Picolinamides as Effective Ligands for Copper‐Catalysed Aryl Ether Formation: Structure–Activity Relationships, Substrate Scope and Mechanistic Investigations

Abstract

The use of picolinic acid amide derivatives as an effective family of bidentate ligands for copper-catalysed aryl ether synthesis is reported. A fluorine-substituted ligand gave good results in the synthesis of a wide range of aryl ethers. Even bulky phenols, known to be very challenging substrates, were shown to react with aryl iodides with excellent yields using these ligands. At the end of the reaction, the first examples of end-of-life Cu species were isolated and identified as Cu(II) complexes with several of the anionic ligands tested. A preliminary mechanistic investigation is reported that suggests that the substituents on the ligands might have a crucial role in determining the redox properties of the metal centre and, consequently, its efficacy in the coupling process. An understanding of these effects is important for the development of new efficient and tunable ligands for copper-based chemistry.

Green alternative solvents for the copper-catalysed arylation of phenols and amides

“…In our previous investigation we observed that the catalytic activity increased using ligands bearing electron-withdrawing substituents on the phenyl ring. 43 Similar observations can be made for the results in Figure 1. Ligands L3 or L4, substituted with electronwithdrawing groups are generally more effective than L2 and L1.…”

“…This is true using either base, but the Scheme 2: Substrate scope: isolated yields in i-PrOAc (bold) and MeCN (italics, from ref. [ 43]); X = I, if not otherwise specified difference between the ligands is accentuated using K3PO4 (Figure 1b). In this case, ligand L1 is always considerably less effective than the others, whilst using Cs2CO3 its efficacy is sometimes only a little inferior ( Figure 1a).…”

“…No competing arylation of the amino group was observed in these cases. Compound 23 was obtained in 17% yield, while arylation of 8-hydroxyquinaldine (24) occurred in 21% yield (in MeCN: 4% and 37% respectively 43 ). Aryl bromides were also tested in the reaction: reaction with 4-bromoanisole resulted in max 40% yield, considerably lower than the corresponding iodide (compounds 1, 4, 7, 10, 21).…”

“…42 Herein we report the first investigation on the use of alkyl acetates and other green organic solvents in the copper catalysed arylation of phenols and amides, in combination with picolinamide ligands, which proved effective for the C-O coupling in acetonitrile. 43 …”

Structural studies of titanium(IV) picolinamide alkoxide and oxide derivatives

“…[17][18][19] We have also reported the uses of aluminium picolinamides for the ring-opening polymerisation of rac-lactide for use in the preparation of coloured polymeric materials 20 and picolinamide ligands as effective ligands for copper-catalysed aryl ether formation. 21 Herein, we report the reactions of picolinamide ligands with titanium(IV) precursors and discuss the structural properties of the potential intermediates. The reactions give titanium complexes with the ligand bound as either the amide or iminolate, in which the ligand is exclusively bound N,O.…”