Chemistry Reference
In-Depth Information
CF
3
CO
2
OCOCF
3
PIFA
TFE, 0°C
O
Ad
E
I
O
R
Ph
N
HN
Ar
H
Ar
R
TFA
PhI, TFA
591
(R = Me, Allyl, Bn,
c
-Hex)
592
CF
3
CO
2
Basic
workup
PhI
F
3
C
O
Ar
O
O
O
N
R
N
R
N
R
Ar
O
Ar
O
PhI
593
594
595
(50-88%)
SCHEME 10.97.
ketone
(Scheme 10.96). Tempting as it might be to invoke the involvement of a
1
H
-azirinium intermediate in this process, which would arise from concerted
nitrenium ion-alkyne addition, this interpretation is inconsistent with the observed
formation of
anti-
and
syn-
addition products and is unlikely given the inherent strain
of these species. The electron-deficient alkynes (entries 9-11) that fail to undergo
cyclization is a further indication that this transformation proceeds through a vinyl
cation intermediate.
Intriguingly, Dom
ınguez and Tellitu have subsequently demonstrated that PIFA
also mediates the cyclization of
587
-alkynylamide substrates bearing
N
-alkyl rather
than
N
-aryl substituents (Scheme 10.97).
211
Since the ligand substitution of
iodine(III) reagents with
N
-alkylamides is known to generate amido-
b
3
-iodanes
but not nitrenium ions,
118
which would be insufficiently stabilized in this case, an
alternative mechanism involving iodane activation of the alkyne prior to cyclization
was posited by the authors. Although these cyclofunctionalization reactions do not
involve nitrenium ions, they are nonetheless remarkable in that capture of the puta-
tive iodane
l
results in lactam rather than lactone formation, which is
the kinetically favored outcome commonly observed in most alkene and alkyne
halofunctionalization reactions.
212
Wardrop
et al.
have investigated the intramolecular reaction of
N-
acyl-
N
-alkoxy
nitrenium ions with alkenes, generated through oxidation of
O
-alkyl hydroxa-
mates, and found this process to be a remarkably versatile method with which to
access 5, 6, 7 and 8-membered
p
-complex
592
-hydroxyalkyl lactam systems (Scheme 10.98).
213
Initial studies conducted upon cyclopentene derivative
a
revealed that exposure
of unsaturated hydroxamates to PIFA in CH
2
Cl
2
-mediated intramolecular
anti-
oxamidation to generate trifluoroacetate
596
597
, which upon
in situ
methanolysis then
cleanly provided
as a single diastereomer in excellent overall yield. Signifi-
cantly, addition of trifluoroacetic acid to the cyclization reaction was found to
accelerate this process, and also increased its efficiency. This observation appears
598
