Palladium- and Copper-Catalyzed Aryl Halide Amination ...

REVIEW Palladium- and Copper-Catalyzed Heterocycle Synthesis 17
cles in good yields from either the o-iodo, o-bromo- or ochlorobenzanilides.
116 Similar cyclizations have also been
reported by Jiang and Ma 117 and Kantam and co-workers.
118
H
N
Br
N
Scheme 54
In 2009 Sun and co-workers extended this type of cyclization
to the synthesis of 2-substituted oxazolopyridines. 119
As shown in Scheme 55, a copper(I) iodide/diamine or
copper(I) iodide/phenanthroline catalyst system proved to
be optimal, yielding the desired heterocycles from the cyclization
of o-chloro- or o-bromopyridylamides, respectively.
Me
N
Scheme 55
CuI (5 mol%)
1,10-phenanthroline
(10 mol%)
O OMe Cs 2CO 3
DME, relfux
O Ph
89%
N N
O
90%
Cbz
25
H
N
CuI (5 mol%)
(10 mol%)
N
O
Cl
K2CO3 toluene, reflux
N O
91%
N
H
N
O
Br
Ph
Cl
CuI (5 mol%)
1,10-phenanthroline
(10 mol%)
Cs2CO3
THF, reflux
MeO
N
The Batey research group developed a further synthesis of
benzoxazoles involving intramolecular carbon–oxygen
bond formation. The substrates were again o-halobenzanilides;
however, these were formed in situ from the reaction
of o-bromoanilines and acyl chlorides. 70 A copper(I)
iodide/1,10-phenanthroline combination was found to be
the optimal catalyst system for this one-pot strategy. In
addition, the use of microwave irradiation gave substantially
better results than conventional heating. A library of
24 benzoxazoles was prepared, examples of which are
shown in Scheme 56.
A tandem approach to benzoxazoles was reported by
Glorius and Altenhoff, in which reaction of o-dihalobenzenes
with amides underwent copper(I) iodide/diamine
catalyzed carbon–nitrogen followed by carbon–oxygen
cross-couplings to yield the desired heterocycles. 120 Examples
of diiodo-, dibromo- and mixed dihalobenzenes,
as well as dihalopyridines (Br and Cl) were successfully
coupled to benzamide affording 2-phenylbenzoxazoles
(Scheme 57). The dibromobenzene substrate was utilized
to demonstrate variation of the amide partner, giving aryl,
Me
N
O
99%
N
O
90%
97%
N
O
Ph
Ph
Cl
Me
S
O
+
Scheme 56
alkyl, vinyl and heterocyclic 2-substituted benzoxazoles.
The use of o-bromochlorobenzenes allowed the regioselective
synthesis of substituted benzoxazoles, with the reaction
proceeding via initial amidation at the aryl bromide
position. Batey and co-workers had previously reported
on investigations of related processes, but had not
achieved an efficient system. 70
Scheme 57
Cl
O
NH 2
Br
N
3.3 Isocoumarins
CuI (10 mol%)
1,10-phenanthroline
(20 mol%)
Cs 2CO3, MeCN
210 °C, 15 min, MW
O
91%
In 1999 Shen and Wang described the synthesis of isocoumarins
from a palladium-catalyzed reaction of gem-dibromovinyl
benzoates with an organostannane. 121 For
example, reaction of benzoate 114 with phenyltrimethylstannane
using a trifurylphosphine-derived palladium catalyst
delivered isocoumarin 115 in 92% yield (Scheme
58). The tandem process is believed to proceed via an initial
Stille reaction of the ‘E’ bromide with the stannane,
which is followed by an intramolecular carbon–oxygen
bond-forming cyclization and ensuing elimination of methyl
bromide. Examples using phenyl, furyl, thienyl and
vinyl tin reagents gave the 3-substituted isocoumarins in
mostly excellent yields, and both esters and methoxy
groups could be tolerated on the aromatic ring. Willis and
co-workers reported a palladium-catalyzed carbonylative
isocoumarin synthesis, commencing from the same a-(o-
Synthesis 2011, No. 1, 1–22 © Thieme Stuttgart · New York
Me
O O Ph
F3C
O
66%
85%
Br
+
Br
O OMe
114
85% O
Scheme 58
O
H 2N Ph
Br
Br
+
PhSnMe3 O
O
CuI (5 mol%)
25 (10 mol%)
K2CO 3
toluene, 110 °C
80%
Pd2(dba)3 (2.5 mol%)
P(2-furyl)3 (15 mol%)
toluene, 100 °C
O
O
S
MeO
N
MeO
N
N
O
90%
115, 92%
81%
O
O
S
Ph
O
O
Ph
Ph