An Improved Cu-Based Catalyst System for the Reactions of Alcohols with Aryl Halides

Abstract

The use of 3,4,7,8-tetramethyl-1,10-phenanthroline (Me(4)Phen) as a ligand improves the Cu-catalyzed cross-coupling reactions of aryl iodides and bromides with primary and secondary aliphatic, benzylic, allylic, and propargylic alcohols. Most importantly, by employing this catalyst system, the need to use an excessive quantity of the alcohol coupling partner is alleviated. The relatively mild conditions, short reaction times, and moderately low catalyst loading allow for a wide array of functional groups to be tolerated on both the electrophilic and nucleophilic coupling partners.

Use of Acylhydrazine‐ and Acylhydrazone‐Type Ligands to Promote CuI‐Catalyzed C–N Cross‐Coupling Reactions of Aryl Bromides with N‐Heterocycles

“…The CuI/L2 catalytic system is also applicable to the Ullmann coupling reactions of other N-heterocycles with 4-bromoacetophenone and 2-bromopyridine (Entries [11][12][13][14][15][16][17]. The heterocycles, such as pyrrole (Entry 11), pyrazole (Entries 12 and 15), triazole (Entries 13 and 16), and benzimidazole (Entries 14 and 17) were found to be effective nucleophilic counterparts for the coupling process, and the respective N-arylated products were obtained in good to excellent yields.…”

“…[7][8][9] Among them, the copper-catalyzed Ullmann-type coupling reactions are particularly attractive, because they often allow the use of low-cost starting materials and readily available copper complexes. [8][9][10][11][12][13][14][15][16] However, the initial protocols required harsh conditions, such as high temperatures, stoichiometric amounts of the copper reagents, and strong alkoxide bases. [17] Recent advances revealed that a judicious combination of certain ligands and copper reagents enables the reaction to be efficiently performed under milder conditions.…”

“…It has been generally thought that ligands increase the solubility of copper salts and prevent their aggregation in the reaction process, while the ligands also enhance the reactivity by increasing the electronic density on the catalytic species. [11][12][13][14][15][16] [ activity of Ullmann reactions was assessed by using a combination of these ligands with CuI. The catalytic system is very efficient for the C-N coupling reaction of azoles with aryl and heteroaryl bromides.…”

“…Various types of ligands have been introduced to promote copper-catalyzed Ullmann-type N-arylation reactions. [10][11][12][13][14][15][16] Most notable ligands are bidentate N,O, [11][12][13] N,N, [14,15] or O,O [16] compounds. The high catalytic activity attained in these systems can most likely be ascribed to the formation of chelating Cu I species.…”

“…For example, Buchwald and co-workers have revealed that the activity and selectivity of various Cu-catalyzed Ullmann reactions can be controlled by changing the type, number, and position of substituents in the phenanthroline backbone. [14] Although many ligands have been reported, [9][10][11][12][13][14] the rapid assembly and flexible modification of structurally diverse ligand systems by simple synthetic methods are still important for the development of effective catalysts for the widespread applications of coupling reactions.…”