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R
2
R
2
N
Pd(OAc)
2
(10 mol%)
BQ, CO/O
2
,NaOAc
AcOH, Room temp.
R
3
R
1
Ar
R
1
N
R
3
Ar
O
Scheme 10.77 Amine-directed C-H carbonylation.
Pd(OAc)
2
(10 mol%)
BQ (1 equiv), CO (1 atm)
p
TsOH.H
2
O(0.5equiv)
AcOH / dioxane (2:1)
60 - 80 °C, 18 - 36 h
NHCOR
NHCOR
COOH
Scheme 10.78 Oxidative carbonylation for the preparationof anthranilic acids.
Recently, Gaunt and co-workers reported the room temperature carbony-
lation of N-aryl-b-arylethylamines.
98
N-Aryl substitution using a 4-methox-
yphenyl group was anticipated to reduce the nucleophilicity of the nitrogen
atom and reduce the likelihood of bis-amino-Pd(II) complex formation that
could prevent carbopalladation and at the same time increase the acidity of
the aryl N-H bond. This approach proved successful, with the reaction being
effective at room temperature under 1 atm of CO and O
2
(Scheme 10.77).
Studies of the stoichiometric reaction of cyclopalladated complexes con-
taining primary arylalkylamines to form lactams were reported by Vicente
and co-workers.
99
As noted above for allylic substrates, the use of carboxylate as a directing
group was explored by Yu's group.
92
Optimized conditions for converting
benzoic to phthalic acids were found to be Pd(OAc)
2
as catalyst with Ag
2
CO
3
as oxidant with 2 equiv. of NaOAc in 1,4-dioxane at 130 1C under 1 atm of
CO. Significant steric and electronic effects were noted, suggestive of an
electrophilic palladation pathway. Different conditions were required to
carbonylate anilides for the formation of anthranilic acids
(Scheme 10.78).
100
Without the addition of acid (e.g. acetic, trifluoroacetic or
p-toluenesulfonic acid), the presence of CO inhibited the C-H activation
process and promoted the reduction of Pd(II) to Pd(0). A number of minor
changes to the synthetic protocol in terms of solvent and additives were
required to optimize the reaction for different substrates. The reaction could
also be carried out using benzanilides with reaction exclusively on the an-
iline fragment giving N-benzoylanthranilic acids.
Similarly, Lloyd-Jones and co-workers identified conditions for the re-
action of arylureas to form anthranilates by methoxycarbonylation.
101
Good
yields were obtained at room temperature when using Pd(OTs)
2
(MeCN)
2
as
catalyst with benzoquinone as oxidant and p-toluenesulfonic acid
(0.5 equiv.) as additive in 1 : 1 THF-MeOH under CO (1 atm). If the reaction
was carried out in CH
2
Cl
2
instead of THF-MeOH, cyclic imidates were ob-
tained (Scheme 10.79). Control experiments suggested that anthranilate
formation occurred via methanolysis of the imidate.
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