Ancillary Ligand Design in the Development of Palladium Catalysts for Challenging Selective Monoarylation Reactions - New Trends in Cross-Coupling: Theory and Applications - page 241

P

Pd

(5 mol%)

N Cl

X NH 2

+

NH 3
(3 equiv)

R

R

O

E E

NaO t Bu, 1,4-dioxane
room temperature

X = Cl, Br, I, OTs
E = N, CH

33 examples
41-99%

Figure 5.8 Broad scope in the room temperature selective monoarylation of ammo-
nia with (hetero)aryl (pseudo)halides employing (k 2 -P,N-L10)Pd(Ph)Cl as
a precatalyst.

conceivable that the direct use of this putative catalytic intermediate serves
to by-pass deleterious side reactions that may otherwise occur during cata-
lyst activation steps.

5.2.5 Summary
In less than a decade following the pioneering report of palladium-catalyzed
ammonia monoarylation by Shen and Hartwig, a number of highly effective
catalyst systems for such transformations have been identified, thereby
permitting significant practical advances. Collectively, catalysts reported to
date allow for a broad spectrum of (hetero)aryl (pseudo)halides to be ac-
commodated, including transformations that are highly chemoselective,
proceed at room temperature, and/or that can be exploited in the assembly
of synthetically important heterocyclic frameworks. Although formally be-
yond the scope of this review, it is worthy of mention that carbonylative
variants of such ammonia monoarylation reactions have also emerged that
offer a novel entry point to the construction of primary aromatic amides
from (hetero)aryl halides, carbon monoxide and ammonia. 48-51 The identi-
fication of useful catalysts for ammonia monoarylation laid the groundwork
for the development of previously unknown BHA reactions involving the
selective monoarylation of hydrazine with (hetero)aryl (pseudo)halides.

5.3 Selective Monoarylation of Hydrazine
Arylhydrazines function as important synthons in the construction of myriad
heterocyclic nitrogen-containing compounds, including most notably in-
doles via the Fischer indole synthesis. 52 Given the ubiquitous nature of such
heterocyclic frameworks in biologically active molecules, 53-56 it is under-
standable that there is considerable interest in developing ecient synthetic
routes to arylhydrazines. Conventional methods for preparing aryl-
hydrazines involve the stoichiometric oxidation of anilines to their corres-
ponding diazonium salts, followed by reduction. Alternatively, hydrazine
can in some cases react directly with electron-deficient haloarenes in