Ancillary Ligand Design in the Development of Palladium Catalysts for Challenging Selective Monoarylation Reactions - New Trends in Cross-Coupling: Theory and Applications - page 237

was examined further by Buchwald and co-workers in 2013. 39 While Brett-
Phos (L4) had been described in a previous publication by Fors and Buch-
wald as not being effective for ammonia monoarylation, 41 catalyst screening
studies confirmed the superiority of AdBrettPhos (L5), Me 3 (OMe)XPhos (L6),
Me 3 (OMe)PhXPhos (L7) and other structurally related and sterically de-
manding biarylmonophosphine ligands relative to L3 in the selective
monoarylation of ammonia with chlorobenzene using Pd 2 (dba) 3 as the
palladium source (3 equiv. NH 3 ; 2 mol% Pd; 5 mol% ligand). 39 Further
improvements in performance were achieved through the use of the ami-
nobiphenyl palladacyclic precatalyst complexes P1, P2 and P3 (featuring L5,
L6 and L7, respectively) (Figure 5.6). In particular, the use of P2/L6 (2 mol%
each) catalyst mixtures in place of Pd 2 (dba) 3 /L6 (1 and 4 mol%, respectively)
afforded faster rates of reaction and higher monoarylation product yields in
the cross-coupling of ammonia with (hetero)aryl halides. The P2/L6 catalyst
system proved useful in the selective monoarylation of ammonia employing
a broad selection of electron-rich, -neutral and -deficient aryl chlorides and
bromides (27 examples; 53-97%; Figure 5.6). However, for more sterically
hindered (hetero)aryl chlorides where the reactivity of P2/L6 was shown to
be lacking, the P3/L7 catalyst mixture featuring Me 3 (OMe)PhXPhos was
employed as a means of obtaining higher yields of the target (hetero)aniline
derivative. Reaction protocols employing P2/L6 or P3/L7 catalyst mixtures

(OMe)

Me

(Me)

OMe MeO Me

MeO P(1-Ad) 2 Me PR 2

i Pr i Pr i Pr i Pr

L6 , R = Cy

L5

L7

, R = Ph

i Pr i Pr

R

E

R

NH 2 >51 examples

36-99 %

X or Het X

or

P2 / L6 or P3 / L7 E

Het NH 2

palladacycle ( P1 - P3 , 2-5 mol%)
additional ligand ( L , 2-5 mol%)
NaO t Bu, 1,4-dioxane
25-110 °C

Pd NH 2

NH 3
(3 equiv)

MsO

X = Cl, Br
E = N, CH

L

P1: L L5

P2: L = L6
P3: L = L7

=

N

P1 / L5 or P3 / L7

R 1

8 examples
50-96 %

R
N

NH 2

(and related five-
membered electrophiles)

R 1

X

Figure 5.6 Expanding the scope of ammonia monoarylation by use of biaryl-
monophosphine-ligated palladacyclic precatalysts.