Ancillary Ligand Design in the Development of Palladium Catalysts for Challenging Selective Monoarylation Reactions - New Trends in Cross-Coupling: Theory and Applications - page 240

P(1-Ad) 2

N

O

L10

X NH 2

[Pd(cinnamyl)Cl] 2 (0.15-3.0 mol%)
L10 (0.30-6.0 mol%)

+

R NH 3

R

(3-4 equiv)

E E

NaO t Bu, 1,4-dioxane
25-110 o C

30 examples
52-98%

X = Cl, OTs
E = N, CH

Selected chemoselective aryl chloride amination examples:

NH 2

NH 2

N

NH 2

NH 2

NH 2

N

H 2 N

HN

98%
NH 3 > 2 o
acyclic aryl/alkyl

93%
NH 3 > 1 o aryl

97%
NH 3 > 2 o
cyclic dialkyl

61%
NH 3 > 1 o
branched alkyl

Selective monoarylation of ammonia employing the k 2 -P,N ligand Mor-
DalPhos (L10), including chemoselective reaction variants.

Figure 5.7

The proclivity of the [Pd(cinnamyl)Cl] 2 /L10 catalyst system for ammonia
monoarylation was exploited in unprecedented chemoselective aminations
involving aryl chloride substrates featuring potentially competitive NH
functionalities (Figure 5.7). 46 Reactions of aryl chlorides featuring secondary
aryl/alkyl-, diaryl- or dialkylamine addenda each afforded good to excellent
isolated yields (64-98%) of the ammonia-derived monoarylation product.
Perhaps even more remarkable was the ability of [Pd(cinnamyl)Cl] 2 /L10
to promote selectively the selective monoarylation of ammonia in the pres-
ence of aryl chlorides featuring contending primary aryl- or alkylamino
substituents.
In the same study, Stradiotto and co-workers briefly explored the co-
ordination chemistry of L10, including the synthesis of putative catalytic
intermediates; among the crystallographically characterized compounds
prepared was the chlorobenzene oxidative addition complex (k 2 -P,N-
L10)Pd(Ph)Cl (cf., B in Figure 5.1). 46 Remarkably, the use of rationally pre-
pared (k 2 -P,N-L10)Pd(Ph)Cl as a precatalyst enabled the first examples of
room temperature ammonia monoarylation employing (hetero)aryl
chlorides to be achieved. In a subsequent report, Stradiotto and co-workers
established broad scope for room temperature ammonia monoarylation
reactivity when using (k 2 -P,N-L10)Pd(Ph)Cl as a precatalyst (5 mol%),
including a range of (hetero)aryl (pseudo)halides (X ¼ Cl, Br, I, OTs) with
diverse substituents (alkyl, aryl, ether, thioether, ketone, amine, fluoro,
trifluoromethyl and nitrile), in addition to chemoselective monoarylations
(Figure 5.8). 47 Although a complete understanding of the properties of
(k 2 -P,N-L10)Pd(Ph)Cl that allow ecient room temperature ammonia
monoarylation with (hetero)aryl (pseudo)halides is currently lacking, it is