Chemistry Reference
In-Depth Information
TABLE 10.6. Iodine(III)-Mediated Spirocyclization of O-Alkyl Arylhydroxamates.
Effect of Arene Substitution and Tether Size on Product Yield and Distribution
OMe
O
MeO
OMe
PIFA
CH
2
Cl
2
-MeOH
H
2
O
R
1
R
1
R
1
OR
2
OR
2
OR
2
HN
N
N
-78 to -15°C
1.5 h
10 min
n
n
n
O
O
O
345
346
347
R
1
R
2
Entry
n
Yield (%)
73
a
1
1
H
OMe
2
0
OMe
OMe
53
3
0
OMe
OBn
86
4
1
OMe
OMe
81
5
1
OMe
OBn
98
6
2
OMe
OMe
92
7
2
OMe
OBn
83
a
Reaction performed at 0
C for 15 s.
to access azaspirodienones on a large scale.
128
Since initial studies revealed that
cyclization under these conditions generated
347
and varying amounts of dimethyl
acetal
, water was added to the reaction mixture prior to workup in order to
hydrolyze this unwanted product. Although spirocyclization proceeds at 0
C
(Table 10.6, entry 1), less optimization with respect to reaction time was required
with the use of low temperatures. The tolerance of
O
-benzyl esters in this process
(entries 3, 5, 7) is notable not only in that it provides access to
N-
hydroxy
lactams,
129
through hydrogenolysis, but also from the standpoint that the Ag(I)-
assisted solvolysis of the corresponding
O
-benzyl
N
-chlorohydroxamates fails to
generate nitrenium ions and instead leads to benzyl cation formation.
107
While Nishiyama has found that nitrenium ions can also be generated directly from
O-
alkyl hydroxamates via electrochemical oxidation, the yields of spirocyclization
under these conditions were found to be inferior to those obtained with PIFA or PhI
(OCH
2
CF
3
)
2
, the hypervalent iodine(III) reagent purportedly generated by electrolysis
of iodobenzene in 2,2,2-trifluoroethanol (TFE) (Scheme 10.54).
130
That this reagent
actually proves to be a superior oxidant to PIFA, with regards to the formation of acid-
sensitive 2,4-cyclohexandienone
346
, is significant and likely reflects the mild
conditions under which this novel iodane is generated.
More recently, Kita has reported amildmethod for the formation of
N-
acyl-
N-
alkoxy
nitrenium ions
349
351
, using catalytic hypervalent iodine reagents generated by oxidation
with
m-
CPBA (Table 10.7).
131,132
In the presence of trifluoroethanol
(TFE), both
O
-alkyl hydroxamates and
N
-acyl-
N
-aminophthalimides
of iodotoluene
353
350
underwent
ipso
cyclization to form azaspiranes
352
in excellent yield (entries 1 & 2). The
