Chemistry Reference
In-Depth Information
OSiMe
3
O
OMe
PIFA
MeOH-CH
2
C
l
2
Br
Bu
3
SnH
6 ste
p
s
OMe
N
O
AIBN, PhH;
SiO
2
0°C, 15 sec
(10 g scale)
N
OMe
H
O
O
423
(72%)
422
424
(68%)
OMe
OMe
O
HO
HO
N
N
6 steps
Snider
et al
.
N
R
Me
3
SiO
HO
HO
HO
O
P
O
425
(45%)
426
(58%)
409
(R = NHMe)
427
(R = H))
SCHEME 10.68.
The Ar
1
-6 spirocyclization manifold has been exploited by Wardrop and Zhang in
their enantioselective synthesis of lactam
,
165
a pivotal intermediate in Kishi's
pioneering route to the dendrobatid alkaloid (
432
)-perhydrohistrionicotoxin (12H-
) (Scheme 10.69).
166
The quaternary stereogenic center of the 1-azaspiro
[5.5]undecane skeleton common to both
HTX;
433
433
and fasicularin
410
(Fig. 10.6) was
established in this case through diastereoselective cyclization of
428
, which provided
430
in excellent yield. As indicated, this reaction is believed to proceed through a
transition state resembling chair conformer
in which the principle control
element is the potential steric strain between the
o
-methoxyl group of the aromatic
ring and the pseudoaxial C-H bond at the
429
b
-position of the amide. After transposition
of the 2,4-cyclohexadienone ring of
to the corresponding cyclohexanone, the
formal synthesis of perhydrohistrionicotoxin (
430
433
) was completed by conversion of
431
to Kishi's lactam (
432
) through a five-step sequence. Although 1,4-cyclo-
hexadienes
435
, obtained through the Birch reduction of arenes
434
, have found
widespread use as masked
b
-oxo carbonyl synthons
436
, the possibility that 2,5-
cyclohexadienones
might also be employed to the same end has largely been
overlooked (Scheme 10.70). Taking advantage of the accessibility to such substrates
that nitrenium ion chemistry offers, Wardrop and Burge have developed a novel
strategy for the stereoselective preparation of di- and trisubstituted azetidinone,
pyrrolidinone, and piperidinone derivatives, featuring the oxidative cleavage of
spirolactams
438
(Scheme 10.71).
167
Ozonolysis of dienone
440
440
and reductive
workup with thiourea proceeded smoothly in methanol
to generate unstable
