3 C–N Bond Formation from Arylboronic Acids and Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . 191
4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
1 Introduction and Scope of the Chapter
For more than a century copper-mediated coupling reactions of aryl halides with
amines [1, 2], and phenols [3, 4], (Ullmann condensations), amides and carbamates
[5, 6], (Ullmann–Goldberg condensations) or activated methylene compounds [7]
(Ullmann–Hurtley condensations) have been three of the most useful and practical
methods for the formation of C(aryl)–N, C(aryl)–O and C(aryl)–C bonds [8–16].
Despite its usefulness in life sciences and materials industries, Ullmann-type
coupling reactions have not been employed to its full potential for a long time until
2000 due to the harsh reaction conditions, restricted range of substrates and the
moderate yields obtained. The synthetic scope of these transformations was often
limited because of the high temperatures needed (>200
C) and of the concomitant
use of high-boiling-point polar solvents. Another drawback was the use of stoichiometric amounts of copper reagents and of aryl halides activated or substituted by
o-carboxylic groups [17–27].
However, some studies amongst the literature had shown rate enhancements when
arylations were performed in the presence of copper ligands, additives, or substrates
bearing chelating groups [28–35]. These latter compounds were supposed to improve
the catalyst solubility and stability or to prevent the aggregation of the metal. Finally,
a renaissance of Ullmann-coupling reactions has been initiated in 2001 by two
academic groups [36–40], with the discovery of the first both versatile and very
efficient new copper/ligand systems for C–C, C–N, or C–O coupling which enabled
the use of only catalytic amounts of metal under milder temperature conditions. Since
these important breakthroughs based on a unique system for all type of coupling, a
bountiful number of methods have been described with an extraordinary tolerance of
functional groups. Nowadays, revisited copper-catalyzed cross-coupling reactions of
aryl halides with nucleophiles are competitive, particularly for aryl iodides and
bromides, to the expensive and more toxic palladium-catalyzed procedures.
This chapter covers the C(aryl)–N bond formation via copper-catalyzed
coupling of nitrogen nucleophiles (N-heterocycles, amines, anilines, amides,
ammonia, azides, hydroxylamines, nitrite salts, phosphonic amides) with aryl
halides. The C(aryl)–N bond formation as a result of the coupling between these
nucleophiles and arylboronic acids (the Chan–Lam reaction) will be presented, too.
Amongst the bountiful amount of publications related to this topic for about
10 years, this chapter mainly focuses on the most significant results and important
breakthroughs. Its scope is to highlight the most efficient homogeneous catalytic
system based on the association of a copper source with an original ligand,
174
F. Monnier and M. Taillefer
4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
1 Introduction and Scope of the Chapter
For more than a century copper-mediated coupling reactions of aryl halides with
amines [1, 2], and phenols [3, 4], (Ullmann condensations), amides and carbamates
[5, 6], (Ullmann–Goldberg condensations) or activated methylene compounds [7]
(Ullmann–Hurtley condensations) have been three of the most useful and practical
methods for the formation of C(aryl)–N, C(aryl)–O and C(aryl)–C bonds [8–16].
Despite its usefulness in life sciences and materials industries, Ullmann-type
coupling reactions have not been employed to its full potential for a long time until
2000 due to the harsh reaction conditions, restricted range of substrates and the
moderate yields obtained. The synthetic scope of these transformations was often
limited because of the high temperatures needed (>200
C) and of the concomitant
use of high-boiling-point polar solvents. Another drawback was the use of stoichiometric amounts of copper reagents and of aryl halides activated or substituted by
o-carboxylic groups [17–27].
However, some studies amongst the literature had shown rate enhancements when
arylations were performed in the presence of copper ligands, additives, or substrates
bearing chelating groups [28–35]. These latter compounds were supposed to improve
the catalyst solubility and stability or to prevent the aggregation of the metal. Finally,
a renaissance of Ullmann-coupling reactions has been initiated in 2001 by two
academic groups [36–40], with the discovery of the first both versatile and very
efficient new copper/ligand systems for C–C, C–N, or C–O coupling which enabled
the use of only catalytic amounts of metal under milder temperature conditions. Since
these important breakthroughs based on a unique system for all type of coupling, a
bountiful number of methods have been described with an extraordinary tolerance of
functional groups. Nowadays, revisited copper-catalyzed cross-coupling reactions of
aryl halides with nucleophiles are competitive, particularly for aryl iodides and
bromides, to the expensive and more toxic palladium-catalyzed procedures.
This chapter covers the C(aryl)–N bond formation via copper-catalyzed
coupling of nitrogen nucleophiles (N-heterocycles, amines, anilines, amides,
ammonia, azides, hydroxylamines, nitrite salts, phosphonic amides) with aryl
halides. The C(aryl)–N bond formation as a result of the coupling between these
nucleophiles and arylboronic acids (the Chan–Lam reaction) will be presented, too.
Amongst the bountiful amount of publications related to this topic for about
10 years, this chapter mainly focuses on the most significant results and important
breakthroughs. Its scope is to highlight the most efficient homogeneous catalytic
system based on the association of a copper source with an original ligand,
174
F. Monnier and M. Taillefer