Chemistry Reference
In-Depth Information
CO
2
H
CO
2
H
B(OH)
2
0.4 mol% [(
t
-Bu
3
P)Pd(
μ
-Br)]
2
+
N
N
Cs
2
CO
3
,H
2
O, 83 °C
88 % crude
N
N
F
Cl
60 g scale
F
Scheme 3.36
Scalable Suzuki-Miyaura cross-coupling using [(t-Bu
3
P)Pd(m-Br)]
2
.
Cl
P
Cl
P
Pd
Pd
Pd
C
l
Q-Phos
C
l
Q-Phos
Pd
Pd
Cl
P
NMe
2
Cl
P
NMe
2
Cl
P
Pd
Pd
Figure 3.19 LPd(p-allyl)Cl catalysts.
Researchers at Novartis reported a scalable process to make a PDE-4 in-
hibitor, incorporating a Pd-catalyzed Suzuki-Miyaura coupling as the final
step (Scheme 3.36).
111
In order to remove any remaining Pd residues from
the active pharmaceutical ingredient (API), the product was treated with the
metal scavenger (chelating anion exchanger) Smopex 110.
3.7.2 LPd(R-allyl)(Cl)
Inspired by the p-allyl-based NHC-containing Pd precatalysts developed by
Nolan and co-workers,
99
Colacot and co-workers recently reported another
P-based class of precatalysts generating catalytically active LPd(0).
112
These
LPd(R-allyl)(Cl) (L
¼
PR
3
) complexes are depicted in Figure 3.19. The
(dtbnp)Pd(allyl)Cl (dtbnp
¼
di-tert-butylneopentylphosphine) was initially
demonstrated as a highly active catalyst in amination and a-arylation re-
actions.
113
In some cases, amination reactions involving aryl bromides could
be carried out at room temperature under air. Aryl chlorides required ele-
vated temperatures under a nitrogen atmosphere.
The preformed catalyst provided results superior to those obtained using
the in situ-generated catalyst
from Pd
2
(dba)
3
and free dtbnp ligand
(Figure 3.20).
The preformed catalyst is stable when stored under air at low temperature.
This avoids handling of the pyrophoric free ligand. When stored at ambient
temperature, the complex slowly turns from yellow (good catalyst) to green
(decomposed).
Nolan and co-workers had previously observed significant effects on the
catalysis when the allyl ligand was changed to crotyl or cinnamyl.
99
Sub-
sequent to the initial success of (dtbnp)Pd(allyl)Cl, the role of the p-allyl
moiety of the catalyst and the effect of the nature of the tertiary phosphine
Search WWH ::
Custom Search