types of catalysts have not yet found widespread appeal or applications and are
therefore not covered in detail.
3.1.1 Bidentate Phosphines
The efficacy of dppf, BINAP, Josiphos, and other chelating ligands in Pd-catalyzed
N-arylation has prompted further exploration of bidentate ligands. An interesting
trans-chelating ligand 1 was recently prepared for N-arylation reactions of benzophenone imine [68]. For example, the selective cross-coupling of 4-bromoaniline with
benzophenone imine was achieved in 87% yield using a catalyst composed of 1/Pd
(OAc) 2 (Eq. 4). Competing oligomerization of the 4-bromoaniline was not observed.
Direct comparison of ligand 1 with other chelating phosphines suggests this ligand is
more efficient than dppf or BINAP for benzophenone imine N-arylation reactions, but
is of comparable reactivity to Xantphos when Pd 2 (dba) 3 is used as the precatalyst.
Br
H 2 N
Ph
Ph
NH
Pd(OAc) 2 (1.5 mol %)
1 (1.5 mol %)
+
H 2 N
N
Ph
Ph
87%
(i-Pr) 2 P
(i-Pr) 2 P
1
NaOt Bu, toluene
100 ºC
ð4Þ
The Hartwig group has continued to examine the reactivity of catalysts
supported by the Josiphos ligands [13, 69]. The use of 2 has allowed for the
coupling of highly functionalized aryl chlorides with primary amines and benzophenone imine. Amides, enolizable ketones, phenols, alcohols, and carboxylic acids
are tolerated in these reactions. For example, a catalyst composed of Pd(OAc) 2 /
2 effected the coupling of 4-chlorobenzoic acid with sec-butylamine in 85% yield
(Eq. 5). In addition, catalysts supported by this ligand are relatively long-lived, and
catalyst loadings as low as 0.001 mol% Pd can be employed in some instances.
This ligand is also effective for the N-arylation of aryl and heteroaryl tosylates at rt
[70]. Hartwig has also developed an air- and moisture-stable L 1 PdCl 2 -complex of
2 that serves as a user-friendly precatalyst [71]. This complex exhibits similar
reactivity to mixtures of Pd(OAc) 2 /2.
Cl
HO 2 C
+
H 2 N
H
N
HO 2 C
Pd(OAc) 2 (0.05 mol %)
2 (0.05 mol %)
85%
Fe
PCy 2
P(t-Bu) 2
2
LiHMDS, DME
100 ºC
ð5Þ
Palladium-Catalyzed sp
2 C–N Bond Forming Reactions. . .
7
therefore not covered in detail.
3.1.1 Bidentate Phosphines
The efficacy of dppf, BINAP, Josiphos, and other chelating ligands in Pd-catalyzed
N-arylation has prompted further exploration of bidentate ligands. An interesting
trans-chelating ligand 1 was recently prepared for N-arylation reactions of benzophenone imine [68]. For example, the selective cross-coupling of 4-bromoaniline with
benzophenone imine was achieved in 87% yield using a catalyst composed of 1/Pd
(OAc) 2 (Eq. 4). Competing oligomerization of the 4-bromoaniline was not observed.
Direct comparison of ligand 1 with other chelating phosphines suggests this ligand is
more efficient than dppf or BINAP for benzophenone imine N-arylation reactions, but
is of comparable reactivity to Xantphos when Pd 2 (dba) 3 is used as the precatalyst.
Br
H 2 N
Ph
Ph
NH
Pd(OAc) 2 (1.5 mol %)
1 (1.5 mol %)
+
H 2 N
N
Ph
Ph
87%
(i-Pr) 2 P
(i-Pr) 2 P
1
NaOt Bu, toluene
100 ºC
ð4Þ
The Hartwig group has continued to examine the reactivity of catalysts
supported by the Josiphos ligands [13, 69]. The use of 2 has allowed for the
coupling of highly functionalized aryl chlorides with primary amines and benzophenone imine. Amides, enolizable ketones, phenols, alcohols, and carboxylic acids
are tolerated in these reactions. For example, a catalyst composed of Pd(OAc) 2 /
2 effected the coupling of 4-chlorobenzoic acid with sec-butylamine in 85% yield
(Eq. 5). In addition, catalysts supported by this ligand are relatively long-lived, and
catalyst loadings as low as 0.001 mol% Pd can be employed in some instances.
This ligand is also effective for the N-arylation of aryl and heteroaryl tosylates at rt
[70]. Hartwig has also developed an air- and moisture-stable L 1 PdCl 2 -complex of
2 that serves as a user-friendly precatalyst [71]. This complex exhibits similar
reactivity to mixtures of Pd(OAc) 2 /2.
Cl
HO 2 C
+
H 2 N
H
N
HO 2 C
Pd(OAc) 2 (0.05 mol %)
2 (0.05 mol %)
85%
Fe
PCy 2
P(t-Bu) 2
2
LiHMDS, DME
100 ºC
ð5Þ
Palladium-Catalyzed sp
2 C–N Bond Forming Reactions. . .
7