Chemistry Reference
In-Depth Information
Table 4.3
[Pd(IPr)(Et
3
N)Cl
2
] versus [Pd(IPr)(PEPPSI)] in the Suzuki reaction.
[Pd(IPr)(Et
3
N)Cl
2
](
14
)
or
[Pd(IPr)(PEPPSI)] (
15
)
(1mol%)
Cl
B(OH)
2
+
NaOH, EtOH
Yield (%)
a
Entry
[Pd(NHC)L
n
]
T (1C)
Time
1
[Pd(IPr)(PEPPSI)] (15)
25
3 h
37
2
[Pd(IPr)(Et
3
N)Cl
2
](14)
25
1.5 h
96
3
[Pd(IPr)(PEPPSI)] (15)
40
2 h
98
4
[Pd(IPr)(Et
3
N)Cl
2
](14)
40
20 min
98
a
By GC.
The IPr derivative proved highly active and versatile for various cross-coup-
ling reactions, including the Suzuki reaction. [Pd(IPr)(Im)Cl
2
] also promoted
the coupling in water.
50
4.3.1.1.5 Development of New NHC Ligands. The nature of the NHC lig-
and dictates the catalytic properties of the Pd-NHC catalyst. As a con-
sequence, modifying the nature of the NHC by modifying its steric demand
and also its electronic properties is important to achieve different kinds of
reactivities. Since 2010, many new NHCs have been developed for Suzuki-
Miyaura cross-coupling and we focus on some of the main advances here.
Lee and co-workers developed the amido-N-imidazolium salt 17 for the
formation of arylheterocycles at extremely low catalyst loadings.
51
The ligand
was found to be active with Pd loadings as low as 0.0001 mol%, yielding the
2-phenylpyridine with a turnover number (TON) of 850 000. The use of lig-
and 17 also allowed the preparation of two pharmaceutical compounds,
milrinone and irbesartan (Figure 4.11).
Kuriyama et al. also developed an in situ-generated system using ligand 18
for the preparation of polyheterocycles.
52
In this case, Cs
2
CO
3
was used as
the base for a greater group tolerance. Polyheterocycles were globally pre-
pared in good yields (Scheme 4.9).
The modification of the steric bulk of NHCs has also been widely studied
in recent years. Notably, Holland and co-workers studied the effect of in-
creased bulk at the para-position of the aryl groups of the NHC ligand.
53
Four new [Pd(NHC)(cin)Cl] complexes were prepared and their reactivities
were compared with that of the previously reported [Pd(IPr)(cin)Cl] com-
plex
54
(Figure 4.12, Table 4.4). All of the new complexes were found to be
more active for the coupling between 4-chloro(trifluoromethyl)benzene and
phenylboronic acid. This suggests that palladium catalysts bearing bulkier
ligands are more active, but this does not seem always to be the case. For
example, Straub and co-workers showed that [Pd(IPr**)(pyridinyl)Cl
2
](20,
Figure 4.12) was inactive in Suzuki coupling,
55
despite the fact that IPr** is
one of the largest known NHCs to date.
56
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