…”