Chemistry Reference
In-Depth Information
H
H
1.2 eq. PIFA
NH
3
O
O
O
N
MeOH
20 min
HN
OMe
1.0 eq. TFA
CH
2
Cl
2
(0.15 M)
2 h, 0°C
N
H
TFAO
OMe
H
HO
OMe
597
(not isolated)
598
(92%, d.r. > 25:1)
(70%, w/o TFA)
596
PIFA
O
O
O
p
+
OMe
OMe
N
N
I
Ph
OMe
H
N
+
σ
Ph-I
OTFA
-
CF
3
CO
2
-
599
CF
3
CO
2
600
601
596
H
+
Al
AL
1
Ph-I
>>1
PIFA
O
‡
O
O
OMe
+
O
N
Me
N
N
N
OTFA
sp
3
OMe
H
OMe
O
603
604
602
SCHEME 10.98.
to mirror that originally made by Romero, who noted that addition of TFA to the
PIFA-mediated Ar
2
-n annulation of
O
-methyl hydroxamates led to increases in
yield.
144
The acid catalysis plays a significant role in the formation of
is
also apparent from the inhibitory effect of acid scavengers and the failure of both
PhI(OAc)
2
and Pb(OAc)
4
to mediate cyclofunctionalization of
600
.
The author's current mechanistic interpretation of this remarkable transforma-
tion is outlined in Scheme 10.98 and is partly based on the observed formation
(NMR) and consumption of an intermediate tentatively assigned as
596
603
.Inthis
case, cyclization begins with ligand substitution of PIFA
116
by
596
to form amido-
,
117,118
which undergoes ligand coupling to form
N
,
N
-bisheteroa-
tom-substituted (anomeric) amide
3
-iodane
l
599
,
108
603
or fragmentation to yield singlet
nitrenium ion
600
. Intramolecular cycloaddition of this electrophile, via transition
.
214
Alternatively,
state
may
arise from
603
, through an S
N
2-like reaction, which although prohibited in conven-
tional amides, is feasible at the pyramidalized
N-
center of anomeric amides, as
seminal studies by Glover have revealed.
215
However, in light of Glover's obser-
vation that these atypical amides also undergo A
Al
1 acid-catalyzed solvolysis to
604
, would generate
601
, and subsequently
597
601
