Chemistry Reference
In-Depth Information
Glover
t
-BuOCl
AgBF
4
O
O
HN
CH
2
Cl
2
O
N
PhH
Cl
N
Me
O
O
Me
O
OMe
299
301
300
Kikugawa
Ag
2
CO
3
/TFA
or
t
-BuOCl
CH
2
Cl
2
N
OMe
O
Zn(OAc)
2
MeNO
2
reflux
HN
OMe
O
Cl
N
OMe
O
303
304
(83%; 94%)
302
PhI(OTFA)
2
CH
2
Cl
2
SCHEME 10.47.
generation of
N-
acyl-
N
-alkoxy nitrenium ions through Lewis acid-catalyzed
heterolysis of
N
-halogeno-
N-
alkoxyamides, heralded the beginning of modern
synthetic nitrenium ion chemistry.
105,106
Prepared from the corresponding
O
-alkyl hydroxamates, by chlorination with
t
-butyl hypochlorite,
N-
chlorohydroxamate esters undergo inter- and intramolecular
aromatic substitution upon treatment with Lewis acids, most notably silver(I) salts
(Scheme 10.47). For example, Glover found that treatment of
N
-chlorohydroxamic
ester
300
with AgBF
4
in benzene yielded benzooxazine
301
, while Kikugawa
reported that addition of
to a solution of silver carbonate in trifluoroacetic
acid rapidly yielded dihydroquinolinone
303
. While Kikugawa's original method-
ology was hampered by use of large quantities of trifluoroacetic acid, later studies by
this group demonstrated that cyclization could also be promoted under neutral
condition, through the use of anhydrous zinc(II) acetate in refluxing nitromethane.
107
From a mechanistic standpoint, the intramolecular aromatic substitution reactions
shown in Scheme 10.47 have widely been interpreted as proceeding via stabilized
nitrenium ion intermediates, formed through the heterolysis of the substrate
nitrogen-chlorine bond. While this type of S
N
1 reactivity is improbable at the planar
nitrogen center of most carboxamides,
N-
chlorohydroxamate esters, being members
of the anomeric class of amides, are
sp
3
-hydridized at nitrogen and consequently
capable of undergoing S
N
1 and S
N
2 reactions at this position (Figure 10.4). Extensive
studies by Glover have shown that in amides that bear two heteroatoms at nitrogen,
the combined effect of these substituents markedly alters the geometry and reactivity
at this center. Most pertinent to this discussion is the pronounced anomeric effect
304
