Abbreviations
mW
Microwave
Cy
Cyclohexyl
Dba
Dibenzylideneacetone
Dppe
1,2-Bis(diphenylphosphinoethane)
Dppp
1,3-Bis(diphenylphosphinopropane)
Hex
n-Hexyl
HMDS Hexamethyldisilazide
IPr
N,N
0 -Bis(2,6-diisopropylphenyl)imadalol-2-ylidene
i-Pr
Isopropyl
PMP
4-Methoxyphenyl
SAR
Structure–activity relationship
TBS
tert-Butyldimethylsilyl
1 Introduction and Scope
Molecules that contain aryl C–N bonds play important roles in many different areas of
chemistry, including materials and pharmaceuticals. For example, a number of topselling drugs, including Lipitor [1], Abilify [2], and Celebrex [3], contain this functional unit. Over the past 15 years, Pd-catalyzed coupling reactions between aryl
halides and amines have developed into broadly utilized methods for sp
2 C–N bond
formation. These transformations have been used on both small academic scales and
very large industrial scales. Due to the significance of this field, a number of reviews
have been previously published describing various stages of its development ([4–11];
for a comprehensive review on the Buchwald biaryl phosphine ligands, see [12]; for a
review on the utility of Josiphos-type ligands in Pd-catalyzed N-arylation reactions,
see [13]; [14–21]). This review outlines key aspects of Pd-catalyzed sp
2 C–N bond
forming cross-coupling reactions of nitrogen nucleophiles and aryl/alkenyl halides and
pseudohalides that were reported in the literature between 2004 and 2008. Although
this review is focused primarily on synthetic aspects of the chemistry, a very brief
description of reaction mechanism along with a brief historical background is provided
to place the current work in context and aid the reader.
2 Early Work Prior to 2004
The first example of the formation of an aryl C–N bond via a Pd-catalyzed crosscoupling reaction of an aryl halide was reported in 1983 by Migita and coworkers
[22, 23]. During the course of their studies on the reactivity of organotin compounds,
2
G.S. Lemen and J.P. Wolfe
mW
Microwave
Cy
Cyclohexyl
Dba
Dibenzylideneacetone
Dppe
1,2-Bis(diphenylphosphinoethane)
Dppp
1,3-Bis(diphenylphosphinopropane)
Hex
n-Hexyl
HMDS Hexamethyldisilazide
IPr
N,N
0 -Bis(2,6-diisopropylphenyl)imadalol-2-ylidene
i-Pr
Isopropyl
PMP
4-Methoxyphenyl
SAR
Structure–activity relationship
TBS
tert-Butyldimethylsilyl
1 Introduction and Scope
Molecules that contain aryl C–N bonds play important roles in many different areas of
chemistry, including materials and pharmaceuticals. For example, a number of topselling drugs, including Lipitor [1], Abilify [2], and Celebrex [3], contain this functional unit. Over the past 15 years, Pd-catalyzed coupling reactions between aryl
halides and amines have developed into broadly utilized methods for sp
2 C–N bond
formation. These transformations have been used on both small academic scales and
very large industrial scales. Due to the significance of this field, a number of reviews
have been previously published describing various stages of its development ([4–11];
for a comprehensive review on the Buchwald biaryl phosphine ligands, see [12]; for a
review on the utility of Josiphos-type ligands in Pd-catalyzed N-arylation reactions,
see [13]; [14–21]). This review outlines key aspects of Pd-catalyzed sp
2 C–N bond
forming cross-coupling reactions of nitrogen nucleophiles and aryl/alkenyl halides and
pseudohalides that were reported in the literature between 2004 and 2008. Although
this review is focused primarily on synthetic aspects of the chemistry, a very brief
description of reaction mechanism along with a brief historical background is provided
to place the current work in context and aid the reader.
2 Early Work Prior to 2004
The first example of the formation of an aryl C–N bond via a Pd-catalyzed crosscoupling reaction of an aryl halide was reported in 1983 by Migita and coworkers
[22, 23]. During the course of their studies on the reactivity of organotin compounds,
2
G.S. Lemen and J.P. Wolfe