Chemistry Reference
In-Depth Information
S
Pd
2
(dba)
3
, P
t
-Bu
3
,
NaO
t
-Bu, K
2
CO
3
S
Br
H
H
2
N
Cl
Cl
2
.
5
1
2
2
.
5
1
3
Scheme 2.149
Pd(OAc)
2
, Davephos,
Cs
2
CO
3
F
3
C
CN
F
3
C
CN
+
Cl
H
2
N
Et
H
Et
2.515
2.514
O
O
F
3
C
1. H
3
O
+
2. CbzCl, LiO
1. NaBH
4
, MgCl
2
2. H
+
H
OBn
t
-Bu
H
Et
2.516
F
3
C
CF
3
CO
2
Me
HN
1. EtOCOCl, py
2.
CO
2
Me
-(F
3
C)
2
C
6
H
3
CH
2
Br,
KO
m
F
3
C
N
t
-Bu
F
3
C
H
Et
N
Et
2
5
2
.
1
8
CO
2
Et
Scheme 2.150
The coupling of 2-chloroaniline
2.520
with 2-bromostyrene
2.519
using the ligand Brettphos
1.22
showed
the expected selectivity for coupling at the bromo position (Scheme 2.151). The product could be converted
to three different heterocyclic systems by palladium catalysis according to the ligand employed.
183
Use of
Davephos
1.20
as the ligand resulted in formation of the benzodiazepine
2.522
by an apparent
endo
-Heck
reaction, while use of tri(
t
-butyl)phosphine
1.10
gave the acridine
2.523
via an
exo
-Heck reaction. In contrast,
using Trixiephos
1.13
, the vinyl group was ignored and the carbazole
2.524
was produced by C-H activation.
A very wide range of nitrogen derivatives has been employed.
184
Common ones include amides
(Scheme 2.152),
185
sulfonamides, carbamates (Scheme 2.153), including cyclic carbamates (Scheme 2.154)
186
and ureas (Scheme 2.155).
187
Reactions may be not only intermolecular, but also intramolecular
(Scheme 2.156).
188
N
-Heterocycles may also be arylated.
189
A double coupling of methane sulfonamide
was used to prepare dofetilide
2.538
, an antiarrhythmic agent (Scheme 2.157).
190
Mesylates have also been
a substrate for coupling (Scheme 2.158).
191
As these
N
-acyl and
N
-sulfonyl derivatives tend to be more
acidic than simple amines, weaker bases tend to be employed. More exotic derivatives of nitrogen, including
sulfoximines (Scheme 2.159),
192
hydrazines (Scheme 2.160)
193
and guanidines
194
can also be coupled. The in-
tramolecular coupling of a
-lactam was employed in the synthesis of carbapenems
2.548
(Scheme 2.161).
195
An important objective has been the development of “ammonia surrogates”, molecules that can be coupled
to yield primary amines. One way is to use secondary amines bearing groups such as allyl (Scheme 2.162)
