Biomedical Engineering Reference
In-Depth Information
TABLE 5.16 Representative Sultam Analogs 65 Obtained from the Reaction Sequence
Shown in Scheme 5.25
R
1
R
2
Entry
Yield (%)
1
4-OMe-Bn
OH
65a
,62
2
4-OMe-Bn
Me
65b
,86
3
n
-Oct
OEt
65c
,90
4
2-OMe-Ph
OMe
65d
,78
The 2-haloanilide
68
can either be formed in situ using a copper-catalyzed cross-
coupling of a corresponding 1,2-dihaloarene
66
and a primary amide
67
(method A),
or via acylation of a 2-haloamine
70
and an acid chloride
71
(method B). The limited
commercial availability of the 1,2-dihaloarenes as well as lower regioselectivities
render the first procedure less versatile in terms of library design. While optimizing
reaction conditions, Viirre et al. found that a one-pot domino acylation/cross-coupling
approach proceeded more efficiently under microwave irradiation conditions. Reac-
tion times of 15 min in the microwave were obtained compared to 24 h under standard
heating conditions. It should be noted that the microwave irradiations were carried out
on a smaller scale and under higher dilutions due to the stirring limitations with the
insoluble base. A library of 24 analogs was constructed using four 2-bromoanilines
and six acid chlorides, and the optimized microwave conditions provided isolated
yields ranging from 21 to 97% (Figure 5.1).
5.5 RADICAL DOMINO REACTIONS
With a particular interest in exploring the synthetic utility of the high
-character
of the central C-C bond of bicyclo[1.1.0]butanes [29]
70
, Wipf and Walczak devel-
oped an
N
-allylation/Alder-ene and an
N
-allylation/formal [2
+
2] domino reaction
SCHEME 5.26
Synthesis of benzoxazoles.
