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ligand
exchange
reductive
e
limination
Pd
I
FG
C
-H activation
-HX
C
C
Pd
II
[Pd
0
]
+
L CH
Pd
II
L CFG
+
L
X
L
Oxidant
+HX
Scheme 12.1 Reductive functionalization pathway: Pd
II/0
catalytic cycle.
reductive
elimination
2e
-
oxidation
oxidant-FG
FG
C-H activation
-HX
C
C
+[Pd
II
]
Pd
II
L CH
+
Pd
IV
L CFG
Pd
II
L
L
X
ligand exchange
Scheme 12.2 Electrophilic functionalization pathway:
two-electron oxidation of
palladacycle.
transformation is achieved by using an electrophilic reagent (two-electron
oxidation process) (Scheme 12.2).
4
12.2.1 Intramolecular Direct Arylation
Pd-catalyzed intramolecular direct arylation can be traced back to 1982,
when a product of such a reaction was obtained as a side product in the Heck
coupling of ethyl acrylate with bromocinnolines (Scheme 12.3).
13
Subsequently, related five- and six-membered ring compounds were
synthesized through this approach (Scheme 12.4).
14,15
In the case of six-
membered ring compounds, dehalogenation was also observed due to the
lower nucleophilicity of simple arenes.
To overcome this problem, Rawal and co-workers used phenol-containing
substrates to obtain the corresponding cyclized product with excellent yields
and selectivity.
16
They proposed that the hydroxyl group undergoes depro-
tonation to generate a more reactive species (Scheme 12.5). Protection of the
phenolic oxygen leads to lower yields.
In this context, Echavarren and co-workers proposed a mechanism for
these palladium intramolecular-cyclization reactions,
17
which was further
supported by the theoretical calculations (Figure 12.2).
18
Fagnou's group carried out extensive investigations to understand intra-
molecular direct arylation reactions in detail.
19
Their improved reaction
conditions tolerate different functional groups and are applicable to the
formation of both six- and seven-membered rings (Scheme 12.6).
It was observed that ligand A (for a six-membered ring) and B (for a seven-
membered ring) with Pd(OAc)
2
produced excellent results for aryl bromides,
but these catalytic systems failed in the case of aryl chlorides and sur-
prisingly for aryl iodides.
20
To overcome this, the authors applied more
electron-rich NHC (C) and different alkylphosphine (D and E) ligands for the
direct arylation of aryl chlorides.
21,22
Preformed catalysts with an NHC lig-
and (C) were found slightly less active than in situ-formed catalytic species.
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