AMMONIUM YLIDES AS BUILDING BLOCKS FOR ALKALOID SYNTHESIS - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 461

group in 269 followed by exposure to a catalytic amount of FeCl 3 produced 270 in
56%yield. Extension of the terminal alkene installed a fragment of the “western” ring.
The sulfonyl group was then replaced with another fragment that set up a ring-closing
metathesis to close the western ring. The resulting metathesis precursor 271 was
reacted with catalytic amounts of the Grubbs second generation catalyst and the
urethane was transformed into the diol portion of the eastern ring shown in 272 .
When Weinreb and coworkers published their early studies directed toward the
synthesis of the tricyclic core of sarain A, Heathcock and coworkers had been working
on a similar approach [98]. For example, aziridine 273 produced 274 in 94% yield
when heated at 350 C under vacuum (Scheme 13.53). In this example, the ethyl ester
that serves as a functional handle for construction of the eastern ring is part of the
starting material and provides a doubly stabilized azomethine ylide intermediate.
Several variations were also examined to explore the scope of this type of intramo-
lecular cyclization. Aziridines 275a-275c were subjected to flash vacuum pyrolysis to
produce compounds 276 , 277 , and 278 in 78%, 68%, and 78% yield, respectively. The
formation of 276 is significant in that no other examples of secondary amides
undergoing successful 1,3-dipolar cycloadditions were observed. Ultimately, this
aziridine fragmentation route to the tricyclic corewas abandoned in favor of a reaction
between 279 and formaldehyde in boiling toluene that gave 280 in 78% yield [99].

CO 2 Et
Bu

O

CO 2 Et

O

350 °C
FVP

Bu

N Me

N

N

N

Me O

O

94%

O

O H

273 274

O

O

CO 2 Et

O O

Bn CO 2 Et Bu

O CO 2 Et

Bu

350°C N

R 1

N

Bu N

N

EtO N

HN

Bn N

FVP

N

R 2

Bu

H

H

276 (78%) 277 (68%) 278 (78%)

275a (R 1 = H; R 2 = CH 2 CH=CH 2 )
275b (R 1 = Bn; R 2 = CH 2 CCH)
275c (R 1 = Bn; R 2 = CH 2 CH 2 CH 2 CH=CH 2 )

O CO 2 Et

CO 2 Et

N

(CH 2 O) n

H 2 N Bn

N

O

PhMe, reflux
78%

Bn N OBn

OBn

H

279 280

MeO 2 C MeO 2 C

O CH 2 OTBS

1. Swern
2. NaClO 2

1. NaBH 4
2. TFAA, Py

CO 2 Bn

Ns

N H

N

N CO 2 Bn N CO 2 Bn

O N

3. DBU
4. PhSH
K 2 CO 3

3. MeI, K 2 CO 3
4. LiHDMS, THF

CH 2 OH

H H

H

NsHN OTBS OTBS

70%

281 282 283

32%

SCHEME 13.53