Chemistry Reference
In-Depth Information
P(
t
Bu)
2
Me
2
N
L3
R
O
R
Pd
2
(dba)
3
(1.5 mol%)
L3
Cl
N
(5.0 mol%)
NaO
t
Bu or Cs
2
CO
3
1,4-dioxane, 4Å MS
85-120
o
C
Also prepared: dibenzooxazepines (6 examples, 69-94 %)
dibenzodiazepinones (5 examples, 73-93 %)
dibenzooxazepinone (82 %)
N
+ NH
3
(5 -7 equiv.)
R
2
R
1
R
1
R
2
H
dibenzodiazepines
9 examples
43-93 %
Figure 5.5 Application of ammonia monoarylation in the synthesis of dibenzodia-
zepines and related structural analogs.
can be conducted in air. It is worthy of mention that this ammonia mono-
arylation chemistry involving 2-halo(hetero)arylacetylenes does not exhibit
the substrate scope limitations encountered when using Pd(cinnamyl)Cl]
2
/
L1 (Figure 5.3),
35
in that 2-chloro(hetero)arylacetylenes and substrates
featuring sp
3
substituents at the alkynyl terminus were successfully trans-
formed in the presence of [Pd(cinnamyl)Cl]
2
/L2 catalyst mixtures.
36
Biarylmonophosphine ligands developed by Buchwald and co-workers
have played a central role in the advancement of BHA chemistry,
10,14
and
their application in the selective monoarylation of ammonia has been
examined.
37-39
In preliminary experiments probing the cross-coupling of
ammonia (5 equiv.) with chlorobenzene, a selection of biarylmonophos-
phine ligands (5 mol%) in combination with Pd
2
(dba)
3
(2 mol% Pd) as
the palladium source (dba
¼
dibenzylideneacetone; 80 1C) were tested; the
ligand tBuDavePhos (L3) was found to exhibit the best performance among
the ligands examined in terms of substrate conversion and monoarylation
selectivity.
37
This Pd
2
(dba)
3
/L3 precatalyst system was subsequently em-
ployed with success by Tsvelikhovsky and Buchwald
38
in BHA reactions
employing ammonia, whereby the derived aniline intermediate undergoes
an intramolecular condensation reaction to afford dibenzodiazepines and
related biologically active structural analogs (Figure 5.5). The propensity of
biarylmonophosphine ligands including L3
40
to bind Pd(0) or Pd(II) via
phosphorus and one or more carbon atoms of the lower flanking arene ring
has been established.
10
In this context, the specific involvement of the
presumably uncoordinated dimethylamino group in L3 in promoting am-
monia monoarylation selectivity remains unclear.
5.2.3 Application of Buchwald Palladacycles and
Imidazolemonophosphines
The application of aminobiphenyl palladacyclic precatalysts featuring bulky
biarylmonophosphine ligands in the selective monoarylation of ammonia
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